Specific Aims

Cerebral blood flow impairments are implicated in the pathogenesis of myriad neurological diseases, from concussion to dementia. Understanding how cerebral blood flow is regulated under normal conditions may thus permit the development of therapies that can correct blood flow abnormalities and thereby alter the trajectory of neurological diseases. Studies consistently reveal two broad categories of blood flow impairment: 1. abnormal perfusion (hypo- or hyperperfusion), and 2. dampened vasodynamics, defined as a reduced ability of the cerebrovasculature to rapidly change resistance to blood flow in response to environmental shifts such as neural activity, blood pressure, oxygen level, etc. While it is accepted that arterioles ensheathed by vascular smooth muscle cells (VSMCs) are capable of regulating perfusion and vasodynamics, it is debated whether capillaries lined with pericytes can also regulate blood flow. The goal of this dissertation is to clarify the capacity for pericyte-lined capillaries to regulate cerebral blood flow under non-pathological conditions.

Pericytes are by definition juxtaposed to the vascular lumen, giving them perfect posturing positioning  for cerebral  blood flow regulation. However, numerous studies have shown that only some populations of pericytes are equipped with contractile proteins, particularly those near arterioles and venules. These immunohistochemical findings are supported by in vivo investigations which show that some