Spreading depressions and periinfarct spreading depolarizations in the context of cortical plasticity

Abstract

Studies of cortical function-recovery require a comparison between normal and post-stroke conditions that lead to cortical metaplasticity changes. Focal cortical stroke impairs experience-dependent plasticity (ExDP) in the neighboring somatosensory cortex. A stroke usually evokes periinfarct depolarizations (PiDs)a spreading depression-like waves. Experimentally induced spreading depressions (SDs) affect gene expression and some of these changes persist for at least 30 days. Such changes are not only stroke-specific: migraine patients had prolonged protein changes after a single SD episode during migraine aura. This study investigates whether non-stroke depolarizations like SDs impair cortical ExDP similarly to the stroke. Rats were subjected to unilateral SDs. ExDP was induced by a month of contralateral partial whiskers deprivation. Cortical activity was mapped by [ 14 C]-2-deoxy-D-glucose (2DG) incorporation during stimulation of spared and contralateral homotopic whiskers. Whiskers deprivation after SDs resulted in normal cortical representation enlargement suggesting that SDs and PiDs depolarization have no influence on ExDP cortical map reorganization. The differences hypothetically influencing metaplasticity in rats were verified and compared between the SDs induced by high osmolarity KCl solution and the PiDs following cortical photothrombotic stroke (PtS).We conclude neither PiDs nor the previously proposed MMP-9, -3, -2 or COX-2 are directly responsible for cortical post-stroke metaplasticity changes. Only the interhemispheric activity equilibrium was more imbalanced after stroke. Hence, the interhemispheric interactions modified by stroke may be a promising target for future studies of post-stroke ExDP and convalescence. The results support also more global SDs-mediated modifications, that may have some implications for the migraine states interpretation.Keywords: 2-DG, barrel field, COX-2, MMP-2, MMP-3, MMP-9, periinfarct depolarizations, PiDs, photothrombotic stroke, SD, spreading depression, whiskers deprivation, cortical plasticity.PiDs. Slight increase of MMP-9 in thalamus was observed in all the operated animals.We compared also spreading waves of PiDs and SDs amplitude and duration and frequencies of spontaneous oscillations during the depression period. The PiDs amplitude of the depolarization was a bit lower than SDs but no other differences were observed. The interhemispheric activity ratio was the only difference more pronounced after stroke. Hence, the interhemispheric interactions modified by stroke may therefore be a promising target for future studies of post-stroke experience-dependent plasticity and convalescence.