Stroke is one of the most deliberating causes of mortality and disability worldwide. Studies have implicated Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene as a genetic factor influencing stroke recovery. Still, the role of BDNF polymorphism in poststroke aphasia is relatively unclear. This review assesses the recent evidence on the association between the BDNF polymorphism and aphasia recovery in poststroke patients. The article highlights BNDF polymorphism characteristics, speech and language interventions delivered, and the influence of BNDF polymorphism on poststroke aphasia recovery. We conducted a literature search through PubMed and Google Scholar with the following terms: "brain derived-neurotrophic factor" and "aphasia" for original articles from January 2000 until June 2020. Out of 69 search results, a detailed selection process produced a total of 3 articles that met the eligibility criteria. All three studies included Val66Met polymorphism as the studied human BDNF gene. One of the studies demonstrated insufficient evidence to conclude that BDNF polymorphism plays a role in poststroke aphasia recovery. The remaining two studies have shown that Met allele genotype (either single or double nucleotides) was associated with poor aphasia recovery, in either acute or chronic stroke. Carriers of the Val66Met polymorphism of BDNF gave a poorer response to aphasia intervention and presented with more severe aphasia.
The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood-brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.