{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:49:05Z","timestamp":1785206945090,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T00:00:00Z","timestamp":1664323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Neurological Disease and Stroke in the National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS096143"],"award-info":[{"award-number":["R01NS096143"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Traumatic brain injury (TBI) is a major leading cause of death and disability. While previous studies regarding focal pathologies following TBI have been done, there is a lack of information concerning the role of analgesics and their influences on injury pathology. Buprenorphine (Bup), an opioid analgesic, is a commonly used analgesic in experimental TBI models. Our previous studies investigated the acute effects of Buprenorphine-sustained release-Lab (Bup-SR-Lab) on diffuse neuronal\/glial pathology, neuroinflammation, cell damage, and systemic physiology. The current study investigated the longer-term chronic outcomes of Bup-SR-Lab treatment at 4 weeks following TBI utilizing a central fluid percussion injury (cFPI) model in adult male rats. Histological assessments of physiological changes, neuronal damage, cortical and thalamic cytokine expression, microglial and astrocyte morphological changes, and myelin alterations were done, as we had done in our acute study. In the current study the Whisker Nuisance Task (WNT) was also performed pre- and 4w post-injury to assess changes in somatosensory sensitivity following saline or Bup-SR-Lab treatment. Bup-SR-Lab treatment had no impact on overall physiology or neuronal damage at 4w post-injury regardless of region or injury, nor did it have any significant effects on somatosensory sensitivity. However, greater IL-4 cytokine expression with Bup-SR-Lab treatment was observed compared to saline treated animals. Microglia and astrocytes also demonstrated region-specific morphological alterations associated with Bup-SR-Lab treatment, in which cortical microglia and thalamic astrocytes were particularly vulnerable to Bup-mediated changes. There were discernable injury-specific and region-specific differences regarding myelin integrity and changes in specific myelin basic protein (MBP) isoform expression following Bup-SR-Lab treatment. This study indicates that use of Bup-SR-Lab could impact TBI-induced glial alterations in a region-specific manner 4w following diffuse brain injury.<\/jats:p>","DOI":"10.3390\/pharmaceutics14102068","type":"journal-article","created":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T22:53:19Z","timestamp":1664405599000},"page":"2068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Post-Injury Buprenorphine Administration Is Associated with Long-Term Region-Specific Glial Alterations in Rats"],"prefix":"10.3390","volume":"14","author":[{"given":"Jane","family":"Ryu","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pantea","family":"Jeizan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saira","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sareena","family":"Ehsan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7925-3910","authenticated-orcid":false,"given":"Jefin","family":"Jose","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Regan","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Gorse","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrina","family":"Kelliher","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-2228","authenticated-orcid":false,"given":"Audrey","family":"Lafrenaye","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, VA 23298, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,28]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Surveillance for traumatic brain injury-related deaths\u2014United States, 1997\u20132007","volume":"60","author":"Coronado","year":"2011","journal-title":"Morb. Mortal. Wkly. Rep. Surveill. Summ."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/01.WCB.0000111614.19196.04","article-title":"Pathophysiology of cerebral ischemia and brain trauma: Similarities and differences","volume":"24","author":"Bramlett","year":"2004","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_3","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_4","first-page":"67","article-title":"Epidemiological trends of traumatic brain and spinal cord injury in Puerto Rico from November 10th, 2006, through May 24th, 2011","volume":"37","author":"Brau","year":"2018","journal-title":"Puerto. Rico. Health Sci. J."},{"key":"ref_5","unstructured":"Center-TBI (2022, August 10). Traumatic Brain Injury Fact sheFets and Policy Brief. Available online: https:\/\/www.center-tbi.eu\/files\/news\/21571f81-20b8-4860-a3dd-1f6e27d02b3d.pdf."