{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:42:40Z","timestamp":1788385360760,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Adelaide Beacon of Enlightenment scholarship"},{"name":"NeuroSurgical Research Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Traumatic brain injury (TBI) is associated with an increased risk of developing Parkinson\u2019s disease (PD), though the exact mechanisms remain unclear. TBI triggers acute neuroinflammation and catecholamine dysfunction post-injury, both implicated in PD pathophysiology. The long-term impact on these pathways following TBI, however, remains uncertain. In this study, male Sprague-Dawley rats underwent sham surgery or Marmarou\u2019s impact acceleration model to induce varying TBI severities: single mild TBI (mTBI), repetitive mild TBI (rmTBI), or moderate\u2013severe TBI (msTBI). At 12 months post-injury, astrocyte reactivity (GFAP) and microglial levels (IBA1) were assessed in the striatum (STR), substantia nigra (SN), and prefrontal cortex (PFC) using immunohistochemistry. Key enzymes and receptors involved in catecholaminergic transmission were measured via Western blot within the same regions. Minimal changes in these markers were observed, regardless of initial injury severity. Following mTBI, elevated protein levels of dopamine D1 receptors (DRD1) were noted in the PFC, while msTBI resulted in increased alpha-2A adrenoceptors (ADRA2A) in the STR and decreased dopamine beta-hydroxylase (D\u03b2H) in the SN. Neuroinflammatory changes were subtle, with a reduced number of GFAP+ cells in the SN following msTBI. However, considering the potential for neurodegenerative outcomes to manifest decades after injury, longer post-injury intervals may be necessary to observe PD-relevant alterations within these systems.<\/jats:p>","DOI":"10.3390\/molecules29071470","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:05:33Z","timestamp":1711451133000},"page":"1470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Long-Term Impact of Diffuse Traumatic Brain Injury on Neuroinflammation and Catecholaminergic Signaling: Potential Relevance for Parkinson\u2019s Disease Risk"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1181-7791","authenticated-orcid":false,"given":"Ing Chee","family":"Wee","sequence":"first","affiliation":[{"name":"Cognition, Ageing and Neurodegenerative Disease Laboratory, School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0993-5622","authenticated-orcid":false,"given":"Alina","family":"Arulsamy","sequence":"additional","affiliation":[{"name":"Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway 47500, Selangor Darul Ehsan, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6150-8893","authenticated-orcid":false,"given":"Frances","family":"Corrigan","sequence":"additional","affiliation":[{"name":"Head Injury Lab, School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4380-7600","authenticated-orcid":false,"given":"Lyndsey","family":"Collins-Praino","sequence":"additional","affiliation":[{"name":"Cognition, Ageing and Neurodegenerative Disease Laboratory, School of Biomedicine, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.3171\/2017.10.JNS17352","article-title":"Estimating the Global Incidence of Traumatic Brain Injury","volume":"130","author":"Dewan","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6609a1","article-title":"Traumatic Brain Injury\u2013Related Emergency Department Visits, Hospitalizations, and Deaths\u2014United States, 2007 and 2013","volume":"66","author":"Taylor","year":"2017","journal-title":"MMWR Surveill. Summ."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Faul, M., Wald, M.M., Xu, L., and Coronado, V.G. (2010). Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalization and Deaths 2002\u20132006. Cent. Dis. Control Prev. Natl. Cent. Inj. Prev. Control, Available online: https:\/\/stacks.cdc.gov\/view\/cdc\/5571.","DOI":"10.15620\/cdc.5571"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1474-4422(18)30415-0","article-title":"Global, Regional, and National Burden of Traumatic Brain Injury and Spinal Cord Injury, 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016","volume":"18","author":"James","year":"2019","journal-title":"Lancet Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1474-4422(12)70262-4","article-title":"Incidence of Traumatic Brain Injury in New Zealand: A Population-Based Study","volume":"12","author":"Feigin","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic Brain Injury and Risk of Neurodegenerative Disorder","volume":"91","author":"Brett","year":"2022","journal-title":"Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/ana.24396","article-title":"Traumatic Brain Injury in Later Life Increases Risk for Parkinson Disease: TBI Increases Risk for PD","volume":"77","author":"Gardner","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of Brain Pathology Related to Sporadic Parkinson\u2019s Disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s Disease: Mechanisms and Models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S1353-8020(98)00012-1","article-title":"Distribution of Noradrenaline and Dopamine (3-Hydroxytyramine) in the Human Brain and Their Behavior in Diseases of the Extrapyramidal System","volume":"4","author":"Ehringer","year":"1998","journal-title":"Park. Relat. Disord."