Published Online
on July 7, 2005

A more recent version of this article appeared on August 1, 2005

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Submitted on December 31, 2004
Accepted on January 28, 2005

Stroke-Induced Neurogenesis in Aged Brain

Vladimer Darsalia BSc; Ursula Heldmann MD; Olle Lindvall MD, PhD; and Zaal Kokaia PhD^*

From the Laboratory of Neural Stem Cell Biology (V.D., Z.K.) and the Laboratory of Neurogenesis and Cell Therapy (U.H., O.L.), Section of Restorative Neurology, University Hospital, and the Lund Strategic Research Center for Stem Cell Biology and Cell Therapy (V.D., U.H., O.L., Z.K.), Lund, Sweden.

^* To whom correspondence should be addressed. E-mail: zaal.kokaia{at}neurol.lu.se.

Background and Purpose--Stroke induced by middle cerebral artery occlusion (MCAO) triggers increased neurogenesis in the damaged striatum and nondamaged hippocampus of young adult rodents. We explored whether stroke influences neurogenesis similarly in the aged brain.

Methods--Young adult (3 months) and old (15 months) rats were subjected to 1 hour of MCAO, and new cells were labeled by intraperitoneal injection of 5-bromo-2'-deoxyuridine 5'-monophosphate (BrdU), a marker for dividing cells, for 2 weeks thereafter. Animals were euthanized at 7 weeks after the insult, and neurogenesis was assessed immunocytochemically with antibodies against BrdU and neuronal markers with epifluorescence or confocal microscopy.

Results--Young and old rats exhibited the same increased numbers of new striatal neurons after stroke, despite basal cell proliferation in the subventricular zone being reduced in the aged brain. In contrast, both the number of stroke-generated granule cells and basal neurogenesis in the dentate subgranular zone were lower in old compared with young animals. Also, the ability of newly formed cells to differentiate into neurons was impaired in the aged dentate gyrus.

Conclusions--Basal neurogenesis is impaired in the subgranular and subventricular zones of aged animals, but both regions react to stroke with increased formation of new neurons. The magnitude of striatal neurogenesis after stroke is similar in young and old animals, indicating that this potential mechanism for self-repair also operates in the aged brain.

Key words: cerebral arteries • hippocampus • ischemia • neuronal plasticity • stem cells • stroke, ischemic

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