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.mcn.2015.03.001","article-title":"Epidemiology of mild traumatic brain injury and neurodegenerative disease","volume":"66","author":"Gardner","year":"2015","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000502580","article-title":"A Nationwide Study of Incidence and Mortality Due to Traumatic Brain Injury in Ecuador (2004\u20132016)","volume":"54","author":"Mascialino","year":"2020","journal-title":"Neuroepidemiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1080\/02699050801938975","article-title":"Traumatic brain injury in Finland 1991-2005: A nationwide register study of hospitalized and fatal TBI","volume":"22","author":"Koskinen","year":"2008","journal-title":"Brain Inj."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0079-6123(06)61009-1","article-title":"Progressive damage after brain and spinal cord injury: Pathomechanisms and treatment strategies","volume":"161","author":"Bramlett","year":"2007","journal-title":"Prog. Brain Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/neu.2015.3965","article-title":"The Role of Thalamic Damage in Mild Traumatic Brain Injury","volume":"33","author":"Grossman","year":"2016","journal-title":"J. Neurotrauma"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1212\/WNL.0b013e3181cff5d5","article-title":"Thalamic integrity underlies executive dysfunction in traumatic brain injury","volume":"74","author":"Little","year":"2010","journal-title":"Neurology"},{"key":"ref_12","unstructured":"National Research Council (2011). Guide Laboratory Animals for the Care and Use of Eighth Edition Committee for the Update of the Guide for the Care and Use of Laboratory Animals Institute for Laboratory Animal Research Division on Earth and Life Studies, The National Academies Press. National Research Council of the National Academies."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Murphy, A., Barbaro, J., Mart\u00ednez-Aguado, P., Chilunda, V., Jaureguiberry-Bravo, M., and Berman, J.W. (2019). The Effects of Opioids on HIV Neuropathogenesis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02445"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1016\/0024-3205(81)90529-4","article-title":"Buprenorphine: Characteristics of binding sites in the rat central nervous system","volume":"29","author":"Villiger","year":"1981","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1093\/bja\/57.2.192","article-title":"Clinical Actions of Fentanyl and Buprenorphine the Significance of Receptor Binding","volume":"57","author":"Boas","year":"1985","journal-title":"Br. J. Anaesth."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1037\/a0013628","article-title":"Opioids and the Treatment of Chronic Pain: Controversies, Current Status, and Future Directions","volume":"16","author":"Rosenblum","year":"2008","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"81","DOI":"10.30802\/AALAS-JAALAS-21-000081","article-title":"Extended-release Buprenorphine, an FDA-indexed Analgesic, Attenuates Mechanical Hypersensitivity in Rats (Rattus norvegicus)","volume":"61","author":"Alamaw","year":"2022","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Blaney, A., Jampachaisri, K., Huss, M.K., and Pacharinsak, C. (2021). Sustained release buprenorphine effectively attenuates postoperative hypersensitivity in an incisional pain model in neonatal rats (Rattus norvegicus). PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246213"},{"key":"ref_19","first-page":"387","article-title":"Pharmacokinetic comparison of sustained-release and standard buprenorphine in mice","volume":"53","author":"Clark","year":"2014","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_20","first-page":"193","article-title":"Antinociceptive effects of sustained-release buprenorphine in a model of incisional pain in rats (Rattus norvegicus)","volume":"53","author":"Chum","year":"2014","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.2460\/ajvr.78.3.321","article-title":"Pharmacokinetics and pharmacodynamics of buprenorphine and sustained-release buprenorphine after administration to adult alpacas","volume":"78","author":"Dooley","year":"2017","journal-title":"Am. J. Vet. Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ryu, J., Stone, P., Lee, S., Payne, B., Gorse, K., and Lafrenaye, A. (2021). Buprenorphine alters microglia and astrocytes acutely following diffuse traumatic brain injury. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-88030-z"},{"key":"ref_23","first-page":"1769","article-title":"The ARRIVE Guidelines 2.0: Updated Guidelines for Reporting Animal Research","volume":"49","author":"Hurst","year":"2020","journal-title":"PLoS Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1038\/jcbfm.2014.122","article-title":"Moderately elevated intracranial pressure after diffuse traumatic brain injury is associated with exacerbated neuronal pathology and behavioral morbidity in the rat","volume":"34","author":"Lafrenaye","year":"2014","journal-title":"J. Cereb. Blood Flow Metab. Off. J. Int. Soc. Cereb. Blood Flow Metab."