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10571-018-0632-3","article-title":"Dopamine: Functions, Signaling, and Association with Neurological Diseases","volume":"39","author":"Klein","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2970","DOI":"10.1093\/brain\/awp209","article-title":"Longitudinal Progression of Sporadic Parkinson\u2019s Disease: A Multi-Tracer Positron Emission Tomography Study","volume":"132","author":"Nandhagopal","year":"2009","journal-title":"Brain"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1136\/jnnp.62.2.133","article-title":"[123I]FP-CIT SPECT Shows a Pronounced Decline of Striatal Dopamine Transporter Labelling in Early and Advanced Parkinson\u2019s Disease","volume":"62","author":"Booij","year":"1997","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1007\/s00259-011-1976-9","article-title":"Predictive Value of Dopamine Transporter SPECT Imaging with [123I]PE2I in Patients with Subtle Parkinsonian Symptoms","volume":"39","author":"Ziebell","year":"2012","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1056\/NEJM198804073181402","article-title":"Uneven Pattern of Dopamine Loss in the Striatum of Patients with Idiopathic Parkinson\u2019s Disease","volume":"318","author":"Kish","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","article-title":"Ageing and parkinson\u2019s disease: Substantia nigra regional selectivity","volume":"114","author":"Fearnley","year":"1991","journal-title":"Brain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41593-022-01061-1","article-title":"Single-Cell Genomic Profiling of Human Dopamine Neurons Identifies a Population That Selectively Degenerates in Parkinson\u2019s Disease","volume":"25","author":"Kamath","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/0022-510X(95)00316-T","article-title":"Differences in the Reduced 18F-Dopa Uptakes of the Caudate and the Putamen in Parkinson\u2019s Disease: Correlations with the Three Main Symptoms","volume":"136","author":"Otsuka","year":"1996","journal-title":"J. Neurol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1136\/jnnp.67.6.737","article-title":"Usefulness of a Dopamine Transporter PET Ligand [18F]Beta-CFT in Assessing Disability in Parkinson\u2019s Disease","volume":"67","author":"Rinne","year":"1999","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1001\/archneur.60.3.337","article-title":"Neuronal Loss Is Greater in the Locus Coeruleus Than Nucleus Basalis and Substantia Nigra in Alzheimer and Parkinson Diseases","volume":"60","author":"Zarow","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neulet.2013.02.012","article-title":"Changes in Substantia Nigra and Locus Coeruleus in Patients with Early-Stage Parkinson\u2019s Disease Using Neuromelanin-Sensitive MR Imaging","volume":"541","author":"Ohtsuka","year":"2013","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/mds.27785","article-title":"The Locus Coeruleus: Another Vulnerability Target in Parkinson\u2019s Disease","volume":"34","author":"Oertel","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/ejn.13435","article-title":"Dopamine and Noradrenaline, but Not Serotonin, in the Human Claustrum Are Greatly Reduced in Patients with Parkinson\u2019s Disease: Possible Functional Implications","volume":"45","author":"Sitte","year":"2017","journal-title":"Eur. J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s004010000247","article-title":"\u03b1-Synuclein Immunopositive Parkinson\u2019s Disease-Related Inclusion Bodies in Lower Brain Stem Nuclei","volume":"101","author":"Braak","year":"2001","journal-title":"Acta Neuropathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1212\/01.wnl.0000183056.89590.0d","article-title":"Excessive Daytime Sleepiness and Subsequent Development of Parkinson Disease","volume":"65","author":"Abbott","year":"2005","journal-title":"Neurology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.expneurol.2017.04.006","article-title":"Role of the Locus Coeruleus Catecholaminergic Neurons in the Chemosensory Control of Breathing in a Parkinson\u2019s Disease Model","volume":"293","author":"Oliveira","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102873","DOI":"10.1016\/j.nicl.2021.102873","article-title":"Locus Coeruleus Degeneration Is Associated with Disorganized Functional Topology in Parkinson\u2019s Disease","volume":"32","author":"Zhou","year":"2021","journal-title":"NeuroImage Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1016\/j.neurobiolaging.2008.01.001","article-title":"Microglial Responses to Dopamine in a Cell Culture Model of Parkinson\u2019s Disease","volume":"30","author":"Mastroeni","year":"2009","journal-title":"Neurobiol. Aging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1161\/STROKEAHA.115.009792","article-title":"Activation of Dopamine D2 Receptor Suppresses Neuroinflammation through \u03b1B-Crystalline by Inhibition of NF-\u03baB Nuclear Translocation in Experimental ICH Mice Model","volume":"46","author":"Zhang","year":"2015","journal-title":"Stroke"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s12974-017-1039-7","article-title":"Activation of Dopamine D1 Receptor Decreased NLRP3-Mediated Inflammation in Intracerebral Hemorrhage Mice","volume":"15","author":"Wang","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1111\/j.1471-4159.2009.06189.x","article-title":"Relationship between Microglial Activation and Dopaminergic Neuronal Loss in the Substantia Nigra: A Time Course Study in a 6-Hydroxydopamine Model of Parkinson\u2019s Disease","volume":"110","author":"Sadeghian","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature11748","article-title":"Suppression of Neuroinflammation by Astrocytic Dopamine D2 Receptors via \u03b1B-Crystallin","volume":"494","author":"Shao","year":"2013","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.mcn.2005.01.003","article-title":"Dopamine and Noradrenaline Control Distinct Functions in Rodent Microglial Cells","volume":"29","author":"Pannasch","year":"2005","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1030609","DOI":"10.3389\/fphar.2022.1030609","article-title":"Selective Vulnerability of the Locus Coeruleus Noradrenergic System and Its Role in Modulation of Neuroinflammation, Cognition, and Neurodegeneration","volume":"13","author":"Evans","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/7854_2014_356","article-title":"Neuroinflammation in Parkinson\u2019s Disease Animal Models: A Cell Stress Response or a Step in Neurodegeneration?","volume":"Volume 22","author":"Nguyen","year":"2014","journal-title":"Behavioral Neurobiology of Huntington\u2019s Disease and Parkinson\u2019s Disease"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"860","DOI":"10.3389\/fneur.2018.00860","article-title":"Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson\u2019s Disease","volume":"9","author":"Parra","year":"2018","journal-title":"Front. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.bbi.2020.01.003","article-title":"Locus Coeruleus Neurons Are Most Sensitive to Chronic Neuroinflammation-Induced Neurodegeneration","volume":"87","author":"Wang","year":"2020","journal-title":"Brain. Behav. Immun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, T.-F., Wu, S.-Y., Pan, B.-S., Tsai, S.-F., and Kuo, Y.-M. (2022). Inhibition of Nigral Microglial Activation Reduces Age-Related Loss of Dopaminergic Neurons and Motor Deficits. Cells, 11.","DOI":"10.3390\/cells11030481"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1212\/WNL.38.8.1285","article-title":"Reactive Microglia Are Positive for HLA-DR in the Substantia Nigra of Parkinson\u2019s and Alzheimer\u2019s Disease Brains","volume":"38","author":"McGeer","year":"1988","journal-title":"Neurology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/0304-3940(94)90746-3","article-title":"Tumor Necrosis Factor-\u03b1 (TNF-\u03b1) Increases Both in the Brain and in the Cerebrospinal Fluid from Parkinsonian Patients","volume":"165","author":"Mogi","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0304-3940(94)90508-8","article-title":"Interleukin-1\u03b2, Interleukin-6, Epidermal Growth Factor and Transforming Growth Factor-\u03b1 Are Elevated in the Brain from Parkinsonian Patients","volume":"180","author":"Mogi","year":"1994","journal-title":"Neurosci. Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0304-3940(96)12706-3","article-title":"Interleukin (IL)-1\u03b2, IL-2, IL-4, IL-6 and Transforming Growth Factor-\u03b1 Levels Are Elevated in Ventricular Cerebrospinal Fluid in Juvenile Parkinsonism and Parkinson\u2019s Disease","volume":"211","author":"Mogi","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3389\/fnins.2018.00626","article-title":"\u03b1-Synuclein and Noradrenergic Modulation of Immune Cells in Parkinson\u2019s Disease Pathogenesis","volume":"12","author":"Butkovich","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0306-4522(89)90247-9","article-title":"Traumatic Brain Injury in the Rat: Characterization of a Lateral Fluid-Percussion Model","volume":"28","author":"McIntosh","year":"1989","journal-title":"Neuroscience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/j.1471-4159.1979.tb11710.x","article-title":"Effect of concussive head injury on central catecholamine levels and synthesis rates in rat brain regions","volume":"33","author":"Huger","year":"1979","journal-title":"J. Neurochem."},{"key":"ref_46","first-page":"119","article-title":"Targeting Dopamine in Acute Traumatic Brain Injury","volume":"2","author":"Bales","year":"2010","journal-title":"Open Drug Discov. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s007010170138","article-title":"Alterations of Norepinephrine Levels in Plasma and CSF of Patients after Traumatic Brain Injury in Relation to Disruption of the Blood-Brain Barrier","volume":"143","author":"Mautes","year":"2001","journal-title":"Acta Neurochir."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.expneurol.2011.12.003","article-title":"Substantia Nigra Vulnerability after a Single Moderate Diffuse Brain Injury in the Rat","volume":"234","author":"Thomas","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1471-4159.2005.03382.x","article-title":"Controlled Cortical Impact Injury Affects Dopaminergic Transmission in the Rat Striatum","volume":"95","author":"Wagner","year":"2005","journal-title":"J. Neurochem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"196837","DOI":"10.3389\/fnins.2016.00458","article-title":"Traumatic Brain Injury Leads to Development of Parkinson\u2019s Disease Related Pathology in Mice","volume":"10","author":"Impellizzeri","year":"2016","journal-title":"Front. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0006-8993(95)00032-L","article-title":"Widespread and Lateralized Effects of Acute Traumatic Brain Injury on Norepinephrine Turnover in the Rat Brain","volume":"674","author":"Levin","year":"1995","journal-title":"Brain Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1179\/016164103101201094","article-title":"The Morphological and Neurochemical Effects of Diffuse Brain Injury on Rat Central Noradrenergic System","volume":"25","author":"Fujinaka","year":"2003","journal-title":"Neurol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1007\/s002590000308","article-title":"Impaired Dopaminergic Neurotransmission in Patients with Traumatic Brain Injury: A SPET Study Using 123I-\u03b2-CIT and 123I-IBZM","volume":"27","author":"Donnemiller","year":"2000","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"R80","DOI":"10.1186\/cc6931","article-title":"In Vitro Norepinephrine Significantly Activates Isolated Platelets from Healthy Volunteers and Critically Ill Patients Following Severe Traumatic Brain Injury","volume":"12","author":"Tschuor","year":"2008","journal-title":"Crit. Care"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.injury.2020.07.054","article-title":"In Adult Patients with Severe Traumatic Brain Injury, Does the Use of Norepinephrine for Augmenting Cerebral Perfusion Pressure Improve Neurological Outcome? A Systematic Review","volume":"51","author":"Spencer","year":"2020","journal-title":"Injury"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0006-8993(98)00524-1","article-title":"Norepinephrine and Traumatic Brain Injury: A Possible Role in Post-Traumatic Edema","volume":"800","author":"Hassanain","year":"1998","journal-title":"Brain Res."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Chien, Y.J., Chien, Y.C., Liu, C.T., Wu, H.C., Chang, C.Y., and Wu, M.Y. (2019). Effects of Methylphenidate on Cognitive Function in Adults with Traumatic Brain Injury: A Meta-Analysis. Brain Sci., 9.","DOI":"10.3390\/brainsci9110291"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1093\/brain\/aws322","article-title":"Inflammation and White Matter Degeneration Persist for Years after a Single Traumatic Brain Injury","volume":"136","author":"Johnson","year":"2013","journal-title":"Brain"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1097\/NEN.0000000000000021","article-title":"Progressive Neurodegeneration after Experimental Brain Trauma: Association with Chronic Microglial Activation","volume":"73","author":"Loane","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12974-019-1624-z","article-title":"Blast Traumatic Brain Injury and Serum Inflammatory Cytokines: A Repeated Measures Case-Control Study among U.S. Military Service Members","volume":"17","author":"Rusiecki","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1038\/s41598-023-32351-8","article-title":"Medial Prefrontal Cortex Oxytocin Mitigates Epilepsy and Cognitive Impairments Induced by Traumatic Brain Injury through Reducing Neuroinflammation in Mice","volume":"13","author":"Chen","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1089\/neu.2015.4361","article-title":"Pioglitazone Attenuates Neuroinflammation and Promotes Dopaminergic Neuronal Survival in the Nigrostriatal System of Rats after Diffuse Brain Injury","volume":"34","author":"Liu","year":"2017","journal-title":"J. Neurotrauma"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Acosta, S.A., Tajiri, N., Shinozuka, K., Ishikawa, H., Grimmig, B., Diamond, D., Sanberg, P.R., Bickford, P.C., Kaneko, Y., and Borlongan, C.V. (2013). Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model. PLoS ONE, 8.","DOI":"10.1371\/annotation\/a04a7468-d105-42f3-ba47-263ea2864681"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/ana.22455","article-title":"Inflammation after Trauma: Microglial Activation and Traumatic Brain Injury","volume":"70","author":"Ramlackhansingh","year":"2011","journal-title":"Ann. Neurol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1089\/neu.2010.1723","article-title":"Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat","volume":"28","author":"Hutson","year":"2011","journal-title":"J. Neurotrauma"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1089\/neu.2007.0377","article-title":"Prolonged Microgliosis in the Rhesus Monkey Central Nervous System after Traumatic Brain Injury","volume":"24","author":"McNeal","year":"2007","journal-title":"J. Neurotrauma"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ana.24064","article-title":"Chronic Neuropathological and Neurobehavioral Changes in a Repetitive Mild Traumatic Brain Injury Model: Chronic Effects of r-mTBI","volume":"75","author":"Mouzon","year":"2014","journal-title":"Ann. Neurol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/acn3.510","article-title":"Lifelong Behavioral and Neuropathological Consequences of Repetitive Mild Traumatic Brain Injury","volume":"5","author":"Mouzon","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1146\/annurev.bi.40.070171.002341","article-title":"Biochemistry of Catecholamines","volume":"40","author":"Molinoff","year":"1971","journal-title":"Annu. Rev. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2010.12.017","article-title":"Tyrosine Hydroxylase and Regulation of Dopamine Synthesis","volume":"508","author":"Daubner","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1161\/01.RES.28.3.307","article-title":"Serum Dopamine-Beta-Hydroxylase Activity","volume":"28","author":"Weinshilboum","year":"1971","journal-title":"Circ. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/0888-7543(92)90316-K","article-title":"Chromosomal Mapping of the Human Catechol-O-Methyltransferase Gene to 22q11.1\u2192q11.2","volume":"12","author":"Grossman","year":"1992","journal-title":"Genomics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bbr.2019.02.045","article-title":"Cognitive and Neuropsychiatric Impairments Vary as a Function of Injury Severity at 12 Months Post-Experimental Diffuse Traumatic Brain Injury: Implications for Dementia Development","volume":"365","author":"Arulsamy","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"111912","DOI":"10.1016\/j.bbr.2019.111912","article-title":"Age, but Not Severity of Injury, Mediates Decline in Executive Function: Validation of the Rodent Touchscreen Paradigm for Preclinical Models of Traumatic Brain Injury","volume":"368","author":"Arulsamy","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_75","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age with Human\u2019s","volume":"4","author":"Sengupta","year":"2013","journal-title":"Int. J. Prev. