{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:18:26Z","timestamp":1792448306280,"version":"4.5.0"},"reference-count":41,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JNS"],"published-print":{"date-parts":[[2010,12]]},"abstract":"\nObject<\/jats:title>\nTraumatic brain injury (TBI) induces significant neurological damage, including deficits in learning and memory, which contribute to a poor clinical prognosis. Treatment options to limit cognitive decline and promote neurological recovery are lacking, in part due to a poor understanding of the secondary or delayed processes that contribute to brain injury. In the present study, the authors characterized the temporal and spatial changes in the expression of postsynaptic density protein-95 (PSD-95), a key scaffolding protein implicated in excitatory synaptic signaling, after controlled cortical impacts in mice. Neurological injury, as assessed by the open-field activity test and the novel object recognition test, was compared with changes in PSD-95 expression.<\/jats:p><\/jats:sec>\n\nMethods<\/jats:title>\nAdult male CD-1 mice were subjected to controlled cortical impacts to simulate moderate TBI in humans. The spatial and temporal expression of PSD-95 was analyzed in the cerebral cortex and hippocampus at various time points following injury and sham operations. Neurological assessments were performed to compare changes in PSD-95 with cognitive deficits.<\/jats:p><\/jats:sec>\n\nResults<\/jats:title>\nA significant decrease in PSD-95 expression was observed in the ipsilateral hippocampus beginning on Day 7 postinjury. The loss of PSD-95 corresponded with a concomitant reduction in immunoreactivity for NeuN (neuronal nuclei), a neuron-specific marker. Aside from the contused cortex, a significant loss of PSD-95 immunoreactivity was not observed in the cerebral cortex. The delayed loss of hippocampal PSD-95 directly correlated with the onset of behavioral deficits, suggesting a possible causative role for PSD-95 in behavioral abnormalities following head trauma.<\/jats:p><\/jats:sec>\n\nConclusions<\/jats:title>\nA delayed loss of hippocampal synapses was observed following head trauma in mice. These data may suggest a cellular mechanism to explain the delayed learning and memory deficits in humans after TBI and provide a potential framework for further testing to implicate PSD-95 as a clinically relevant therapeutic target.<\/jats:p><\/jats:sec>","DOI":"10.3171\/2010.3.jns091212","type":"journal-article","created":{"date-parts":[[2010,4,16]],"date-time":"2010-04-16T14:06:13Z","timestamp":1271426773000},"page":"1195-1201","source":"Crossref","is-referenced-by-count":90,"title":["Delayed reduction in hippocampal postsynaptic density protein-95 expression temporally correlates with cognitive dysfunction following controlled cortical impact in mice"],"prefix":"10.3171","volume":"113","author":[{"given":"Chandramohan","family":"Wakade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Sukumari-Ramesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa D.","family":"Laird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishnan M.","family":"Dhandapani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Vender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"key":"b1-jns091212","series-title":"J Neurotrauma","first-page":"513","article-title":"A time course of contusion-induced oxidative stress and synaptic proteins in cortex in a rat model of TBI","volume":"25","author":"Ansari","year":"2008"},{"key":"b2-jns091212","series-title":"J Head Trauma Rehabil","first-page":"139","article-title":"A comparison of cognitive functioning in older adults with and without traumatic brain injury","volume":"23","author":"Ashman","year":"2008"},{"key":"b3-jns091212","series-title":"Brain Res","first-page":"195","article-title":"Hippocampally dependent and independent chronic spatial navigational deficits following parasagittal fluid percussion brain injury in the rat","volume":"762","author":"Bramlett","year":"1997"},{"key":"b4-jns091212","series-title":"Proc Natl Acad Sci U S A","first-page":"14515","article-title":"Spatial memory, recognition memory, and the hippocampus","volume":"101","author":"Broadbent","year":"2004"},{"key":"b5-jns091212","series-title":"Mol Cell Proteomics","first-page":"1158","article-title":"Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum","volume":"5","author":"Cheng","year":"2006"},{"key":"b6-jns091212","series-title":"Stroke","first-page":"1799","article-title":"Size matters: hemorrhage volume as an objective measure to define significant intracranial hemorrhage associated with