{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:44:39Z","timestamp":1791873879483,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T00:00:00Z","timestamp":1646784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["BX004256"],"award-info":[{"award-number":["BX004256"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["RX001141"],"award-info":[{"award-number":["RX001141"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"United States Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX005235"],"award-info":[{"award-number":["IK6BX005235"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32AI132164"],"award-info":[{"award-number":["T32AI132164"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005351","name":"Neurosurgery Research &amp; Education Foundation","doi-asserted-by":"publisher","award":["NREF 2020-21"],"award-info":[{"award-number":["NREF 2020-21"]}],"id":[{"id":"10.13039\/100005351","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Germinal matrix hemorrhage (GMH) is a devastating disease of infancy that results in intraventricular hemorrhage, post-hemorrhagic hydrocephalus (PHH), periventricular leukomalacia, and neurocognitive deficits. There are no curative treatments and limited surgical options. We developed and characterized a mouse model of GMH based on the injection of collagenase into the subventricular zone of post-natal pups and utilized the model to investigate the role of complement in PHH development. The site-targeted complement inhibitor CR2Crry, which binds deposited C3 complement activation products, localized specifically in the brain following its systemic administration after GMH. Compared to vehicle, CR2Crry treatment reduced PHH and lesion size, which was accompanied by decreased perilesional complement deposition, decreased astrocytosis and microgliosis, and the preservation of dendritic and neuronal density. Complement inhibition also improved survival and weight gain, and it improved motor performance and cognitive outcomes measured in adolescence. The progression to PHH, neuronal loss, and associated behavioral deficits was linked to the microglial phagocytosis of complement opsonized neurons, which was reversed with CR2Crry treatment. Thus, complement plays an important role in the pathological sequelae of GMH, and complement inhibition represents a novel therapeutic approach to reduce the disease progression of a condition for which there is currently no treatment outside of surgical intervention.<\/jats:p>","DOI":"10.3390\/ijms23062943","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T11:30:38Z","timestamp":1646825438000},"page":"2943","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["A Role of Complement in the Pathogenic Sequelae of Mouse Neonatal Germinal Matrix Hemorrhage"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6259-7648","authenticated-orcid":false,"given":"Mohammed","family":"Alshareef","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Medical University of South Carolina, 301 CSB, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalil","family":"Mallah","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB 204, MSC 504, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0818-0830","authenticated-orcid":false,"given":"Tyler","family":"Vasas","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Alawieh","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davis","family":"Borucki","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"},{"name":"Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Couch","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB 204, MSC 504, Charleston, SC 29425, USA"},{"name":"Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Cutrone","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2944-4380","authenticated-orcid":false,"given":"Chelsea","family":"Shope","sequence":"additional","affiliation":[{"name":"College of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramin","family":"Eskandari","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Medical University of South Carolina, 301 CSB, Charleston, SC 29425, USA"},{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB 204, MSC 504, Charleston, SC 29425, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, BSB 204, MSC 504, Charleston, SC 29425, USA"},{"name":"Ralph Johnson VA Medical Center, Charleston, SC 29401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1542\/peds.2009-2416","article-title":"Annual Summary of Vital Statistics: 2007","volume":"125","author":"Heron","year":"2010","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1542\/peds.2015-0944","article-title":"Periventricular\/Intraventricular Hemorrhage and Neurodevelopmental Outcomes: A