Photothrombotic middle cerebral artery occlusion in spontaneously hypertensive rats: Influence of substrain, gender, and distal middle cerebral artery patterns on infarct size

Abstract

Background and Purpose - To analyze the effects of substrain and gender differences in spontaneously hypertensive rats (SHR) and distal middle cerebral artery (MCA) branching patterns on infarct size, we compared infarct volumes produced by photothrombotic distal MCA occlusion using SHR/Kyushu and SHR/Izumo (Izm). Methods - Twenty-four male and 8 female SHR/Kyushu, 15 male and 5 female SHR/Izm, and 6 male Wistar-Kyoto rats (WKY)/Izm (5 to 7 months old) were subjected to photothrombotic distal MCA occlusion, and infarct volumes were determined. Results - Although blood pressure levels were essentially the same between the two substrains of hypertensive rats, infarct volumes were significantly larger in the SHR/Kyushu substrain than in SHR/Izm of either sex (P < 0.001); infarct volumes in male and female SHR/Kyushu were 83.8±11.7 and 58.5±9.2 mm3, and those in male and female SHR/Izm were 61.5±0.7 and 34.8±7.9 mm3, respectively (values are mean±SD). Male SHR/Kyushu that had simple Y-shaped MCA showed smaller infarcts (75.8±14.6 mm3, n=11) than those with more branching (regular) MCA (93.2±19.1, n=13), the difference being significant (P=0.022). Male SHR/Izm with simple distal MCA also produced smaller infarctions than those with regular MCA (51.0±3.7 versus 68.9±8.7 mm3, P=0.0004). Conclusions - Photothrombotic occlusion of distal MCA in hypertensive rats provides a simple and reproducible model of focal ischemia. Most importantly, this study emphasizes the substantial variabilities in infarct sizes caused by the differences in substrains of SHR, gender, and distal MCA patterns.