Background and Purpose: Metabolic and cardiovascular disease in later life may have developmental origins. The present study specifically tested the hypothesis that fetal alcohol exposure (FAE) will persistently influence blood flow in adulthood and result in greater impairment following ischemic stroke.
Methods: Timed-pregnant C57Bl/6 female mice (GD12) were intragastrically gavaged with ethanol (3g/kg/bwt) or water twice per day from GD12 through 15. At 3 months of age, FAE and control males and females were subject to high-resolution ultrasound pulsed-wave Doppler imaging to record blood flow in carotid, abdominal, renal and femoral arteries. Blood flow was quantified. Thereafter, mice were subjected to middle cerebral artery occlusion (MCAo) using an intraluminal filament and sacrificed at 24 h post-stroke. Stroke induced brain damage was assessed by behavioral assays (adhesive tape test), neurological score and infarct volume.
Results: Blood flow measurements indicated that fetal alcohol exposure increased acceleration in renal lobar arteries of ethanol exposed females (P<0.003), indicating that alcohol exposure may lead to impairment vascular tone and early signs of hypertension in end organs like kidney. In animals subject to MCAo, FAE adults exhibited greater neurological deficits at 24h post-stroke, as determined by their higher scores on a combination of different parameters of motor impairment and behavioral measures (neurologic score) compared to controls (P<0.0004). Sensorimotor deficits assessed by sticky tape test also showed that fetal alcohol exposed animals were severely affected (p<0.05) indicating that developmental alcohol exposure can impair adaptation in adult brain to an acute neural damage. There is also a significant correlation between the neurological scores and infarct volume in FAE females (p<0.05) but not FAE males, suggesting sex differences in response to FAE modify the relationship between stroke and outcomes.
Conclusions: Our findings support a hypothesis that fetal alcohol exposure has long lasting and sexually dimorphic effects on adult health, resulting in impaired renal blood flow and poor stroke outcomes.