Abstract TP215: Prenatal Alcohol Exposure Impairs Long-term Behavioral Recovery Following Ischemic Stroke In Sprague Dawley Rats

Background and Purpose: Early life adversity is an important risk factor for cardiometabolic diseases in adulthood. There is very little information on prenatal insults and adult stroke outcomes. The present study tested the hypothesis that prenatal alcohol exposure (PAE) impedes long-term recovery from ischemic stroke in rats.

Methods: Pregnant Sprague Dawley rats (in-house bred) were exposed to 10% alcohol or air, for 1 hour from gestational day 8 through 18 using the rodent alcohol inhalation system. Adult offspring (5-6 mo old) were subjected to endothelin-1 induced MCAo and outcomes were evaluated after 180 days. Long-term cognitive outcomes were determined using the Barnes maze and fear conditioning/extinction test.

Results: In the Barnes maze test, control males showed shorter latency to reach the goal box over 3-day learning period (p=0.002), as assessed by the slope of the curve (-27.66, significantly different from 0; p=0.005). In contrast, the latency over the 3-day learning period did not improve in PAE males (-9.674, not significantly different from 0; p=0.22). In females, the latency to escape box during the learning trials was not different between the control and PAE. The fear conditioning data indicate that percent freezing over trials was similar in control and PAE-males. However, the PAE females exhibited a diminished freezing response as compared to control females (p=0.01). In the context of fear extinction, control males showed a reduction in freezing response to repeated tones over the trial blocks (p=0.004) compared to PAE-males. The control and PAE females showed similar freezing responses with repeated tones.

Conclusions: The present findings support the hypothesis that PAE modifies long-term cognitive changes after stroke, and further show that different cognitive domains are affected by PAE in males and females.