ACUTE INCREASE IN EXPRESSION OF GROWTH-ASSOCIATED PROTEIN GAP-43 FOLLOWING CORTICAL ISCHEMIA IN RAT

Focal cerebral ischemia creates an area of infarction that is surround ed by neuronal tissue that may respond to nearby damage by creating ne urite growth. To determine if axonal sprouting occurs after infarction , antibodies to growth associated protein MW 43,000 (GAP-43), a protei n expressed on axonal growth cones, were used to assess the level of G AP-43 immunoreactivity as a measure of sprouting. Cerebral ischemia wa s induced in spontaneously hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid arter y. After 1 week of recovery, the animals were perfused, the brains rem oved, processed, and optical densities of the immunuoreaction were mea sured. The cortex surrounding the infarcted area had increased optical densities (xBAR +/- S.D. = 14.2% +/- 5.5) compared to the optical den sity values measured in similar areas in the contralateral hemisphere (xBAR +/- S.D. = 6.0% +/- 3.3), a 136% increase that is statistically significant, P < 0.05 Student's t-test. We hypothesize that this incre ase in GAP-43 reaction product is due to axonal sprouting in the corte x surrounding an area of infarction. These data, coupled with previous work examining-synaptophysin levels after cortical infarction, suppor t the hypothesis of sprouting and synaptogenesis in the cortex followi ng cerebral infarction.