Artikel
Hippocampal neurogenesis is correlated to improved cognitive recovery after experimental traumatic brain injury and is further enhanced by S100B
Die hippocampale Neurogenese korreliert mit der Erholung kognitiver Funktionen nach experimentellem Schädel-Hirn-Trauma und wird verstärkt durch S100B
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Autoren
Veröffentlicht: | 4. Mai 2005 |
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Gliederung
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Objective
The neurotrophic protein S100B has been found to be released by astrocytes following stretch-injury, and S100B serum and CSF levels are elevated after traumatic brain injury (TBI) in humans. Since S100B has been shown to improve memory function, we examined whether an intraventricular S100B infusion enhances neurogenesis within the hippocampus following experimental TBI and whether the biological response can be associated with a measurable cognitive improvement.
Methods
Following lateral fluid percussion or sham injury in male rats (n=60), we infused S100B (50ng/hr) or vehicle into the lateral ventricle for 7 days using an osmotic micro-pump. Cell proliferation was assessed by injecting the mitotic marker Bromodeoxyuridine (BrdU) on day 2 post-injury. Differentiation of proliferating cells was demonstrated by co-labelling with neuronal and glial-specific markers and spatial learning ability was assessed by the Morris water maze.
Results
Quantification of BrdU-immunoreactive cells in the dentate gyrus revealed an increased progenitor cell proliferation as assessed on day 5 post-injury (p<0.05) and persisting up to 5 weeks (p<0.05). The percentage of brain stem cells differentiating into neurons correlated to an improved cognitive performance on day 30-34 post-injury (p<0.05). The enhanced hippocampal neurogenesis following TBI was profoundly increased by S100B (p<0.05) .
Conclusions
Collectively, our findings indicate that neurogenesis within the hippocampus can be correlated with an improved cognitive recovery following experimental TBI, and that an intraventricular S100B infusion enhances these endogenous repair mechanisms further. These observations provide compelling evidence for the therapeutic potential of S100B in improving functional recovery following TBI.