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Hernandez, M.L., Marone, M., Gorse, K.M., and Lafrenaye, A.D. (2022). Cathepsin B Relocalization in Late Membrane Disrupted Neurons Following Diffuse Brain Injury in Rats. ASN Neuro, 14.","DOI":"10.1177\/17590914221099112"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3171\/jns.1987.67.1.0110","article-title":"A fluid percussion model of experimental brain injury in the rat","volume":"67","author":"Dixon","year":"1987","journal-title":"J. Neurosurg."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hernandez, M.L., Chatlos, T., Gorse, K.M., and Lafrenaye, A.D. (2019). Neuronal Membrane Disruption Occurs Late Following Diffuse Brain Trauma in Rats and Involves a Subpopulation of NeuN Negative Cortical Neurons. Front. Neurol., 10.","DOI":"10.3389\/fneur.2019.01238"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1089\/neu.2009.1237","article-title":"The whisker nuisance task identifies a late-onset, persistent sensory sensitivity in diffuse brain-injured rats","volume":"27","author":"McNamara","year":"2010","journal-title":"J. Neurotrauma"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.bbr.2011.09.016","article-title":"Comparison of rat sensory behavioral tasks to detect somatosensory morbidity after diffuse brain-injury","volume":"226","author":"Learoyd","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/neu.2011.2091","article-title":"Hypersensitive glutamate signaling correlates with the development of late-onset behavioral morbidity in diffuse brain-injured circuitry","volume":"29","author":"Thomas","year":"2012","journal-title":"J. Neurotrauma"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Krishna, G., Bromberg, C., Connell1, E.C., Mian, E., Hu, C., Lifshitz, J., Adelson, P.D., and Thomas, T.C. (2020). Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission. Front. Neurol., 11.","DOI":"10.3389\/fneur.2020.00749"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1089\/neu.2008.0523","article-title":"Spinal cord contusion causes acute plasma membrane damage","volume":"26","author":"Simon","year":"2009","journal-title":"J. Neurotrauma"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Gorse, K.M., and Lafrenaye, A.D. (2018). The importance of inter-species variation in traumatic brain injury-induced alterations of microglial-axonal interactions. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00778"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lafrenaye, A.D., Todani, M., Walker, S.A., and Povlishock, J.T. (2015). Microglia processes associate with diffusely injured axons following mild traumatic brain injury in the micro pig. J. Neuro inflamm., 12.","DOI":"10.1186\/s12974-015-0405-6"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1097\/NEN.0b013e3181588245","article-title":"Neuroinflammatory responses after experimental diffuse traumatic brain injury","volume":"66","author":"Kelley","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/01.jnen.0000248558.75950.4d","article-title":"Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death","volume":"66","author":"Lifshitz","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1002\/glia.23523","article-title":"Traumatic brain injury-induced neuronal damage in the somatosensory cortex causes formation of rod-shaped microglia that promote astrogliosis and persistent neuroinflammation","volume":"66","author":"Witcher","year":"2018","journal-title":"Glia"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1038\/jcbfm.2012.95","article-title":"Increased intracranial pressure after diffuse traumatic brain injury exacerbates neuronal somatic membrane poration but not axonal injury: Evidence for primary intracranial pressure-induced neuronal perturbation","volume":"32","author":"Lafrenaye","year":"2012","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Byrnes, K.R., Loane, D.J., Stoica, B.A., Zhang, J., and Faden, A.I. (2012). Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury. J. Neuroinflamm., 9.","DOI":"10.1186\/1742-2094-9-43"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/ame2.12157","article-title":"Lipid bound extended release buprenorphine (high and low doses) and sustained release buprenorphine effectively attenuate post-operative hypersensitivity in an incisional pain model in mice (Mus musculus)","volume":"4","author":"Navarro","year":"2021","journal-title":"Anim. Model Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hamood, Y., Abdullah, M., Ghoul, H.E., Saad, N., Dysko, R.C., and Zhang, Z. (2022). Sex specific effects of buprenorphine on behavior, astrocytic opioid receptor expression and neuroinflammation after pediatric traumatic brain injury in mice. Brain Behav. Immun. Health, 22.","DOI":"10.1016\/j.bbih.2022.100469"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.clinbiomech.2018.05.016","article-title":"Mechanoporation is a potential indicator of tissue strain and subsequent degeneration following experimental traumatic brain injury","volume":"64","author":"LaPlaca","year":"2019","journal-title":"Clin. Biomech."