Background: Neurovascular coupling, or functional hyperaemia, serves to match local cerebral blood flow (CBF) to regional neuronal energy use ensuring normal functioning of the brain1. This is thought to be accomplished by astrocytes that form a physical bridge between neurons and blood vessels2. However, in response to disease, astrocytes become activated and this may have significant consequences for cerebrovascular function. The aim of this study was to determine the effects of astrocyte activation on brain vasculature using in vivo magnetic resonance imaging (MRI), laser speckle contrast imaging (LSCI) and histology. Methods: Male rats (N=16) were anesthetized with 2% isoflurane and injected intracortically with either (i) a lentivirus expressing ciliary neurotrophic factor (Lv-CNTF; N=7) known to switch astrocytic phenotype to an activated state, or (ii) a self-inactivated lentivirus expressing LacZ (Lv-LacZ; N=9). 6 weeks later, animals were anaesthetised with 2% isoflurane, tracheotomised and artificially ventilated. The left femoral artery was cannulated for monitoring mean arterial blood pressure (MABP), blood gases (PaCO2 and PaO2) and pH. Animals underwent MRI to measure basal CBF and LSCI to measure the CBF response, to both electrical stimulation of the whisker pad and hypercapnic (CO2) challenge, under 1.2% isoflurane in 70%N2/30%O2, and maintained at ~ 37°C. Animals were transcardially perfusion-fixed under terminal anaesthesia and histology was performed post-mortem to detect molecular and cellular markers associated with astrocyte activation. All data are given as mean ± SEM and compared by paired t-test. Results: CBF responses to whisker-pad (9.7±2.0 vs 19.6± 3.3%; injected vs non-injected; p<0.05) and hypercapnic (44.7±7.3 vs 68.1±1.0%; injected vs non-injected; p<0.01) challenges were significantly reduced in the CNTF-Lv animals. Similarly basal CBF was significantly reduced (49.0±10.5 vs 59.9±10.0ml/100g/min; injected vs non-injected; p<0.05) and correlated closely with the area of astrocyte activation (p<0.05; r2=0.3). Histologically, astrocyte activation was associated with changes in the microvascular network. The use of hypoxic probe pimonidazole revealed hypoxia during astrocyte activation, and thus potential metabolic changes. No changes were observed in the LacZ-Lv animals. Conclusion and future directions: These findings suggest that metabolic and vascular changes associated with astrocyte activation may suppress neurovascular coupling, and thus alters normal functioning of the brain. In Nottingham, we aim to use cutting-edge imaging methods (e.g. Dynamic Nuclear Polarisation 13C magnetic resonance spectroscopy) to detect specific metabolic changes associated with astrocyte activation and chronic perfusion stress in ageing that could be modulated by nutrition and exercise.