Journal of Neurology and Neuroscience

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The Potential Therapeutic Value of BDNF-TrkB Pathway in COVID-19 Associated Stroke

Sanketh Andhavarapu, Joseph Bryant, Volodymr Gerzanich, Marc J Simard and Tapas Kumar Makar

Infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was declared the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) on March 11th, 2020. While most symptoms are those associated with the respiratory system, common symptoms also involve the nervous system. Stroke is a common complication of COVID-19, and it has been stated that future research should investigate the underlying mechanisms of COVID-19 associated thrombosis in order to develop preventative strategies for complications such as ischemic stroke. This is likely because SARS-CoV-2 binds to the angiotensin converting enzyme 2 (ACE2) receptor, and decreased activity of ACE2 promotes risk of stroke by causing an imbalance of the renin-angiotensin system. ACE2 is an enzyme that plays a role in the release of neurotrophic factors such as brain derived neurotrophic factor (BDNF), which plays a critical role in neurogenesis, cognitive function, and neurodevelopment. Earlier, it has been reported that the BDNF-TrkB system is neuroprotective during stroke. BDNF-TrkB signalling acts as a mediator of the renin-angiotensin system in the brain, and this regulatory effect may be disturbed during COVID-19 infection. This review consolidates the existing literature on the extensive role of the renin-angiotensin system and angiogenesis in COVID-19 and stroke with a focus on the BDNF-TrkB pathway. We hypothesize that the risk for stroke is higher in COVID-19 patients due to inhibition of BDNF that results from the downregulation of the ACE2 receptor during infection of SARS-CoV-2. In parallel, this review suggests that BDNF therapy may reduce the risk of stroke events and/or aid post-stroke recovery in COVID-19 patients.