Accelerated infarct development, cytogenesis and apoptosis following cerebral ischaemia in aged rats

Background and purpose: Old age is associated with an enhanced susceptibility to stroke and deficient recovery from brain injury, but the cellular mechanisms underlying such phenomena are poorly understood.

Methods: To address this issue, focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3 month- and 20 month-old male Sprague Dawley rats and brains analyzed by BrdU-labeling, quantitative immunohistochemistry and 3D-reconstruction of confocal images.

Results: We found that aged rats are predisposed to rapidly develop an infarct within the first few days after ischemia. The emergence of the necrotic zone is associated with a high degeneration rate, premature accumulation of proliferating BrdU-positive cells that appear to emanate from capillaries into the infarcted area and a high number of apoptotic cells. Other identified BrdU-positive cells at the infarct site in both age groups were reactive microglia, oligodendrocytes and astrocytes and to a lesser extent, CD8+ cells. Paradoxically, despite of a vigorous reactive phenotype of microglia and astrocytes in aged rats, at one week post-stroke, the number of proliferating microglia and astrocytes was lower in aged rats than in young rats.

Conclusions: Our data indicate that aging is associated with an increased susceptibility to stroke possibly due to premature cellular proliferation and to an increased number of degenerating and apoptotic cells in the infarcted area and points to an hitherto unrecognized role of the vasculature for infarct progression in aged rats.