Experimental stroke in the female diabetic, db/db, mouse

Diabetic hyperglycemia increases brain damage after cerebral ischemia in an imals and humans, although the underlying mechanisms remain unclear. Gender -linked differences in ischemic tolerance have been described but have not been studied in the context of diabetes. In the current study, we used a mo del of unilateral common carotid artery ligation, combined with systemic hy poxia, to study the effects of diabetes and gender on hypoxic-ischemic (HI) brain damage in the genetic model of Type II diabetes, the db/db, mouse. M ale and female, control and db/db, mice were subjected to right common caro tid artery ligation followed by varying periods of hypoxia (8% oxpgen/92% n itrogen) to assess mortality, infarct volume, and tissue damage by light mi croscopic techniques. End-ischemic regional cerebral blood flow (CBF) was d etermined using [C-14] iodoantipyrine autoradiography. Glycolytic and high energy phosphate compounds were measured in blood and brain by enzymatic an d fluorometric techniques. Gender and diabetes had significant effects on m ortality from HI and extent of brain damage in the survivors. Female mice w ere more resistant than their male counterparts, such that the severity (mo rtality and infarction size) in the male diabetics > female diabetics simil ar to male controls > female controls. Endischemic CBF and depletion of cer ebral high energy reserves were comparable among all groups. Surprisingly, female diabetic mice were more hyperglycemic and demonstrated a greater pro longed lactacidosis than the males; however, they were more resistant to da mage. The results suggest a unique pathophysiology of hypoxia-ischemia in t he female diabetic brain.