Spreading Depressions and Periinfarct Spreading Depolarizations in the Context of Cortical Plasticity.

Studies of cortical function-recovery require a comparison between normal and post-stroke conditions that lead to changes in cortical metaplasticity. Focal cortical stroke impairs experience-dependent plasticity in the neighboring somatosensory cortex and usually evokes periinfarct depolarizations (PiDs) - spreading depression-like waves. Experimentally induced spreading depressions (SDs) affect gene expression and some of these changes persist for at least 30 days. In this study we compare the effects of non-stroke depolarizations that impair cortical experience-dependent plasticity to the effects of stroke, by inducing experience-dependent plasticity in rats with SDs or PiDs by a month of contralateral partial whiskers deprivation. We found that whiskers' deprivation after SDs resulted in normal cortical representation enlargement suggesting that SDs and PiDs depolarization have no influence on experience-dependent plasticity cortical map reorganization. PiDs and the MMP-9, -3, -2 or COX-2 proteins, which are assumed to influence metaplasticity in rats after stroke were compared between SDs induced by high osmolarity KCl solution and the PiDs that followed cortical photothrombotic stroke (PtS). We found that none of these factors directly caused cortical post-stroke metaplasticity changes. The only significant difference between stoke and induced SD was a greater imbalance in interhemispheric activity equilibrium after stroke. The interhemispheric interactions that were modified by stroke may therefore be promising targets for future studies of post-stroke experience-dependent plasticity and of recuperation studies.

Experience-dependent brain plasticity after stroke: effect of ibuprofen and poststroke delay.

Despite indications that brain plasticity may be enhanced after stroke, we have described impairment of experience-dependent plasticity in rat cerebral cortex neighboring the stroke-induced lesion. Photothrombotic stroke was centered behind the barrel cortex in one cerebral hemisphere of rats. Plasticity of cortical representation of one row of vibrissae was induced by sensory deprivation of all surrounding whiskers for 1 month, and visualized with [(14)C]-2-deoxyglucose autoradiography. In control rats deprivation resulted in an enlargement of functional cortical representation of the spared row of vibrissae. After a focal stroke neighbouring the barrel cortex, no plasticity of the spared row representation was found. Investigation of plastic changes with deprivation initiated 1 week and 1 month after stroke have shown that later poststroke onset of deprivation resulted in a partial recovery of cortical plasticity in the barrel field. Western blot analysis of proinflammatory enzyme cyclooxygenase-2 (COX-2) expression revealed its strong upregulation in the barrel cortex 24 h after stroke. When chronic treatment with the anti-inflammatory drug ibuprofen (10 mg/kg or 20 mg/kg) accompanied deprivation, plasticity was restored. Ibuprofen applied before the ischemia also prevented the poststroke upregulation of COX-2. The results strongly suggest that poststroke impairment of experience-dependent cortical plasticity is caused by stroke-induced inflammatory reactions that subside with poststroke delay and can be at least partially ameliorated by pharmacological treatment.

Photothrombotic infarct impairs experience-dependent plasticity in neighboring cortex.

Spontaneous restorative plasticity is reported frequently after stroke. To test whether conditions in perinfarct cortex facilitate plastic changes, we examined experience-dependent plasticity of cortical functional representation of vibrissae in rat brain after focal photothrombotic stroke. Cortical activation was visualized with [C]2-deoxyglucose. To induce plasticity, four rows of whiskers were trimmed on one side of the snout for a month, whereas one row was spared. This deprivation was started immediately after the stroke. In control rats, cortical representation of the spared row whiskers was significantly enlarged compared with undeprived controls. In rats with infarct posterior to the barrel cortex, no plastic change of the spared row representation was observed. We conclude that early after stroke, use-dependent plasticity is impaired in the perinfarct cortex.