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.