Folate Deficiency Increases Postischemic Brain Injury

Abstract

Background and Purpose— Folate deficiency and resultant hyperhomocysteinemia impair vascular function and increase stroke risk. We tested the hypothesis that folate deficiency and high homocysteine levels promote DNA damage and increase brain injury after cerebral ischemia/reperfusion. Methods— 129/Sv mice, uracil-DNA glycosylase–deficient (Ung−/−) mice, and Ung+/+ littermate mice were exposed to a folate-deficient diet for 3 months and then subjected to 30-minute middle cerebral artery (MCA) occlusion and reperfusion. Plasma homocysteine levels and physiological parameters were measured in selected animals. Outcome measures were neurological sensorimotor deficits, infarct size measured by computer-assisted volumetry, and oxidative DNA damage measured by a colorimetric assay. Results— Exposure to a folate-deficient diet for 3 months conferred ≈6- to 10-fold higher plasma homocysteine levels than those associated with a normal diet. Cerebral lesion volumes and neurological deficits after MCA occlusion and ...