Artikel
The improved cognitive recovery after fluid percussion injury by intraventricular S100B infusion is associated with enhanced hippocampal neurogenesis
Die verbesserte Erholung kognitiver Funktionen nach experimentellem Schädelhirntrauma durch S100B-Infusion ist assoziiert mit vermehrter Stammzellproliferation und neuronaler Differenzierung im Hippocampus
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Autoren
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Andrea Kleindienst
- Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond /USA
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M. McGinn
- Department of Anatomy and Neurobiology, Medical College of Virginia, Virginia Commonwealth University, Richmond /USA
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A. C. Rice
- Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond /USA
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H. B. Harvey
- Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond /USA
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R. J. Hamm
- Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond /USA
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M. R. Bullock
- Department of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, Richmond /USA
| Veröffentlicht: | 23. April 2004 |
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Gliederung
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Objective
Recent evidence of injury induced neuro- and gliagenesis in the adult hippocampus suggests an endogenous repair mechanism for cognitive dysfunction following traumatic brain injury (TBI). S100B is a calcium-binding protein mainly produced by astrocytes that exerts auto- and paracrine effects on glia respectively neurons, thereby stimulating cell proliferation and differentiation. As improved cognitive function has been found after S100B infusion, we examined whether this is associated with enhanced hippocampal cell proliferation and differentiation after experimental TBI.
Methods
Following lateral fluid percussion or sham injury in male Sprague Dawley rats (n=60), we infused S100B (50ng/hr) or vehicle into the cerebrospinal fluid of the ipsilateral ventricle for 7d using an osmotic mini-pump. Cell proliferation was assessed after injection of 5-Bromo-2’-deoxyuridine (BrdU), a marker of S-phase mitosis, on day 2 post-injury with consecutive quantification of BrdU immunoreactive cells in the sub-ventricular zone and in the dentate gyrus on day 5 or 34, and double-labeling with the glial marker GFAP or the neuronal marker NeuN on day 34. Spatial learning ability was assessed by the Morris water maze on day 30-34 after injury.
Results
Quantification of BrdU immunoreactive cells revealed an increased proliferative response after TBI in the S100B infused animals (p<0.05)., while double-labeling demonstrated the proliferating cells in the dentate gyrus to express predominately NeuN after S100B infusion (p<0.05). The cognitive performance was improved after S100B infusion (p<0.05), when compared to vehicle infusion.
Conclusions
Our findings indicate that neurogenesis within the hippocampus after S100B infusion is linked to an improved cognitive recovery following TBI. The exact molecular mechanisms by which the S100B protein exerts its neurotrophic influence and contributes to functional recovery after TBI need to be elucidated further.
