A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke.

A genetic deficiency in folic acid metabolism impairs recovery after ischemic stroke. Exp Neurol. 2018 Jul 25;: Authors: Jadavji NM, Emmerson JT, Shanmugalingam U, MacFarlane AJ, Willmore WG, Smith PD Abstract Stroke is a leading cause of disability and death world-wide and nutrition is a modifiable risk factor for stroke. Metheylenetetrahydrofolate reductase (MTHFR) is an enzyme involved in the metabolism of folic acid, a B-vitamin. In humans, a polymorphism in MTHFR (677C→T) is linked to increased risk of stroke, but the mechanisms remain unknown. The Mthfr+/- mice mimic a phenotype described in humans at bp677. Using this mouse model, the aim of this study was to investigate the impact of MTHFR deficiency on stroke outcome. Male Mthfr+/- and wildtype littermate control mice were aged (~1.5-year-old) and trained on the single pellet reaching task. After which the sensorimotor cortex was then damaged using photothrombosis (PT), a model for ischemic stroke. Post-operatively, animals were tested for skilled motor function, and brain tissue was processed to assess cell death. Mthfr+/- mice were impaired in skilled reaching 2-weeks after stroke but showed some recovery at 5-weeks compared to wild types after PT damage. Within the ischemic brain, there was increased expression of active caspase-3 and reduced levels of phospho-AKT in neurons of Mthfr+/- mice. Recent data suggests that astrocytes may play a significant role after damage,...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research