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/mds.24996","article-title":"Identifying Prodromal Parkinson\u2019s Disease: Pre-Motor Disorders in Parkinson\u2019s Disease","volume":"27","author":"Postuma","year":"2012","journal-title":"Mov. Disord."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"291","DOI":"10.3171\/jns.1994.80.2.0291","article-title":"A New Model of Diffuse Brain Injury in Rats. Part I: Pathophysiology and Biomechanics","volume":"80","author":"Marmarou","year":"1994","journal-title":"J. Neurosurg."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nrn3407","article-title":"Animal Models of Traumatic Brain Injury","volume":"14","author":"Xiong","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbr.2018.04.009","article-title":"Evaluation of Early Chronic Functional Outcomes and Their Relationship to Pre-Frontal Cortex and Hippocampal Pathology Following Moderate-Severe Traumatic Brain Injury","volume":"348","author":"Arulsamy","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1089\/neur.2022.0057","article-title":"Initial Severity of Injury Has Little Effect on the Temporal Profile of Long-Term Deficits in Locomotion, Anxiety, and Cognitive Function after Diffuse Traumatic Brain Injury","volume":"4","author":"Corrigan","year":"2023","journal-title":"Neurotrauma Rep."},{"key":"ref_81","unstructured":"Paxinos, G., and Watson, C. (2006). The Rat Brain in Stereotaxic Coordinates: Hard Cover Edition, Elsevier."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s40478-020-00924-7","article-title":"Biological Links between Traumatic Brain Injury and Parkinson\u2019s Disease","volume":"8","author":"Delic","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1212\/01.WNL.0000068008.78394.2C","article-title":"Head Trauma Preceding PD: A Case-Control Study","volume":"60","author":"Bower","year":"2003","journal-title":"Neurology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e1771","DOI":"10.1212\/WNL.0000000000005522","article-title":"Mild TBI and Risk of Parkinson Disease: A Chronic Effects of Neurotrauma Consortium Study","volume":"90","author":"Gardner","year":"2018","journal-title":"Neurology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/jnc.14893","article-title":"Dopamine Beta-hydroxylase and Its Genetic Variants in Human Health and Disease","volume":"152","author":"Vrana","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1056\/NEJM198606053142307","article-title":"Isolated Failure of Autonomic Noradrenergic Neurotransmission","volume":"314","author":"Robertson","year":"1986","journal-title":"N. Engl. J. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0006-8993(77)90378-X","article-title":"Ascending Projections of the Locus Coeruleus in the Rat. II. Autoradiographic Study","volume":"127","author":"Jones","year":"1977","journal-title":"Brain Res."},{"key":"ref_88","first-page":"44P","article-title":"Neurochemical and Electrophysiological Evidence for a Projection from the Locus Coeruleus to the Substantia Nigra [Proceedings]","volume":"290","author":"Collingridge","year":"1979","journal-title":"J. Physiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s12974-019-1632-z","article-title":"Stress-Induced Microglial Activation Occurs through \u03b2-Adrenergic Receptor: Noradrenaline as a Key Neurotransmitter in Microglial Activation","volume":"16","author":"Sugama","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_90","first-page":"101","article-title":"Distribution of Dopamine-Immunoreactive Cell Bodies in the Guinea-Pig Brain","volume":"3","author":"Smits","year":"1990","journal-title":"J. Chem. Neuroanat."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/978-1-0716-2217-9_4","article-title":"Absolute Quantification of Plasma Membrane Receptors Via Quantitative Flow Cytometry","volume":"2475","author":"Fang","year":"2022","journal-title":"Methods Mol. Biol. Clifton NJ"},{"key":"ref_92","unstructured":"Wassall, R.D., Teramoto, N., and Cunnane, T.C. (2009). Encyclopedia of Neuroscience, Elsevier."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1097\/00004714-200104000-00015","article-title":"Comparing Guanfacine and Dextroamphetamine for the Treatment of Adult Attention-Deficit\/Hyperactivity Disorder","volume":"21","author":"Taylor","year":"2001","journal-title":"J. Clin. Psychopharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0893-133X(00)00111-1","article-title":"The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task","volume":"23","author":"Avery","year":"2000","journal-title":"Neuropsychopharmacology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4287","DOI":"10.1523\/JNEUROSCI.08-11-04287.1988","article-title":"The Alpha-2 Adrenergic Agonist Guanfacine Improves Memory in Aged Monkeys without Sedative or Hypotensive Side Effects: Evidence for Alpha-2 Receptor Subtypes","volume":"8","author":"Arnsten","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/0163-1047(92)90327-Z","article-title":"Effects of Medetomidine, an \u03b1-2 Adrenoceptor Agonist, and Atipamezole, an \u03b1-2 Antagonist, on Spatial Memory Performance in Adult and Aged Rats","volume":"58","author":"Carlson","year":"1992","journal-title":"Behav. Neural Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0091-3057(96)00111-6","article-title":"Medetomidine, Atipamezole, and