NEW YORK (Reuters Health) - Experiments in mice show that folate deficiency is associated with increased oxidative DNA damage and ischemic lesion size following middle cerebral artery (MCA) occlusion and reperfusion.
Dr. Matthias Endres, of Humboldt University, Berlin, Germany, and colleagues note in the February issue of Stroke that folate deficiency and the resulting hyperhomocysteinemia impair vascular function and increase the risk of stroke.
To investigate further, the team exposed several strains of mice to a folate-deficient diet or normal diet for 3 months. “After 3 months on the diets, serum levels of homocysteine were determined and were found to be 7-fold increased in animals subjected to the folate-deficient diet,” Dr. Endres’ team notes.
The animals then underwent 30-minute MCA occlusion followed by reperfusion.
Folate-deficient wild-type mice exhibited a significant 2.2-fold increase in cerebral lesion volume and neurological deficits after MCA occlusion and 72-hour reperfusion compared with mice on a normal diet.
Apurinic/apyrimidinic abasic sites (AP sites) -- signs of oxidative damage -- were significantly increased in DNA from the ischemic brain of folate-deficient mice early after MCA occlusion/reperfusion.
Brain lesion size was further increased in folate-deficient animals lacking uracil-DNA glycosylase compared with wild-type littermate mice. The researchers say this emphasizes the importance of uracil base excision repair in ischemic cell death.
“By inference, lowering homocysteine levels by vitamin therapy may provide a therapy not only to reduce stroke risk but to protect the brain from neurodegeneration during cerebral ischemia,” the investigators conclude.
Source: Stroke 2005;36:321-325. [ Google search on this article ]
MeSH Headings:Folic Acid Deficiency: Mice, Inbred Strains: Animals, Inbred Strains: HyperhomocysteinemiaCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
