vascular endothelial morphology and function [135–138], which may alter cerebral perfusion. Additionally, nicotine administered through means other than cigarette smoke may alter or impair vasomotor reactivity of cerebral arterioles through upregulation of Ca2+ channels and/or modulation of nitric oxide [136]. These processes may impact the functional integrity (e.g., vasomotor reactivity/responsivity) of the cerebrovasculature and may, at least partially, contribute to the decreased regional cerebral blood flow [114,115,139] and/or white matter disease [85,87–89,140,141] observed in chronic smoking. Both the neocortex and underlying WM are vulnerable to the effects of diffuse ischemia (see [142] and references therein). Correspondingly, it has been suggested that late-myelinating areas such as the frontal and temporal lobes may be particularly vulnerable to increased oxidative stress and cerebral hypoperfusion [143,144], both of which have been described in chronic smokers.
