Abstract WMP109: Prenatal Alcohol Exposure Worsens Stroke Outcomes In Young Rats And Exacerbates Brain Damage In Ischemic Middle-aged Rats

Abstract

Background and Purpose: Endocrine imbalances and cardiovascular diseases in post-natal life have been linked to adverse prenatal environment. There is very little information on the developmental origin of adult diseases, particularly prenatal alcohol exposure and stroke outcomes. Recent studies indicate that adults with prenatal adult exposure (PAE) are at agreater risk for obesity, hypertension and hyperglycemia, all of which increase the risk for severe stroke. The present study tested the hypothesis that prenatal alcohol exposure (PAE) elevates stroke severity in young and middle-aged rats. Methods: Pregnant Sprague Dawley rats (bred in-house) were exposed to 10% alcohol or air, for 1 hour from gestational day 8 through18 using the rodent alcohol inhalation system. Plasma IGF-1 levels were determined using an ELISA kit. Adult offspring (5 and 12 mo old) were subjected to endothelin-1 induced MCAo and outcomes were evaluated after 2 days. Acute stroke-induced disabilities were assessed by neurological scores and vibrissae evoked fore-limb placement task as well as the extent of infarction. Results: While plasma IGF-1 levels were higher in young control males than females, levels were significantly reduced in young-PAE males (p<0.04) compared to control males. MCAo significantly increased mortality in young PAE-males compared to control-males or PAE and control females. Behavioral analysis indicates that young-PAE animals exhibited greater neurological deficits as determined by their higher composite neurological score compared to controls (p<0.03), although their infarct volume was not significantly different from control animals. However, MCAo in the middle-aged PAE rats caused significant behavioral deficits: higher neurological scores (p<0.03), greater cross midline impairment (p<0.03), and increased brain infarction (p<0.04) compared to control stroke rats. Conclusions: The present findings support the hypothesis that PAE contributes to adverse effects on stroke outcome as indicated by greater mortality and poor neurological function in young rats, which is exacerbated by age during the acute phase.(Funding support, NIAAA, AA026756)