Acute effects of systemic inflammation upon the neuro-glial-vascular unit and cerebrovascular function.

Abstract

Background Brain health relies on a tightly regulated system known as neurovascular function whereby the cellular constituents of the neuro-glial-vascular unit (NGVU) regulate cerebral haemodynamics in accordance with neuronal metabolic demand. Disruption of neurovascular function impairs brain health and is associated with the development of disease, including Alzheimer’s disease. The NGVU is also a key site of action for neuroinflammatory responses and contributes to the transition of systemic inflammation to neuroinflammatory processes. Thus, systemic inflammatory challenges may cause a shift in NGVU operation towards neuroimmune over neurovascular actions, leading to altered neurovascular function. Methods To investigate this, rats were injected with lipopolysaccharide (LPS) (2mg/kg) to induce a systemic inflammatory response, or vehicle, and brain haemodynamic responses to sensory and non-sensory (hypercapnia) stimuli were assessed in vivo using optical imaging techniques. Following imaging, animals were perfused and their brains extracted to histologically characterise components of the NGVU to determine the association between altered underlying pathology and in vivo blood flow regulation. Results LPS-treated animals showed altered haemodynamic function and cerebrovascular dynamics six hours after LPS administration. Histological assessment identified a significant increase in astrogliosis, microgliosis and endothelial activation in LPS-treated animals. Conclusions Our data shows that an acutely induced systemic inflammatory response is able to rapidly alter in-vivo haemodynamic function and is associated with significant changes in the cellular constituents of the NGVU. We suggest that these effects are initially mediated by endothelial cells, which are directly exposed to the circulating inflammatory stimulus and have been implicated in regulating functional hyperaemia.

Disturbed microcirculation and hyperaemic response in a murine model of systemic inflammation

“…While some found that resting CBF increased and functional haemodynamic responses decreased as a result of LPS, 37,45,46 others found no changes to the resting CBF and an increased haemodynamic response as a result of LPS. 47 It should be noted that these studies were carried out in animals anesthetised with different compounds, confounding comparisons between them, and with the present study. Future studies using fully quantitative methods in awake animals along with quantitative measures of vascular dilation must be designed to address this proposal.…”