Guanfacine in Delayed Response Performance of Aged Monkeys","volume":"55","author":"Linnankoski","year":"1996","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1097\/01.wnn.0000213919.95266.0d","article-title":"The Effect of \u03b1-2 Adrenergic Agonists on Memory and Cognitive Flexibility","volume":"19","author":"Choi","year":"2006","journal-title":"Cogn. Behav. Neurol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S0893-133X(98)00127-4","article-title":"Guanfacine, but Not Clonidine, Improves Planning and Working Memory Performance in Humans","volume":"20","year":"1999","journal-title":"Neuropsychopharmacology"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Sysoev, Y.I., Prikhodko, V.A., Chernyakov, R.T., Idiyatullin, R.D., Musienko, P.E., and Okovityi, S.V. (2021). Effects of Alpha-2 Adrenergic Agonist Mafedine on Brain Electrical Activity in Rats after Traumatic Brain Injury. Brain Sci., 11.","DOI":"10.3390\/brainsci11080981"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1038\/s41598-018-23003-3","article-title":"Neuroprotective Effect of Dexmedetomidine in a Murine Model of Traumatic Brain Injury","volume":"8","author":"Wu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_102","first-page":"107","article-title":"Alpha-2 Adrenergic Challenge with Guanfacine One Month after Mild Traumatic Brain Injury: Altered Working Memory and BOLD Response","volume":"82","author":"McAllister","year":"2011","journal-title":"Int. J. Psychophysiol. Off. J. Int. Organ. Psychophysiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S0163-1047(05)80034-2","article-title":"Delayed-Response Deficit Induced by Local Injection of the A2-Adrenergic Antagonist Yohimbine into the Dorsolateral Prefrontal Cortex in Young Adult Monkeys","volume":"62","author":"Li","year":"1994","journal-title":"Behav. Neural Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0361-9230(96)00026-3","article-title":"The Effects of Prefrontal Intracortical Microinjections of an Alpha-2 Agonist, Alpha-2 Antagonist and Lidocaine on the Delayed Alternation Performance of Aged Rats","volume":"40","author":"Tanila","year":"1996","journal-title":"Brain Res. Bull."},{"key":"ref_105","first-page":"80","article-title":"The Effects of Locus Coeruleus and Norepinephrine in Methamphetamine Toxicity","volume":"11","author":"Ferrucci","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.1016\/S1471-1931(00)00023-9","article-title":"Anatomy of the Dopamine System in the Basal Ganglia","volume":"23","author":"Smith","year":"2000","journal-title":"Trends Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Grueschow, M., Kleim, B., and Ruff, C.C. (2022). Functional Coupling of the Locus Coeruleus Is Linked to Successful Cognitive Control. Brain Sci., 12.","DOI":"10.3390\/brainsci12030305"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1152\/jn.1997.77.2.863","article-title":"Heterogeneity of Electrically Evoked Dopamine Release and Reuptake in Substantia Nigra, Ventral Tegmental Area, and Striatum","volume":"77","author":"Cragg","year":"1997","journal-title":"J. Neurophysiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1111\/j.1471-4159.1990.tb04599.x","article-title":"Blockade of the Noradrenaline Carrier Increases Extracellular Dopamine Concentrations in the Prefrontal Cortex: Evidence That Dopamine Is Taken up In Vivo by Noradrenergic Terminals","volume":"55","author":"Carboni","year":"1990","journal-title":"J. Neurochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"104551","DOI":"10.1016\/j.neuint.2019.104551","article-title":"Noradrenaline Is Crucial for the Substantia Nigra Dopaminergic Cell Maintenance","volume":"131","author":"Barkander","year":"2019","journal-title":"Neurochem. Int."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.neurobiolaging.2019.09.014","article-title":"The Noradrenergic System Is Necessary for Survival of Vulnerable Midbrain Dopaminergic Neurons: Implications for Development and Parkinson\u2019s Disease","volume":"85","author":"Hassani","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1001\/archneur.63.12.1724","article-title":"Inverse Relationship Between Brain Noradrenaline Level and Dopamine Loss in Parkinson Disease: A Possible Neuroprotective Role for Noradrenaline","volume":"63","author":"Tong","year":"2006","journal-title":"Arch. Neurol."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Isaias, I.U., Marotta, G., Pezzoli, G., Sabri, O., Schwarz, J., Crenna, P., Classen, J., and Cavallari, P. (2011). Enhanced Catecholamine Transporter Binding in the Locus Coeruleus of Patients with Early Parkinson Disease. BMC Neurol., 11.","DOI":"10.1186\/1471-2377-11-88"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3389\/fnsys.2011.00031","article-title":"Noradrenaline and Parkinson\u2019s Disease","volume":"5","author":"Delaville","year":"2011","journal-title":"Front. Syst. Neurosci."