Bdnf val66met polymorphism is Associated with Enhanced Motor Recovery Following Stroke

Background and Purpose: Genetics is one of several key factors that influence stroke recovery. A single nucleotide polymorphism (SNP) of the bdnf gene (Val66Met) is common in humans, ranging from 20-30% in Caucasians up to 70% in the Asian population. Previous studies show several disadvantages to carrying this allele in humans. However, the high rate of SNP occurrence raises the intriguing possibility of a selective advantage to carrying the Met allele, such as motor function. The current study investigates the impact of bdnf val66met SNP on long term recovery after stroke. Methods: Mice with a genetic knock-in of the human BDNF variant (val66met) were generated. Adult male BDNF +/+ (WT) and BDNF Met/Met (M/M) mice were subjected to the proximal middle cerebral artery occlusion. Motor and gait functions were assessed by rotarod and Catwalk analysis at acute phase and recovery phase. Anatomical volume analysis was evaluated by cresyl violet and Golgi staining at 6 months after stroke. Results: As previously reported (Qin et al., 2011), there was greater acute impairment in motor behavioral outcomes in M/M mice after stroke, compared to WT mice. However, M/M mice displayed significantly enhanced rotarod performance at 2 weeks and the enhancement was sustained up to 6 months post-stroke. Similarly, Catwalk gait analyses in swing speed and stride length showed that M/M mice exhibited enhanced gaits (i.e. faster and longer stride) than WT mice during long-term recovery phases, especially in the ipsilesional right hind limb. Since ipsilesional limbs are controlled by the contralesional hemisphere, sub-regional volumes in this hemisphere were assessed. M/M mice showed specifically increased striatal volume at 6 months post-ischemia. The increased striatal volume was also associated with higher dendritic complexity of medium spiny neurons in this region, which indicated that the contralesional anatomical plasticity may account for enhanced motor recovery in MM mice. Conclusions: The findings suggest that BDNF SNP may have selective advantage in enhancing motor/gait function through the contralesional hemisphere during stroke recovery. The study has clinical importance by providing a means to predict the course of stroke recovery based on an individual’s SNP.