Postischemic housing in an enriched environment influences hippocampal progenitor cell differentiation after focal cortical ischemia

• We have tested the hypothesis that environmental factors can influence postischemic progenitor cell survival and differentiation in the dentate gyrus. The proliferation marker bromodeoxyuridine (BrdU) was administered during 7 days starting 24 h after ligation of the right middle cerebral artery. Postoperatively the rats were housed in standard cages or transferred to enriched environment 24 h or 7 days after the ligation. Rats housed in standard cages performed significantly worse than rats housed in an enriched environment in a leg placement and a rotating pole test four weeks after the arterial ligation. Neurogenesis and gliogenesis were determined by triple labeling with antibodies against BrdU, the astrocytic marker glial fibrillary acidic protein (GFAP), and the neuronal markers Calbindin D28k and NeuN. Rats with cortical lesions had a 5- to 6-fold increase in BrdU labeled cells on the ipsilateral side (p<0.001 for the delayed enriched group; p<0.01 for the early enriched and standard groups) and a 2- to 3-fold non-significant increase on the contralateral side with no significant differences between the groups. About 80% of the BrdU-positive cells co-labeled with NeuN and about 70% of the BrdU-positive cells co-labeled with Calbindin D28K. Although housing conditions did not influence neurogenesis it markedly altered gliogenesis. Whereas the standard group did not have more astrocytes than sham-operated rats on the ipsilateral side, the early and delayed enriched group had a 3- to 5-fold increase, respectively, thereby normalizing the severely disturbed neuron to glia ratio in the standard group. We hypothesize that the newly formed neurons in the standard group would have a poor environment in the absence of a concomitant gliogenesis. Astrocytes play an important role in neuronal plasticity, and we propose that more attention should be given to gliogenesis in experimental studies on cell proliferation and differentiation after brain lesions.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Nyckelord

neurogenesis

glial fibrillary acidic protein (GFAP)

ischemia

focal brain

enriched environment

bromodeoxyuridine (BrdU)

calbinin

stem cells

rat

progenitor cells

gliogenesis

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kon (ämneskategori)

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