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.