Age-related impairment of metabovascular coupling during cortical spreading depolarizations.

30 Cortical spreading depolarizations (SDs) may lead to long-lasting alterations in 31 cerebral blood flow (CBF), which contribute to neuronal dysfunction and hypoxic tissue 32 injury. There is growing evidence to suggest that age-related structural and functional 33 alterations of the neurovascular unit significantly increase both the incidence of SDs and 34 aggravate their functional consequences. Recent studies suggest that metabolic signaling plays 35 a major role in modulating cerebral blood flow responses evoked by SDs and provide critical 36 evidence that aging considerably weakens metabovascular coupling with SD. As a 37 consequence, the aged brain becomes increasingly more vulnerable to the deleterious effects 38 of SDs. 39 40