Meta-analysis","volume":"136","author":"Mukerji","year":"2015","journal-title":"Pediatrics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3171\/2011.12.PEDS11136","article-title":"Neonatal posthemorrhagic hydrocephalus from prematurity: Pathophysiology and current treatment concepts","volume":"9","author":"Robinson","year":"2012","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1542\/peds.2013-0372","article-title":"New South Wales and Australian Capital Territory Neonatal Intensive Care Units\u2019 Data Collection. Intraventricular Hemorrhage and Neurodevelopmental Outcomes in Extreme Preterm Infants","volume":"133","author":"Bolisetty","year":"2014","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"580","DOI":"10.3171\/2014.11.PEDS14364","article-title":"Outcomes of intraventricular hemorrhage and posthemorrhagic hydrocephalus in a population-based cohort of very preterm infants born to residents of Nova Scotia from 1993 to 2010","volume":"15","author":"Radic","year":"2015","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.clp.2009.07.014","article-title":"Intracranial Hemorrhage in the Preterm Infant: Understanding It, Preventing It","volume":"36","author":"Bassan","year":"2009","journal-title":"Clin. Perinatol."},{"key":"ref_7","first-page":"112","article-title":"A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection","volume":"41","author":"Nejat","year":"2008","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.wneu.2013.01.096","article-title":"Long-Term Outcomes of Ventriculoperitoneal Shunt Surgery in Patients with Hydrocephalus","volume":"81","author":"Reddy","year":"2014","journal-title":"World Neurosurg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Das, S., Montemurro, N., Ashfaq, M., Ghosh, D., Sarker, A.C., Khan, A.H., Dey, S., and Chaurasia, B. (2022). Resolution of Papilledema Following Ventriculoperitoneal Shunt or Endoscopic Third Ventriculostomy for Obstructive Hydrocephalus: A Pilot Study. Medicina, 58.","DOI":"10.3390\/medicina58020281"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"627","DOI":"10.3171\/2017.2.PEDS16561","article-title":"Papilledema in children with hydrocephalus: Incidence and associated factors","volume":"19","author":"Lee","year":"2017","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1080\/14728222.2017.1397628","article-title":"Challenges for intraventricular hemorrhage research and emerging therapeutic targets","volume":"21","author":"Garton","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3109\/07853890.2010.481085","article-title":"Chemokine CCL18 predicts intraventricular hemorrhage in very preterm infants","volume":"42","author":"Kallankari","year":"2010","journal-title":"Ann. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12987-017-0083-0","article-title":"Chemokine and cytokine levels in the lumbar cerebrospinal fluid of preterm infants with post-hemorrhagic hydrocephalus","volume":"14","author":"Habiyaremye","year":"2017","journal-title":"Fluids Barriers CNS"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1523\/JNEUROSCI.2197-17.2018","article-title":"Identifying the Role of Complement in Triggering Neuroinflammation after Traumatic Brain Injury","volume":"38","author":"Alawieh","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/imr.12470","article-title":"Injury site-specific targeting of complement inhibitors for treating stroke","volume":"274","author":"Alawieh","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-017-0894-6","article-title":"Natural IgM antibodies that bind neoepitopes exposed as a result of spinal cord injury, drive secondary injury by activating complement","volume":"14","author":"Narang","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref_17","unstructured":"Janeway, C.A., Travers, P., and Walport, M. (2001). Immunobiology: The Immune System in Health and Disease, Garland Science. [5th ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3324\/haematol.2015.128538","article-title":"Complement inhibitors to treat IgM-mediated autoimmune hemolysis","volume":"100","author":"Wouters","year":"2015","journal-title":"Haematologica"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/S0165-0173(98)00015-0","article-title":"The role of the complement system in traumatic brain injury","volume":"27","author":"Stahel","year":"1998","journal-title":"Brain Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.brainres.2010.07.106","article-title":"A novel preclinical rodent model of collagenase-induced germinal matrix\/intraventricular hemorrhage","volume":"1356","author":"Alles","year":"2010","journal-title":"Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.expneurol.2012.04.003","article-title":"Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus","volume":"236","author":"Lekic","year":"2012","journal-title":"Exp. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1172\/JCI25208","article-title":"Targeted complement inhibition by C3d recognition ameliorates tissue injury without apparent increase in susceptibility to infection","volume":"115","author":"Atkinson","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.molimm.2018.06.005","article-title":"Tissue-targeted complement therapeutics","volume":"102","author":"Tomlinson","year":"2018","journal-title":"Mol. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8068","DOI":"10.4049\/jimmunol.181.11.8068","article-title":"A Novel Targeted Inhibitor of the Alternative Pathway of Complement and Its Therapeutic Application in Ischemia\/Reperfusion Injury","volume":"181","author":"Huang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.clp.2008.07.014","article-title":"The Diagnosis, Management, and Postnatal Prevention of Intraventricular Hemorrhage in the Preterm Neonate","volume":"35","author":"McCrea","year":"2008","journal-title":"Clin. Perinatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/jnen\/62.3.292","article-title":"Posthemorrhagic Ventricular Dilation in the Neonate: Development and Characterization of a Rat Model","volume":"62","author":"Cherian","year":"2003","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.expneurol.2005.09.010","article-title":"Persistent motor deficit following infusion of autologous blood into the periventricular region of neonatal rats","volume":"197","author":"Balasubramaniam","year":"2006","journal-title":"Exp. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain development in rodents and humans: Identifying benchmarks of maturation and vulnerability to injury across species","volume":"106\u2013107","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1590\/S0102-67202012000100011","article-title":"Rat\u2019s age versus human\u2019s age: What is the relationship?","volume":"25","author":"Andreollo","year":"2012","journal-title":"Arq. Bras. Cir. Dig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-3-7091-0693-8_10","article-title":"A Novel Preclinical Model of Germinal Matrix Hemorrhage Using Neonatal Rats","volume":"111","author":"Lekic","year":"2011","journal-title":"Acta Neurochir. Suppl."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1126\/scitranslmed.aao6459","article-title":"Targeted complement inhibition salvages stressed neurons and inhibits neuroinflammation after stroke in mice","volume":"10","author":"Alawieh","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4042","DOI":"10.1523\/JNEUROSCI.2462-19.2020","article-title":"Complement-Dependent Synaptic Uptake and Cognitive Decline after Stroke and Reperfusion Therapy","volume":"40","author":"Alawieh","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1227\/NEU.0000000000000524","article-title":"Role of Hemoglobin and Iron in Hydrocephalus After Neonatal Intraventricular Hemorrhage","volume":"75","author":"Strahle","year":"2014","journal-title":"Neurosurgurey"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/jcbfm.2014.56","article-title":"Role of Red Blood Cell Lysis and Iron in Hydrocephalus after Intraventricular Hemorrhage","volume":"34","author":"Gao","year":"2014","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/nm.4361","article-title":"Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus","volume":"23","author":"Karimy","year":"2017","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1111\/cns.13144","article-title":"Secukinumab attenuates reactive astrogliosis via IL-17RA\/(C\/EBPbeta)\/SIRT1 pathway in a rat model of germinal matrix hemorrhage","volume":"25","author":"Liu","year":"2019","journal-title":"CNS Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"113003","DOI":"10.1016\/j.expneurol.2019.113003","article-title":"Astrogliosis inhibition attenuates hydrocephalus by increasing cerebrospinal fluid reabsorption through the glymphatic system after germinal matrix hemorrhage","volume":"320","author":"Ding","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"E8","DOI":"10.3171\/2012.1.FOCUS11366","article-title":"Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage\u2013induced secondary brain injury and as potential targets for intervention","volume":"32","author":"Babu","year":"2012","journal-title":"Neurosurg. Focus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.it.2010.01.002","article-title":"Crosstalk pathways between Toll-like receptors and the complement system","volume":"31","author":"Hajishengallis","year":"2010","journal-title":"Trends Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1038\/s41573-019-0031-6","article-title":"Clinical promise of next-generation complement therapeutics","volume":"18","author":"Mastellos","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.nurt.2010.07.002","article-title":"Role of microglia in