PMID- 24022623 OWN - NLM STAT- MEDLINE DCOM- 20140203 LR - 20211021 IS - 1559-7016 (Electronic) IS - 0271-678X (Print) IS - 0271-678X (Linking) VI - 33 IP - 12 DP - 2013 Dec TI - Uncoupling PSD-95 interactions leads to rapid recovery of cortical function after focal stroke. PG - 1937-43 LID - 10.1038/jcbfm.2013.153 [doi] AB - Since the most significant ischemic sequelae occur within hours of stroke, it is necessary to understand how neuronal function changes during this time. While histologic and behavioral models show the extent of stroke-related damage, only in vivo recordings can illustrate changes in brain activity during stroke and validate effectiveness of neuroprotective compounds. Spontaneous and evoked field potentials (fEPs) were recorded in the deep layers of the cortex with a linear microelectrode array for 3 hours after focal stroke in anesthetized rats. Tat-NR2B9c peptide, which confers neuroprotection by uncoupling the PSD-95 protein from N-methyl-D-aspartate receptor (NMDAR), was administered 5 minutes before ischemia. Evoked field potentials were completely suppressed within 3 minutes of infarct in all ischemic groups. Evoked field potential recovery after stroke in rats treated with Tat-NR2B9c (83% of baseline) was greater compared with stroke-only (61% of baseline) or control peptide (Tat-NR2B-AA; 67% of baseline) groups (P<0.001). Electroencephalography (EEG) power was higher in Tat-NR2B9c-treated animals at both 20 minutes and 1 hour (50% and 73% of baseline, respectively) compared with stroke-only and Tat-NR2B-AA-treated rats (P<0.05). Tat-NR2B9c significantly reduces stroke-related cortical dysfunction as evidenced by greater recovery of fEPs and EEG power; illustrating the immediate effects of the compound on poststroke brain function. FAU - Srejic, Luka R AU - Srejic LR AD - Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada. FAU - Hutchison, William D AU - Hutchison WD FAU - Aarts, Michelle M AU - Aarts MM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130911 PL - United States TA - J Cereb Blood Flow Metab JT - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JID - 8112566 RN - 0 (Disks Large Homolog 4 Protein) RN - 0 (Dlg4 protein, rat) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Peptides) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - D45TI2TWMA (Tat-NR2B9c) SB - IM MH - Animals MH - Brain Ischemia/*drug therapy/*physiopathology MH - Cerebral Cortex/*drug effects/*physiopathology MH - Disks Large Homolog 4 Protein MH - Evoked Potentials/drug effects MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Male MH - Membrane Proteins/*metabolism MH - Neuroprotective Agents/*therapeutic use MH - Peptides/*therapeutic use MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/metabolism PMC - PMC3851903 EDAT- 2013/09/12 06:00 MHDA- 2014/02/04 06:00 PMCR- 2014/12/01 CRDT- 2013/09/12 06:00 PHST- 2013/04/10 00:00 [received] PHST- 2013/07/23 00:00 [revised] PHST- 2013/07/24 00:00 [accepted] PHST- 2013/09/12 06:00 [entrez] PHST- 2013/09/12 06:00 [pubmed] PHST- 2014/02/04 06:00 [medline] PHST- 2014/12/01 00:00 [pmc-release] AID - jcbfm2013153 [pii] AID - 10.1038/jcbfm.2013.153 [doi] PST - ppublish SO - J Cereb Blood Flow Metab. 2013 Dec;33(12):1937-43. doi: 10.1038/jcbfm.2013.153. Epub 2013 Sep 11.