Decreased expression of brain‐derived neurotrophic factor in BDNF^+/− mice is associated with enhanced recovery of motor performance and increased neuroblast number following experimental stroke

Abstract

Brain-derived neurotrophic factor (BDNF) is involved in brain plasticity and neuronal survival. Generally, BDNF enhances synaptic activity and neurite growth, although the effect of BDNF on neuronal survival and brain plasticity following injury is equivocal. Housing rats in an enriched environment after experimental stroke enhances recovery of sensory-motor function, which is associated with a decrease in the BDNF mRNA and protein levels. We used BDNF(+/-) mice and wild-type littermate mice to investigate whether the decrease in the brain levels of BDNF affected motor function or infarct volume following transient occlusion of the middle cerebral artery (tMCAO) for 40 min. We found that the BDNF(+/-) mice had a significantly improved motor function on the rotating pole test 2 weeks after tMCAO compared with wild-type mice. When intermittently exposed to an enriched environment following tMCAO, the wild-type mice improved motor function to the same degree as BDNF(+/-) mice. There was no effect of BDNF reduction on infarct volume. Neurogenesis is induced following experimental stroke, and in the striatum of BDNF(+/-) mice significantly increased numbers of neuroblasts compared with wild-type mice were seen, both in standard and in enriched conditions. We conclude that decreasing brain levels of BDNF enhances the recovery of function following experimental stroke.

BDNF −270 C>T polymorphisms might be associated with stroke type and BDNF −196 G>A corresponds to early neurological deficit in hemorrhagic stroke

“…It was also shown that BDNF might increase angiogenesis and behavioral recovery in mouse intracranial hemorrhage model (Lee et al, 2010), the same as in mouse ischemic stroke model (Qin et al, 2011). In our study BDNF −196 G>A polymorphism was not found to have any impact on human ischemic stroke within short-term observation, but some animal studies also argue against beneficial effect of BDNF in the model of cerebral ischemia (Gustafsson et al, 2003;Nygren et al, 2006).…”

Brain-Derived Neurotrophic Factor Contributes to Recovery of Skilled Reaching After Focal Ischemia in Rats

“…17 Alternatively, inhibiting BDNF appears to have the potential to attenuate recovery processes. 18 Recent findings show that healthy individuals with a val66met polymorphism in the BDNF gene show reduced ability to change cortical maps in response to motor training. 19 In addition, blocking BDNF decreases cAMP response-element-binding protein and synapsin 1, which are regulated by BDNF, and this impairs learning and memory.…”

Brain-Derived Neurotrophic Factor Knockdown Blocks the Angiogenic and Protective Effects of Angiotensin Modulation After Experimental Stroke

“…[18,19,29,52,53] Paradoxically, one study conducted in BDNF(+/−) mice showed enhanced functional recovery after stroke with decreased brain levels of BDNF. [54] Ploughman et al assessed the role of endogenous BDNF in rehabilitation induced stroke recovery through knocking down BDNF expression using antisense BDNF oligonucleotide infusion. Their data demonstrated an indispensable role of BDNF in rehabilitation induced recovery after stroke.…”