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.expneurol.2017.01.004","article-title":"Rapid neuroinflammatory response localized to injured neurons after diffuse traumatic brain injury in swine","volume":"290","author":"Wofford","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1523\/JNEUROSCI.5103-10.2011","article-title":"Diffuse traumatic axonal injury in the mouse induces atrophy, c-Jun activation, and axonal outgrowth in the axotomized neuronal population","volume":"31","author":"Greer","year":"2011","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.neuroscience.2022.03.020","article-title":"Defining the Role of Anti- and Pro-inflammatory Outcomes of Interleukin-6 in Mental Health","volume":"492","year":"2022","journal-title":"Neuroscience"},{"key":"ref_47","first-page":"32","article-title":"Changes of interleukin-1 beta, tumor necrosis factor alpha and interleukin-6 in brain and plasma after brain injury in rats","volume":"7","author":"Zhu","year":"2004","journal-title":"Chin. J. Traumatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/1744806916647055","article-title":"Diffuse traumatic brain injury induces prolonged immune dysregulation and potentiates hyperalgesia following a peripheral immune challenge","volume":"12","author":"Rowe","year":"2016","journal-title":"Mol. Pain"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/pr.2017.83","article-title":"Sex and age differences in phenylephrine mechanisms and outcomes after piglet brain injury","volume":"82","author":"Curvello","year":"2017","journal-title":"Pediatr. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chen, L., Zhu, L., Lu, D., Wu, Z., Han, Y., Xu, P., Chang, L., and Wu, Q. (2020). Interleukin 4 Affects Epilepsy by Regulating Glial Cells: Potential and Possible Mechanism. Front. Mol. Neurosci., 13.","DOI":"10.3389\/fnmol.2020.554547"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4213","DOI":"10.4049\/jimmunol.1202246","article-title":"Interleukin-4: A Cytokine to Remember","volume":"189","author":"Gadani","year":"2012","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1684\/ecn.2017.0392","article-title":"Buprenorphine differentially affects M1- and M2-polarized macrophages from human umbilical cord blood","volume":"28","author":"Sun","year":"2017","journal-title":"Eur. Cytokine Netw."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s10616-022-00534-2","article-title":"The secretome of microglia induced by IL-4 of IFN-\u03b3 differently regulate proliferation, differentiation and survival of adult neural stem\/progenitor cell by targeting the PI3K-Akt pathway","volume":"74","author":"Jiang","year":"2022","journal-title":"Cytotechnology"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Xu, Y., Zhi, F., Peng, Y., Mao, J., Balboni, G., Yang, Y., and Xia, Y. (2022). A Critical Role of \u03b4-Opioid Receptor in Anti-microglial Activation Under Stress. Front. Aging Neurosci., 14.","DOI":"10.3389\/fnagi.2022.847386"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Vicario, N., Denaro, S., Turnaturi, R., Longhitano, L., Spitale, F.M., Spoto, S., Marrazzo, A., Zappal\u00e0, A., Tibullo, D., and Volti, G.L. (2022). Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23115864"},{"key":"ref_56","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_57","doi-asserted-by":"crossref","unstructured":"Ziebell, J.M., Taylor, S.E., Cao, T., Harrison, J.L., and Lifshitz, J. (2012). Rod microglia: Elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury. J. Neuro inflamm., 9.","DOI":"10.1186\/1742-2094-9-247"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pestana, F., Edwards-Faret, G., Belgard, T.G., Martirosyan, A., and Holt, M.G. (2020). No Longer Underappreciated: The Emerging Concept of Astrocyte Heterogeneity in Neuroscience. Brain Sci., 10.","DOI":"10.3390\/brainsci10030168"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Farhy-Tselnicker, I., Boisvert, M.M., Liu, H., Dowling, C., Erikson, G.A., Blanco-Suarez, E., Farhy, C., Shokhirev, M.N., Ecker, J., and Allen, N.J. (2021). Activity-Dependent Modulation of Synapse-Regulating Genes in Astrocytes. eLife, 10.","DOI":"10.7554\/eLife.70514"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1002\/cne.25261","article-title":"Development of astrocyte morphology and function in mouse visual thalamus","volume":"530","author":"Somaiya","year":"2022","journal-title":"J. Comp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41593-020-0602-1","article-title":"Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map","volume":"23","author":"Bayraktar","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/mp.2015.65","article-title":"Glial fibrillary acidic protein is differentially expressed across cortical and subcortical regions in healthy brains and downregulated in the thalamus and caudate nucleus of depressed suicides","volume":"21","author":"Nagy","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jneuroim.2019.04.004","article-title":"Clinical characteristics of autoimmune GFAP astrocytopathy","volume":"332","author":"Kimura","year":"2019","journal-title":"J. Neuroimmunol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Lin, C.