NEOCORTICAL NEURAL SPROUTING, SYNAPTOGENESIS, AND BEHAVIORAL RECOVERYAFTER NEOCORTICAL INFARCTION IN RATS

Background and Purpose Neuroanatomical plasticity is well described in lesions of the hippocampus but remains a subject of some controversy in the neocortex. The purpose of the present study was to measure the neocortical distribution and density of expression of proteins known t o be involved in neurite growth or synaptogenesis and to correlate the neocortical expression with behavioral recovery after a focal neocort ical infarction. Focal neocortical infarction creates a circumscribed lesion in the neocortex that provides a denervation stimulus for neuri te growth and synaptogenesis. Methods Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n = 4 per time point) by permanent occlusion of the distal middle cerebral arter y and ipsilateral common carotid artery. To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, GAP-43, a growth-associated protein ex pressed on axonal growth cones, and sy naptophysin, a calcium-binding protein found on synaptic vesicles, wer e examined by immunohistochemical techniques. The reaction product was measured, and the distribution was recorded. Since the resulting infa rction included a portion of the forelimb neocortex, behavioral assess ments of forelimb function that used the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochem ical studies. Recovery times were 3, 7, 14, 30, and 60 days after surg ery. Results Both GAP-43 and synaptophysin proteins demonstrated stati stically significant increases in the density of immunoreaction produc t as determined by optical density measurements in the neocortex of in farcted rats compared with sham controls. The GAP-43 was elevated to s tatistically significant levels in forelimb, hindlimb, and parietal ne ocortical regions medial and lateral to the infarction only at days 3, 7, and 14. In contrast, synaptophysin demonstrated no statistically s ignificant changes in expression at 3 or 7 days but demonstrated stati stically significant increases at 14, 30; and 60 days in the forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction as well as in the contralateral parietal neocortex. Behavio ral assessment of forelimb function indicated impairment of forelimb p lacement on the side contralateral to the infarction that trended towa rd control values at 14 days and was not significantly different from controls by 30 days. Conclusions These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex, ipsilatera l and contralateral to neocortical ischemia, in a pattern that corresp onds both spatially and temporally with behavioral recovery. Thus, neu roanatomical remodeling in the neocortex provides a mechanism for reco very of function.