Cerebral blood flow dynamics have long been linked to neural activity, and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. But how such blood flow changes are mediated has remained controversial. Here, David Attwell and colleagues reveal how neuronal activity can hyperpolarize pericytes, leading to their relaxation and capillary dilation. Capillary dilation is responsible for 84% of the blood increase linked to neural activity, so irreversible capillary closure due to pericyte death during ischaemia can injure the blood–brain barrier and exacerbate injury. Pericyte death under pathological conditions can be reduced if glutamate receptor signalling is inhibited. This work suggests that pericytes are major regulators of cerebral blood flow and may initiate BOLD imaging signals.
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