Kainate postconditioning restores LTP in ischemic hippocampal CA1: Onset-dependent second pathophysiological stress

Postconditioning can be induced by a broad range of stimuli within minutes to days after an ischemic cerebral insult. A special form is elicited by pharmacological intervention called second pathophysiological stress. The present study aimed to evaluate the effects of low-dose (5 mg/kg) kainate postconditioning with onsets 0, 24 and 48 h after the ischemic insult on the hippocampal synaptic plasticity in a 2-vessel occlusion model in rat. The hippocampal function was tested by LTP measurements of Schaffer collateral-CA1 pyramidal cell synapses in acute slices and the changes in density of Golgi-Cox-stained apical dendritic spines. Postconditioning 0 and 24 h after ischemia was not protective, whereas 48-h-onset postconditioning resulted in the reappearance of a normal spine density (>100,000 spines) 3 days after ischemia, in parallel with the long-term restoration of the damaged LTP function. Similar, but somewhat less effects were observed after 10 days. Our data clearly demonstrate the onset dependence of postconditioning elicited by a subconvulsant dose of kainate treatment in global ischemia, with restoration of the structural plasticity and hippocampal function.

Postconditioning elicited by a subconvulsant dose of kainic acid (KA) treatment is onset-dependent in global ischemia, resulting in restoration of the structural plasticity and hippocampal function (LTP).Figure optionsDownload as PowerPoint slideHighlights
► Postconditioning (PC) can be induced by kainic acid in the post-ischemic hippocampus.
► LTP returns to the control level in the CA1 subfield.
► The structural basis is the restoration of the spines of the CA1 pyramidal cells.
► The optimal timepoint for PC is post-ischemic day 2, with an onset dependence.
► The beneficial effects of PC are long-lasting (≥8 days).