Spreading depolarization in the ischemic brain: does aging have an impact?

Recurrent waves of spreading depolarization (SD) spontaneously occur minutes after the onset of focal ischemia in the brain and keep generating for a number of days to follow. It has become widely accepted that ischemia-related SDs are part of the pathophysiology of cerebrovascular diseases and predict worse outcome. SDs may exacerbate ischemic injury via related atypical hemodynamic responses. The incidence of ischemic stroke is known to increase markedly with age; yet, very few studies investigated whether age alters SD evolution and whether a potential age-specific pattern of SD would contribute to the age-related intensification of infarct development. Experimental data demonstrate that aging has a marked impact on SD evolution and corresponding changes in cerebral blood flow. We hypothesize that an age-specific pattern of the SD-associated hemodynamic response must be involved in augmenting the expansion of ischemic brain damage in the elderly patients and that structural and functional (mal)adaptation of the cerebrovascular system with aging serves as a potential basis for compromised vascular reactivity and subsequent tissue damage. The concept put forward is expected to stimulate further investigation to achieve a comprehensive overview of the implication of SD in injury progression in the aged brain.