thrombolysis","volume":"38","author":"Christoforidis","year":"2007"},{"key":"b7-jns091212","series-title":"J Biol Chem","first-page":"43329","article-title":"Astrocyte protection of neurons: role of transforming growth factor-beta signaling via a c-Jun-AP-1 protective pathway","volume":"278","author":"Dhandapani","year":"2003"},{"key":"b8-jns091212","series-title":"J Neurosci","first-page":"916","article-title":"Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity","volume":"24","author":"Ehrlich","year":"2004"},{"key":"b9-jns091212","series-title":"Neuron","first-page":"307","article-title":"Synapse-specific and developmentally regulated targeting of AMPA receptors by a family of MAGUK scaffolding proteins","volume":"52","author":"Elias","year":"2006"},{"key":"b10-jns091212","series-title":"Neuroscience","first-page":"1213","article-title":"Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade","volume":"94","author":"Fink","year":"1999"},{"key":"b11-jns091212","series-title":"J Comp Neurol","first-page":"572","article-title":"Improved immunohistochemical detection of postsynaptically located PSD-95\/SAP90 protein family by protease section pretreatment: a study in the adult mouse brain","volume":"426","author":"Fukaya","year":"2000"},{"key":"b12-jns091212","series-title":"J Neurotrauma","first-page":"405","article-title":"Mild experimental brain injury in the rat induces cognitive deficits associated with regional neuronal loss in the hippocampus","volume":"10","author":"Hicks","year":"1993"},{"key":"b13-jns091212","series-title":"Neurology","first-page":"187","article-title":"Longitudinal cognitive changes in traumatic brain injury: a 30-year follow-up study","volume":"66","author":"Himanen","year":"2006"},{"key":"b14-jns091212","series-title":"Neuroscience","first-page":"483","article-title":"Persistent working memory dysfunction following traumatic brain injury: evidence for a time-dependent mechanism","volume":"159","author":"Hoskison","year":"2009"},{"key":"b15-jns091212","series-title":"J Neurotrauma","first-page":"1545","article-title":"Inflammation in human brain injury: intracerebral concentrations of IL-1alpha, IL-1beta, and their endogenous inhibitor IL-1ra","volume":"24","author":"Hutchinson","year":"2007"},{"key":"b16-jns091212","series-title":"Prog Brain Res","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0079-6123(06)61016-9","article-title":"Cerebral contusion: a role model for lesion progression","volume":"161","author":"Kawamata","year":"2007"},{"key":"b17-jns091212","series-title":"Nat Rev Neurosci","first-page":"771","article-title":"PDZ domain proteins of synapses","volume":"5","author":"Kim","year":"2004"},{"key":"b18-jns091212","series-title":"Synapse","first-page":"1","article-title":"Widespread expression of olfactory cyclic nucleotide-gated channel genes in rat brain: implications for neuronal signalling","volume":"32","author":"Kingston","year":"1999"},{"key":"b19-jns091212","series-title":"J Neurotrauma","first-page":"247","article-title":"Selective vulnerability of hippocampal neurons in acceleration-induced experimental head injury","volume":"8","author":"Kotapka","year":"1991"},{"key":"b20-jns091212","series-title":"J Neurotrauma","first-page":"317","article-title":"Hippocampal pathology in fatal human head injury without high intracranial pressure","volume":"11","author":"Kotapka","year":"1994"},{"key":"b21-jns091212","series-title":"Acta Neuropathol","first-page":"530","article-title":"Hippocampal pathology in fatal non-missile human head injury","volume":"83","author":"Kotapka","year":"1992"},{"key":"b22-jns091212","series-title":"J Neurochem","article-title":"Curcumin attenuates cerebral edema following traumatic brain injury in mice: a possible role for aquaporin-4?","author":"Laird","year":"2010"},{"key":"b23-jns091212","series-title":"Proc Natl Acad Sci U S A","first-page":"19902","article-title":"PSD-95 and PKC converge in regulating NMDA receptor trafficking and gating","volume":"103","author":"Lin","year":"2006"},{"key":"b24-jns091212","series-title":"J Neurosci","first-page":"10138","article-title":"Postsynaptic density protein-95 regulates NMDA channel gating and surface expression","volume":"24","author":"Lin","year":"2004"},{"key":"b25-jns091212","series-title":"Brain Inj","first-page":"271","article-title":"Prospective and declarative memory problems following moderate and severe traumatic brain injury","volume":"19","author":"Mathias","year":"2005"},{"key":"b26-jns091212","series-title":"J Neuropathol Exp Neurol","first-page":"272","article-title":"There is differential loss of pyramidal cells from the human hippocampus with survival after blunt head