{Reference Type}: Journal Article
{Title}: Metformin attenuates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion.
{Author}: He Y;Li Z;Shi X;Ding J;Wang X;
{Journal}: J Cereb Blood Flow Metab
{Volume}: 43
{Issue}: 2
{Year}: 2023 11 12
{Factor}: 6.96
{DOI}: 10.1177/0271678X231175189
{Abstract}: Vascular cognitive impairment and dementia (VCID) is a series of cognitive dysfunction associated with cerebrovascular diseases and currently lacks effective treatments. The white matter, which is essential for neuronal information processing and integration, is nourished by a network of capillaries and is vulnerable to chronic hypoperfusion. Here, we show that metformin, a widely used drug for the treatment of type 2 diabetes, alleviates the white matter damage and improves cognitive impairment in a mouse model of VCID established by bilateral carotid artery stenosis (BCAS)-induced chronic hypoperfusion. Mechanistically, metformin restores the dysfunctions of oligodendrocyte precursor cells (OPCs) under hypoxia. Metformin up-regulates prolyl hydroxylases 2 via activating the AMP-activated protein kinase pathway, leading to hypoxia-inducible factor-1α (HIF-1α) degradation in OPCs. These findings suggest that metformin may have a promising therapeutic role in alleviating cognitive abnormalities by ameliorating white matter damage of VCID.