Effects of early aging and cerebral hypoperfusion on spreading depression in rats

Cortical spreading depression (CSD) is a feature of stroke pathophysiology. As stroke incidence increases with age, we have examined the effects of early aging and chronic cerebral hypoperfusion on CSD in rats. Three groups were studied: Young, 2-month-old animals; Middle-aged-2VO, subjected to 8 months of bilateral carotid occlusion from 2-month-of-age; and Middle-aged-SHAM, sham-operated. At 2- and 10-month-of-age for the Young and Middle-aged groups, recurrent CSD were induced under halothane anesthesia, by sustained application of 1 M KCl to the cortex for 2 h. Propagating CSD (i.e., cortical EEG, direct current potential) and associated laser Doppler blood flow changes were recorded anteriorly. Susceptibility to CSD and event duration were both decreased by early aging (frequency: 21±0.5 and 6±0.5 CSD/h; duration: 139±7 and 63±8 s; in Young and Middle-aged-SHAM, respectively). There was also a tendency for CSD-associated hyperemia to be reduced in the Middle-aged-2VO group (8.9±2.1 vs. 32.8±12.6% × min in Young). These data suggest reduced sensitivity of the cortex to CSD elicitation with early aging, and a less responsive cerebrovascular system with chronic hypoperfusion.