Aktuelle Neurologie 2004; 31 - P296
DOI: 10.1055/s-2004-833159

Premature appearance of proliferating cells in the aged rat brain following stroke

A Popa-Wagner 1, I Badan 1, I Dinca 1, Y Suofu 1, L Walker 1, C Kessler 1
  • 1(Greifswald)

Background and Purpose: The age-related decline in plasticity of the rodent brain may be associated with decreased rate of neurogenesis. Since aging is both a risk factor for stroke and an impediment to recovery, we studied cellular and genetic events associated with neurogenesis after stroke in young and aged rats.

Methods: 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 the functional outcome was studied at 3-, 7-, 14- and 28 days after surgery using a variety of neurological and behavioral tests. At each time point, brains were removed, sectioned and immunostained for the microglial marker ED-1, the astrocytic marker glial fibrillary acidic protein (GFAP), the endothelial cell marker, RECA, the dividing cell marker, BrdU as well as the stem cell marker, nestin and doublecortin.

Results:(i) Infarct development in young rat was slow and could be explained by the phenomenon of delayed neuronal death; vulnerability of the brain tissue to cerebral ischaemia rises with increasing age; (ii) apoptosis does not play a major role for the cell death in this model; (iii) we noted increased cerebrovascular permeability at the blood brain barrier (BBB). A 3D reconstruction of BrdU cells in the infarcted area of aged revealed that most of the BrdU cells either derived from the vasculature, that has been stained with the endothelial cell marker, RECA, or leaked in from the circulation. (iv) BrdU immunocytochemistry revealed numerous cells in the periventricular zone of both young and aged rats that appeared to be migrating from the periventricular zone into the corpus callosum. Some of these cells co-localized at day 3 with nestin, a marker for immature neurons both in young and notably in aged rats, also. However, while neurogenesis persists in young rats the number of BrdU cells co-localizing with nestin rapidly disappeared.

Conclusion: We conclude that aged rats mount a neurogenic response to ischemic damage that is only transient in nature and most newly neuroepithelial cells will become incoporated into blood vessels at the infarct border.