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 strain, 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 the acute inflammatory response to focal ischemia in SHRSP and WKY. Adult male SHRSP (n=5) and WKY (n=5) were anesthetized and underwent distal middle cerebral artery occlusion. After 24 hours of recovery, infarct volume, neutrophil counts, and activated microglia counts were performed. SHRSP displayed more ischemic damage than did WKY (135+/-4.7 versus 102+/-4.7 mm(3) [mean+/-SEM], P<0.005). Brain neutrophil counts were extremely low in both strains. SHRSP displayed significantly more activated microglia than did WKY 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-infarct region [P<0.005] and 183+/-7.9 versus 156+/-3.7 per mm(2) for the infarct core [P<0.05]) and in the contralateral hemisphere (eg, respective SHRSP versus WKY values were 102+/-3.2 versus 50+/-3.1 per mm(2) for the sensorimotor cortex [P<0.0001]). No neutrophils and very few activated microglia were found within the brains of naive rats. However naive SHRSP possessed more microglia (resting and activated) than did naive WKY. This study demonstrates a more pronounced microglial response to focal ischemia in SHRSP compared with WKY and provides evidence of a potential role for inflammatory processes in response to ischemic damage.
Marks
L
L
Wellcome Surgical Institute, Southern General Hospital, University of Glasgow, Glasgow, Scotland.
Carswell
H V
HV
Peters
E E
EE
Graham
D I
DI
Patterson
J
J
Dominiczak
A F
AF
Macrae
I M
IM
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D020521:Stroke / Q000209:etiology