Insulin administration protects neurologic function in cerebral ischemia in rats.
Hyperglycemia exacerbates neurologic damage in clinical and experimental central nervous system ischemia. The purpose of our study was to determine if insulin administration before significantly alters neurologic deficit and survival after ischemia using a newly developed rat cerebral ischemia model. One hour before the onset of ischemia, 40 200-300-g Sprague-Dawley rats received intraperitoneal injections of either 1 ml normal saline or 0.4, 0.5, or 0.6 units regular insulin in 1 ml normal saline. Rats were then intubated and ventilated with 1-1.5% halothane. The aortic arch was exposed, and snares were placed on the innominate, left carotid, and left subclavian arteries. A 20-minute occlusion was begun, and anesthesia was discontinued. Baseline plasma glucose concentration was similar (p = 0.48, Student's t test) in both groups, but it subsequently was significantly lower in the 0.4 unit insulin-treated group up to 4 hours after occlusion (p less than or equal to 0.0035, Student's t test). Neurologic deficit was scored on a 50-point scale (0 = normal, 50 = severe deficit) 1, 4, 18, and 24 hours after occlusion. In the 0.4 unit insulin-treated group the neurologic deficit score was significantly lower than in the saline-treated group 1, 4, 18, and 24 hours after occlusion (p less than or equal to 0.005, Student's t test). Survival was significantly higher (p = 0.001) in the 0.4 unit insulin-treated (1.7 unit/kg dose) group than in the saline-treated group. No rats died when preocclusion plasma glucose concentration was between 65 and 175 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)
LeMay
D R
DR
Department of Physiology and Surgery, University of Michigan Medical School, Ann Arbor 48109.
Gehua
L
L
Zelenock
G B
GB
D'Alecy
L G
LG
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002545:Brain Ischemia / Q000097:blood / Q000401:mortality / Q000503:physiopathology*; D004569:Electroencephalography; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008991:Monitoring, Physiologic; D009420:Nervous System / Q000503:physiopathology*; D009422:Nervous System Diseases / Q000209:etiology / Q000517:prevention & control; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin