Characterization of the microglial response to cerebral ischemia in the stroke-prone spontaneously hypertensive rat

Stroke-prone spontaneously hypertensive rats (SHRSP) sustain more ischemic damage after middle cerebral artery occlusion than do their reference strai n, the Wistar-Kyoto rat (WKY). The cause of increased stroke sensitivity is still under investigation. In general, SHRSP display a greater response to inflammatory stimuli than do WKY. Because inflammatory cells may influence the extent of damage in experimental stroke, this study has investigated t he acute inflammatory response to focal ischemia in SHRSP and WKY. Adult ma le SHRSP (n=5) and WKY (n=5) were anesthetized and underwent distal middle cerebral artery occlusion. After 24 hours of recovery, infarct volume, neut rophil counts, and activated microglia counts were performed. SHRSP display ed more ischemic damage than did WKY (135 +/-4.7 versus 102 +/-4.7 mm(3) [m ean +/- SEM], P <0.005). Brain neutrophil counts were extremely low in both strains. SHRSP displayed significantly more activated microglia than did W KY in the ipsilateral hemisphere (respective SHRSP versus WKY values [mean SEM] were 88 +/-3.6 versus 51 +/-3.4 per mm(2) for the cortical peri-infarc t region [P <0.005] and 183 +/-7.9 versus 156 +/-3.7 per mm(2) for the infa rct core [P <0.05]) and in the contralateral hemisphere (eg, respective SHR SP versus WKY values were 102 +/-3.2 versus 50 +/-3.1 per mm(2) for the sen sorimotor cortex [P <0.0001]). No neutrophils and very few activated microg lia were found within the brains of naive rats. However naive SHRSP possess ed more microglia (resting and activated) than did naive WKY. This study de monstrates a more pronounced microglial response to focal ischemia in SHRSP compared with WKY and provides evidence of a potential role for inflammato ry processes in response to ischemic damage.