-H., Tao, P.-L., Tsay, H.-J., Chiang, Y.-C., Chang, W.-T., Ho, I.K., and Shie, F.-S. (2021). Dextromethorphan Dampens Neonatal Astrocyte Activation and Endoplasmic Reticulum Stress Induced by Prenatal Exposure to Buprenorphine. Behav. Neurol., 2021.","DOI":"10.1155\/2021\/6301458"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"\u00dc\u00e7eyler, N., Topuzo\u01e7lu, T., Schie\u00dfer, P., Hahnenkamp, S., and Sommer, C. (2011). IL-4 deficiency is associated with mechanical hypersensitivity in mice. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028205"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Reiss, D., Maurin, H., Audouard, E., Mart\u00ednez-Navarro, M., Xue, Y., Herault, Y., Maldonado, R., Caba\u00f1ero, D., and Gaveriaux-Ruff, C. (2021). Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice. Front. Cell Neurosci., 15.","DOI":"10.3389\/fncel.2021.745178"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1084\/jem.20141656","article-title":"Serge Rivest Inefficient clearance of myelin debris by microglia impairs remyelinating processes","volume":"212","author":"Lampron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_68","first-page":"218","article-title":"Components of Myelin Damage and Repair in the Progression of White Matter Pathology After Mild Traumatic","volume":"74","author":"Mierzwa","year":"2015","journal-title":"Brain Inj."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/bs.vh.2019.05.004","article-title":"Kappa opioid receptor and oligodendrocyte remyelination","volume":"111","author":"Wang","year":"2019","journal-title":"Vitam. Horm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1111\/j.1471-4159.2006.03882.x","article-title":"Extensive degradation of myelin basic protein isoforms by calpain following traumatic brain injury","volume":"98","author":"Liu","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1111\/jnc.12195","article-title":"Myelin management by the 18.5\u2013kDa and 21.5\u2013kDa classic myelin basic protein isoforms","volume":"125","author":"Harauz","year":"2013","journal-title":"J. Neurochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1093\/jnen\/nlw025","article-title":"Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells","volume":"75","author":"Flygt","year":"2016","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Dent, K.A., Christie, K.J., Bye, N., Basrai, H.S., Turbic, A., Habgood, M., Cate, H.S., and Turnley, A.M. (2015). Oligodendrocyte Birth and Death following Traumatic Brain Injury in Adult Mice. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121541"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"661","DOI":"10.30802\/AALAS-JAALAS-21-000028","article-title":"Serum Buprenorphine Concentrations and Behavioral Activity in Mice After a Single Subcutaneous Injection of Simbadol, Buprenorphine SR-LAB, or Standard Buprenorphine","volume":"60","author":"Myers","year":"2021","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1124\/jpet.112.201145","article-title":"Parallel Buprenorphine phMRI Responses in Conscious Rodents and Healthy Human Subjects","volume":"345","author":"Becerra","year":"2013","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s00429-014-0717-9","article-title":"A mu\u2013delta opioid receptor brain atlas reveals neuronal co-occurrence in subcortical networks","volume":"220","author":"Erbs","year":"2015","journal-title":"Brain Struct. Funct."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Shafiei, F., Afarinesh, M.R., Golshan, F., Haghpanah, T., Sabzalizadeh, M., Zangiabadi, I., and Sheibani, V. (2019). Comparison of pre-pulse inhibition, tactile discrimination learning and barrel cortical neural response in adult male rats following chronic exposure to morphine, methadone and buprenorphine. Physiol. Behav., 212.","DOI":"10.1016\/j.physbeh.2019.112694"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/10\/2068\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:41:14Z","timestamp":1760143274000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/10\/2068"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,28]]},"references-count":77,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["pharmaceutics14102068"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14102068","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202208.0244.v1","asserted-by":"object"}]},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,28]]}}}