injury","volume":"62","author":"Maxwell","year":"2003"},{"key":"b27-jns091212","series-title":"J Neurotrauma","first-page":"1023","article-title":"Prolonged activation of NF-kappaB following traumatic brain injury in rats","volume":"16","author":"Nonaka","year":"1999"},{"key":"b28-jns091212","series-title":"J Neurotrauma","first-page":"798","article-title":"Post-injury administration of mitochondrial uncouplers increases tissue sparing and improves behavioral outcome following traumatic brain injury in rodents","volume":"24","author":"Pandya","year":"2007"},{"key":"b29-jns091212","series-title":"Hippocampus","first-page":"390","article-title":"Glutamate antagonism during secondary deafferentation enhances cognition and axo-dendritic integrity after traumatic brain injury","volume":"8","author":"Phillips","year":"1998"},{"key":"b30-jns091212","series-title":"Nat Neurosci","first-page":"794","article-title":"Molecular determinants of NMDA receptor internalization","volume":"4","author":"Roche","year":"2001"},{"issue":"12 Suppl","key":"b31-jns091212","series-title":"Arch Phys Med Rehabil","first-page":"S69","article-title":"Long-term cognitive outcome in moderate to severe traumatic brain injury: a meta-analysis examining timed and untimed tests at 1 and 4.5 or more years after injury","volume":"89","author":"Ruttan","year":"2008"},{"key":"b32-jns091212","series-title":"Endocrine","first-page":"389","article-title":"Suberoylanilide hydroxamic acid (SAHA) induces growth arrest and apoptosis in pituitary adenoma cells","volume":"35","author":"Sangeetha","year":"2009"},{"key":"b33-jns091212","series-title":"J Neurosci","first-page":"1260","article-title":"A developmental change in NMDA receptor-associated proteins at hippocampal synapses","volume":"20","author":"Sans","year":"2000"},{"key":"b34-jns091212","series-title":"Science","first-page":"1845","article-title":"Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein","volume":"284","author":"Sattler","year":"1999"},{"key":"b35-jns091212","series-title":"Hippocampus","first-page":"541","article-title":"Mechanisms underlying the inability to induce area CA1 LTP in the mouse after traumatic brain injury","volume":"16","author":"Schwarzbach","year":"2006"},{"key":"b36-jns091212","series-title":"J Neurol Neurosurg Psychiatry","first-page":"129","article-title":"Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury","volume":"76","author":"Serra-Grabulosa","year":"2005"},{"key":"b37-jns091212","series-title":"Learn Mem","first-page":"442","article-title":"Fornix and hippocampal atrophy in traumatic brain injury","volume":"7","author":"Tate","year":"2000"},{"issue":"12 Suppl","key":"b38-jns091212","series-title":"Arch Phys Med Rehabil","first-page":"S25","article-title":"Postrecovery cognitive decline in adults with traumatic brain injury","volume":"89","author":"Till","year":"2008"},{"key":"b39-jns091212","series-title":"J Neurol Neurosurg Psychiatry","first-page":"1314","article-title":"Gross morphology and morphometric sequelae in the hippocampus, fornix, and corpus callosum of patients with severe non-missile traumatic brain injury without macroscopically detectable lesions: a T1 weighted MRI study","volume":"75","author":"Tomaiuolo","year":"2004"},{"key":"b40-jns091212","series-title":"Antioxid Redox Signal","first-page":"35","article-title":"Curcumin attenuates vascular inflammation and cerebral vasospasm after subarachnoid hemorrhage in mice","volume":"11","author":"Wakade","year":"2009"},{"key":"b41-jns091212","series-title":"Acta Neuropathol","first-page":"581","article-title":"In situ DNA fragmentation occurs in white matter up to 12 months after head injury in man","volume":"102","author":"Williams","year":"2001"}],"container-title":["Journal of Neurosurgery"],"original-title":[],"link":[{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/113\/6\/article-p1195.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/113\/6\/article-p1195.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/thejns.org\/downloadpdf\/journals\/j-neurosurg\/113\/6\/article-p1195.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T03:23:05Z","timestamp":1679887385000},"score":1,"resource":{"primary":{"URL":"https:\/\/thejns.org\/view\/journals\/j-neurosurg\/113\/6\/article-p1195.xml"}},"subtitle":["Laboratory investigation"],"short-title":[],"issued":{"date-parts":[[2010,12]]},"references-count":41,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.3171\/2010.3.jns091212","relation":{},"ISSN":["0022-3085","1933-0693"],"issn-type":[{"value":"0022-3085","type":"print"},{"value":"1933-0693","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,12]]}}}