neurotrauma","volume":"7","author":"Loane","year":"2010","journal-title":"Neurotherapeutics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1177\/1073858405278321","article-title":"Reactive Astrocytes in Neural Repair and Protection","volume":"11","author":"Sofroniew","year":"2005","journal-title":"Neuroscientist"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.bja.2017.11.096","article-title":"Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice","volume":"120","author":"Hu","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1542\/peds.111.4.759","article-title":"Phase 1 Trial of Prevention of Hydrocephalus After Intraventricular Hemorrhage in Newborn Infants by Drainage, Irrigation, and Fibrinolytic Therapy","volume":"111","author":"Whitelaw","year":"2003","journal-title":"Pediatrics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.brainresbull.2019.08.013","article-title":"Inhibition of neuronal ferroptosis in the acute phase of intracerebral hemorrhage shows long-term cerebroprotective effects","volume":"153","author":"Chen","year":"2019","journal-title":"Brain Res. Bull."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Leinhase, I., Holers, V.M., Thurman, J.M., Harhausen, D., Schmidt, O.I., Pietzcker, M., Taha, M.E., Rittirsch, D., Huber-Lang, M., and Smith, W.R. (2006). Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation. BMC Neurosci., 7.","DOI":"10.1186\/1471-2202-7-55"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3171\/2017.1.PEDS16496","article-title":"Hydrocephalus Clinical Research, N. Shunting outcomes in posthemorrhagic hydrocephalus: Results of a Hydrocephalus Clinical Research Network prospective cohort study","volume":"20","author":"Wellons","year":"2017","journal-title":"J. Neurosurg. Pediatr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1097\/00006123-199711000-00015","article-title":"Outcome for Preterm Infants with Germinal Matrix Hemorrhage and Progressive Hydrocephalus","volume":"41","author":"Levy","year":"1997","journal-title":"Neurosurgery"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1182\/blood.V126.23.2137.2137","article-title":"Safety and Pharmacokinetics of the Complement Inhibitor TT30 in a Phase I Trial for Untreated PNH Patients","volume":"126","author":"Risitano","year":"2015","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.molimm.2019.07.030","article-title":"Compendium of current complement therapeutics","volume":"114","author":"Zelek","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bbr.2013.11.010","article-title":"The effect of brief neonatal cryoanesthesia on physical development and adult cognitive function in mice","volume":"259","author":"Janus","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref_52","first-page":"e51194","article-title":"Barnes Maze Testing Strategies with Small and Large Rodent Models","volume":"84","author":"Rosenfeld","year":"2014","journal-title":"J. Vis. Exp."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.physbeh.2010.02.025","article-title":"Influence of intracerebral administration of NO agents in dorsal hippocampus (CA1) on cannabinoid state-dependent memory in the step-down passive avoidance test","volume":"100","author":"Nasehi","year":"2010","journal-title":"Physiol. Behav."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13104-018-3374-x","article-title":"Combined CatWalk Index: An improved method to measure mouse motor function using the automated gait analysis system","volume":"11","author":"Crowley","year":"2018","journal-title":"BMC Res. Notes"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jneumeth.2004.04.029","article-title":"Infarct volume quantification in mouse focal cerebral ischemia: A comparison of triphenyltetrazolium chloride and cresyl violet staining techniques","volume":"139","author":"Vemuganti","year":"2004","journal-title":"J. Neurosci. Methods"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jneumeth.2005.01.006","article-title":"Free-D: An integrated environment for three-dimensional reconstruction from serial sections","volume":"145","author":"Andrey","year":"2005","journal-title":"J. Neurosci. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/tpj.13189","article-title":"Strategy and software for the statistical spatial analysis of 3D intra-cellular distributions","volume":"87","author":"Biot","year":"2016","journal-title":"Plant J."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2943\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:29Z","timestamp":1760135609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/6\/2943"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,9]]},"references-count":57,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23062943"],"URL":"https:\/\/doi.org\/10.3390\/ijms23062943","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,9]]}}}