The effect of postischemic blood glucose levels on ischemic brain damage in the rat.
The effect of insulin-induced hypoglycemia following 10.5 minutes of forebrain ischemia was studied in the rat. All groups received preischemic glucose loading (2 gm/kg) to promote brain infarction. Following completion of ischemia, rats received either 2 to 3 IU/kg (low-dose group) or 8 to 20 IU/kg (high-dose group) insulin. During the survival period, blood glucose concentrations were maintained in the ranges of 1.2 to 2.9 mM and 2.9 to 4.9 mM, respectively, for the low-dose and high-dose insulin groups. Control rats were given 2 gm/kg glucose immediately following ischemia. During the recovery period, until perfusion at 7 days, they were given glucose, 2 gm/kg, twice daily by intraperitoneal injection, and their drinking water was supplemented with 25% glucose. Mortality (p less than 0.05) and postischemic seizure incidence (p less than 0.01) were significantly reduced in the low-dose insulin group compared to the control group. Mortality was increased in the high-dose insulin group compared to the control group and was associated with an increased incidence of postischemic seizures. Neuropathological examination revealed no cortical infarction in the low-dose or high-dose insulin-treated rats compared to a 60% incidence of cortical infarction in the control group. In addition, the high-dose insulin-treated group showed a significant reduction in striatal and hippocampal CA1 selective neuronal necrosis compared to control rats with comparable survivals (p less than 0.05). The findings suggest that postischemic blood glucose concentrations play an important role in modulating both ischemic infarction and selective neuronal necrosis.
Voll
C L
CL
Department of Pathology, University of Calgary, Alberta, Canada.
Auer
R N
RN
D000818:Animals; D001786:Blood Glucose / Q000502:physiology*; D002545:Brain Ischemia / Q000097:blood* / Q000401:mortality / Q000473:pathology; D002544:Cerebral Infarction / Q000097:blood / Q000401:mortality / Q000473:pathology; D004334:Drug Administration Schedule; D005951:Glucose Tolerance Test; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin