Investigating cerebral blood flow regulation in response to nitric oxide, β adrenergic signaling and the loss of Foxf2 expression

Abstract

Background- There are conflicting reports in the literature regarding the mural cell, pericytes and/or vascular smooth muscle cells (VSMCs), responsible for regulating cerebral blood flow. Accordingly, this project aimed to addresses these conflicting reports by identifying the mural cell responsible for cerebral blood flow regulation, in vivo.  

Methods- The optical clarity of the zebrafish model was used to explore the ability of the mural cell-covered cerebral vasculature to relax and dilate in response to chemical signals. Mural cell activity was investigated at 4 days post-fertilization (dpf) and at 7dpf.

Results- Overall, pericyte-covered vessels were found to be less than 10µm in diameter while VSMC-covered vessels were larger than 10µm in diameter. In the presence of a vasodilating agent, pericyte-covered vessels only dilated at 4dpf, whereas VSMC-covered vessels dilated at both 4dpf and at 7dpf. Furthermore, a deficiency in forkhead box F2 (Foxf2) did not alter the range of cerebral vessel sizes covered by VSMCs as well as their ability to dilate to the same extent as those seen in wild type zebrafish.

Conclusions- The dilation of VSMC-covered vessels in response to a vasodilating agent suggests for their role in cerebral blood flow regulation. However, further investigations are needed to characterize the contractile activity of vascular mural cells when it comes to cerebral blood flow regulation in zebrafish.

* Indicates faculty mentor