Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury and behavioral deficits. Pericytes influence blood-brain barrier (BBB) integrity and cerebral blood flow. Under hypoxic conditions, pericytes detach from perivascular locations increasing vessel permeability and neuronal injury. This study characterizes the time course of BBB dysfunction and pericyte coverage following murine experimental CCH secondary to bilateral carotid artery stenosis (BCAS). Mice underwent BCAS or sham operation. On post-procedure days 1, 3, 7 and 30, corpus callosum BBB permeability was characterized using Evans blue (EB) extravasation and IgG staining and pericyte coverage/count was calculated. The BCAS cohort demonstrated increased EB extravasation on postoperative days 1 ( p = 0.003) 3 ( p = 0.002), and 7 ( p = 0.001) when compared to sham mice. Further, EB extravasation was significantly greater ( p = 0.05) at day 3 than at day 30 in BCAS mice. BCAS mice demonstrated a nadir in pericyte coverage and count on post-operative day 3 ( p < 0.05, compared to day 7, day 30 and sham). Decreased pericyte coverage/count and increased BBB permeability are most pronounced on postoperative day 3 following murine CCH. This precedes any notable WM injury or behavioral deficits.

The purpose of this review is to describe recent clinical and epidemiological studies examining the adverse effects of urban air pollution on the central nervous system (CNS). Air pollution and particulate matter (PM) are associated with neuroinflammation and reactive oxygen species (ROS). These processes affect multiple CNS pathways. The conceptual framework of this review focuses on adverse effects of air pollution with respect to neurocognition, white matter disease, stroke, and carotid artery disease. Both children and older individuals exposed to air pollution exhibit signs of cognitive dysfunction. However, evidence on middle-aged cohorts is lacking. White matter injury secondary to air pollution exposure is a putative mechanism for neurocognitive decline. Air pollution is associated with exacerbations of neurodegenerative conditions such as Alzheimer’s and Parkinson’s Diseases. Increases in stroke incidences and mortalities are seen in the setting of air pollution exposure and CNS pathology is robust. Large populations living in highly polluted environments are at risk. This review aims to outline current knowledge of air pollution exposure effects on neurological health.

Epidemiological studies have established an association between air pollution particulate matter exposure (PM2.5) and neurocognitive decline. Experimental data suggest that microglia play an essential role in air pollution PM-induced neuroinflammation and oxidative stress. This study examined the effect of nano-sized particulate matter (nPM) on complement C5 deposition and microglial activation in the corpus callosum of mice (C57BL/6J males). nPM was collected in an urban Los Angeles region impacted by traffic emissions. Mice were exposed to 10 weeks of re-aerosolized nPM or filtered air for a cumulative 150 hours. nPM-exposed mice exhibited reactive microglia and 2-fold increased local deposition of complement C5/ C5α proteins and complement component C5a receptor 1 (CD88) in the corpus callosum. However, serum C5 levels did not differ between nPM and filtered air cohorts. These findings demonstrate white matter C5 deposition and microglial activation secondary to nPM exposure. The C5 upregulation appears to be localized to the brain.

Objectives Chronic cerebral hypoperfusion (CCH) can result in vascular dementia and small vessel white matter ischemic injury. These findings have previously been demonstrated in a murine experimental model of CCH secondary to bilateral common carotid artery stenosis (BCAS). This study sought to elucidate the effects of CCH on recognition memory as assessed by the novel object recognition (NOR) test and histological analysis of the hippocampus and perirhinal cortex. Methods Studies were performed on ten-week-old male mice using bilateral 0.18 mm microcoils to narrow the carotid arteries in accordance with prior publications. Following surgery, BCAS (n = 6) and sham (n = 6) mice were evaluated using NOR and 8-arm radial maze testing paradigms. Tissue damage was assessed using H&E staining on a parallel cohort of mice (n = 6 BCAS, n = 7 sham). Results In the NOR paradigm, BCAS mice demonstrated significant deficits in short-term memory. Consistent with prior studies, BCAS mice also performed significantly worse on 8-arm radial maze testing. BCAS mice exhibited significantly more neuronal injury in the perirhinal cortex when compared to sham-operated mice. However, no significant differences in neuronal damage were observed in the CA1 region of the hippocampus. Discussion Experimental CCH secondary to BCAS results in recognition memory deficits on NOR testing. Damage to the perirhinal cortex, rather than to the hippocampus, may underlie this impairment.

This study demonstrates a potentially protective role for oral estradiol therapy in the setting of white matter injury and declarative memory deficits secondary to murine chronic cerebral hypoperfusion.