Acute effects of systemic inflammation upon neurovascular unit and cerebrovascular function.

Abstract

Background: Brain health relies on a tightly regulated system known as neurovascular function whereby the cellular constituents of the neurovascular unit (NVU) 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 (AD). The NVU is the site of action of neuroinflammatory responses and contributes to the transition of systemic inflammation to neuroinflammatory processes. Thus, systemic inflammatory challenges may cause a shift in the NVU focus, prioritising neuroimmune over neurovascular actions leading to altered neurovascular function. Methods: Rats were injected with lipopolysaccharide (LPS) (2mg/kg) or vehicle and haemodynamic responses to sensory and non-sensory (hypercapnia) stimuli were assessed in vivo. Following imaging, animals were perfused and their brain extracted to histologically characterise components of the NVU to determine the association between underlying pathology to altered blood flow regulation in vivo. Results: LPS-treated animals showed altered haemodynamic function and cerebrovascular dynamics 6 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 NVU. 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.