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1212\/01.wnl.0000312279.49272.9f","article-title":"Invited Article: Nervous System Pathology in Sporadic Parkinson Disease","volume":"70","author":"Braak","year":"2008","journal-title":"Neurology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/nprot.2007.44","article-title":"The Use of the Elevated plus Maze as an Assay of Anxiety-Related Behavior in Rodents","volume":"2","author":"Walf","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1089\/neu.2015.3977","article-title":"Performance of Male and Female C57BL\/6J Mice on Motor and Cognitive Tasks Commonly Used in Pre-Clinical Traumatic Brain Injury Research","volume":"33","author":"Tucker","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.pbb.2013.04.001","article-title":"Short and Long-Term Motor and Behavioral Effects of Diazoxide and Dimethyl Sulfoxide Administration in the Mouse after Traumatic Brain Injury","volume":"108","author":"Budinich","year":"2013","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1089\/neu.2018.5731","article-title":"Repeated Mild Head Injury Leads to Wide-Ranging Deficits in Higher-Order Cognitive Functions Associated with the Prefrontal Cortex","volume":"35","author":"Nolan","year":"2018","journal-title":"J. Neurotrauma"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.bbr.2011.06.012","article-title":"A Single Mild Fluid Percussion Injury Induces Short-Term Behavioral and Neuropathological Changes in the Long\u2013Evans Rat: Support for an Animal Model of Concussion","volume":"224","author":"Shultz","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41467-018-08168-9","article-title":"Optogenetic Stimulation of Medial Prefrontal Cortex Drd1 Neurons Produces Rapid and Long-Lasting Antidepressant Effects","volume":"10","author":"Hare","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s40345-020-00212-2","article-title":"Prefrontal Dopamine D1 Receptor Manipulation Influences Anxiety Behavior and Induces Neuroinflammation within the Hippocampus","volume":"9","author":"Beyer","year":"2021","journal-title":"Int. J. Bipolar Disord."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"837810","DOI":"10.3389\/fphar.2022.837810","article-title":"Dopamine Homeostasis Imbalance and Dopamine Receptors-Mediated AC\/cAMP\/PKA Pathway Activation Are Involved in Aconitine-Induced Neurological Impairment in Zebrafish and SH-SY5Y Cells","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Jones-Tabah, J., Martin, R.D., Chen, J.J., Tanny, J.C., Clarke, P.B.S., and H\u00e9bert, T.E. (2021). Dopamine D1 Receptor Activation and cAMP\/PKA Signalling Mediate Brd4 Recruitment to Chromatin to Regulate Gene Expression in Rat Striatal Neurons. Neuroscience.","DOI":"10.1101\/2021.07.01.450754"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"83","DOI":"10.3389\/fendo.2016.00083","article-title":"Protein Kinase A and Anxiety-Related Behaviors: A Mini-Review","volume":"7","author":"Keil","year":"2016","journal-title":"Front. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.yhbeh.2014.05.003","article-title":"Tonic Modulation of Anxiety-like Behavior by Corticotropin-Releasing Factor (CRF) Type 1 Receptor (CRF1) within the Medial Prefrontal Cortex (mPFC) in Male Mice: Role of Protein Kinase A (PKA)","volume":"66","author":"Miguel","year":"2014","journal-title":"Horm. Behav."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1097\/HTR.0000000000000162","article-title":"Influence of Catechol-O-Methyltransferase on Executive Functioning Longitudinally after Early Childhood Traumatic Brain Injury: Preliminary Findings","volume":"31","author":"Kurowski","year":"2016","journal-title":"J. Head Trauma Rehabil."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/00008571-199606000-00007","article-title":"Human Catechol-O-Methyltransferase Pharmacogenetics: Description of a Functional Polymorphism and Its Potential Application to Neuropsychiatric Disorders","volume":"6","author":"Lachman","year":"1996","journal-title":"Pharmacogenet. Genom."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4202","DOI":"10.1021\/bi00013a008","article-title":"Kinetics of Human Soluble and Membrane-Bound Catechol O-Methyltransferase: A Revised Mechanism and Description of the Thermolabile Variant of the Enzyme","volume":"34","author":"Lotta","year":"1995","journal-title":"Biochemistry"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.parkreldis.2018.02.015","article-title":"Catechol-O-Methyltransferase (COMT) Genetic Variants Are Associated with Cognitive Decline in Patients with Parkinson\u2019s Disease","volume":"50","author":"Lin","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"644","DOI":"10.3389\/fgene.2019.00644","article-title":"Meta-Analysis of the Effects of the Catechol-O-Methyltransferase Val158\/108Met Polymorphism on Parkinson\u2019s Disease Susceptibility and Cognitive Dysfunction","volume":"10","author":"Tang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1176\/jnp.17.4.465","article-title":"Association of COMT Val158Met Genotype with Executive Functioning Following Traumatic Brain Injury","volume":"17","author":"Lipsky","year":"2005","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.neulet.2006.11.060","article-title":"Traumatic Brain Injury Stimulates Hippocampal Catechol-O-Methyl Transferase Expression in Microglia","volume":"413","author":"Redell","year":"2007","journal-title":"Neurosci. Lett."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"819","DOI":"10.4103\/1673-5374.232529","article-title":"Dexmedetomidine Attenuates Traumatic Brain Injury: Action Pathway and Mechanisms","volume":"13","author":"Wang","year":"2018","journal-title":"Neural Regen. Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"15291","DOI":"10.1074\/jbc.M113.458901","article-title":"Norepinephrine Modulates the Motility of Resting and Activated Microglia via Different Adrenergic Receptors","volume":"288","author":"Gyoneva","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"997786","DOI":"10.3389\/fimmu.2022.997786","article-title":"Microglia Morphophysiological Diversity and Its Implications for the CNS","volume":"13","author":"Radford","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.1523\/JNEUROSCI.4363-08.2009","article-title":"Resting Microglia Directly Monitor the Functional State of Synapses In Vivo and Determine the Fate of Ischemic Terminals","volume":"29","author":"Wake","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","article-title":"Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing","volume":"101","author":"Li","year":"2019","journal-title":"Neuron"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Kenkhuis, B., Somarakis, A., Kleindouwel, L.R.T., Van Roon-Mom, W.M.C., H\u00f6llt, T., and Van Der Weerd, L. (2022). Co-Expression Patterns of Microglia Markers Iba1, TMEM119 and P2RY12 in Alzheimer\u2019s Disease. Neurobiol. Dis., 167.","DOI":"10.1016\/j.nbd.2022.105684"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"281","DOI":"10.31887\/DCNS.2009.11.3\/mbelanger","article-title":"The Role of Astroglia in Neuroprotection","volume":"11","author":"Magistretti","year":"2009","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1093\/brain\/awl165","article-title":"Essential Protective Roles of Reactive Astrocytes in Traumatic Brain Injury","volume":"129","author":"Myer","year":"2006","journal-title":"Brain"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1111\/bph.13125","article-title":"The Contribution of Astrocytes and Microglia to Traumatic Brain Injury","volume":"173","author":"Karve","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Valles, S.L., Singh, S.K., Campos-Campos, J., Colmena, C., Campo-Palacio, I., Alvarez-Gamez, K., Caballero, O., and Jorda, A. (2023). Functions of Astrocytes under Normal Conditions and after a Brain Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098434"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.arr.2014.01.004","article-title":"Ageing and Parkinson\u2019s Disease: Why Is Advancing Age the Biggest Risk Factor?","volume":"14","author":"Reeve","year":"2014","journal-title":"Ageing Res. Rev."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1159\/000156474","article-title":"Neuroinflammation Associated with Aging Sensitizes the Brain to the Effects of Infection or Stress","volume":"15","author":"Sparkman","year":"2008","journal-title":"Neuroimmunomodulation"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"10160","DOI":"10.1073\/pnas.1804641115","article-title":"Dedifferentiation of Caudate Functional Connectivity and Striatal Dopamine Transporter Density Predict Memory Change in Normal Aging","volume":"115","author":"Rieckmann","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/s43587-023-00469-z","article-title":"The Integrity of Dopaminergic and Noradrenergic Brain Regions Is Associated with Different Aspects of Late-Life Memory Performance","volume":"3","author":"Dahl","year":"2023","journal-title":"Nat. Aging"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.semcdb.2021.05.013","article-title":"Noradrenaline in the Aging Brain: Promoting Cognitive Reserve or Accelerating Alzheimer\u2019s Disease?","volume":"116","author":"Mather","year":"2021","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1016\/j.celrep.2018.08.001","article-title":"Transcriptional and Translational Differences of Microglia from Male and Female Brains","volume":"24","author":"Guneykaya","year":"2018","journal-title":"Cell Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12974-021-02124-z","article-title":"Uncovering Sex Differences of Rodent Microglia","volume":"18","author":"Han","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Santos-Galindo, M., Acaz-Fonseca, E., Bellini, M.J., and Garcia-Segura, L.M. (2011). Sex Differences in the Inflammatory Response of Primary Astrocytes to Lipopolysaccharide. Biol. Sex Differ., 2.","DOI":"10.1186\/2042-6410-2-7"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.yhbeh.2009.06.002","article-title":"Independent Influences of Sex Steroids of Systemic and Central Origin in a Rat Model of Parkinson\u2019s Disease: A Contribution to Sex-Specific Neuroprotection by Estrogens","volume":"57","author":"Gillies","year":"2010","journal-title":"Horm. Behav."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.neuroscience.2014.05.033","article-title":"Sex-Dependent Diversity in Ventral Tegmental Dopaminergic Neurons and Developmental Programing: A Molecular, Cellular and Behavioral Analysis","volume":"282","author":"Gillies","year":"2014","journal-title":"Neuroscience"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.yfrne.2014.02.002","article-title":"Sex Differences in Parkinson\u2019s Disease","volume":"35","author":"Gillies","year":"2014","journal-title":"Front. Neuroendocrinol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1212\/WNL.55.9.1358","article-title":"Parkinson\u2019s Disease and Parkinsonism in a Longitudinal Study: Two-Fold Higher Incidence in Men","volume":"55","author":"Baldereschi","year":"2000","journal-title":"Neurology"},{"key":"ref_156","first-page":"501","article-title":"Parkinson\u2019s Disease in Women and Men: What\u2019s the Difference?","volume":"9","author":"Cerri","year":"2019","journal-title":"J. Park. Dis."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/7\/1470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:49Z","timestamp":1760105929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/7\/1470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,26]]},"references-count":156,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["molecules29071470"],"URL":"https:\/\/doi.org\/10.3390\/molecules29071470","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,26]]}}}