Article
Histological characteristics of the hypothalamus after experimental traumatic brain injury
Morphologische Charakterisierung hypothalamischer Läsionen nach experimentellem SHT am Mausmodell
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Published: | April 11, 2007 |
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Objective: In the United States each year about half a million patients suffer from traumatic brain injury (TBI). Besides cognitive dysfunctions, hypopituitarism is a major complication- even in patients without any macroscopic damage to the pituitary. The aim of the present study was the examination of morphological changes by immuno-histochemistry of the hypothalamus and the hypothalamic-pituitary axis in correlation with the endocrine state in an experimental mouse model of TBI.
Methods: We investigated 16 mice with TBI after controlled cortical impact (CCI). Sixteen sham-operated mice served as a control group. Eight mice of each group were sacrificed after 15 and 30 days, respectively. Brains were removed, embedded in paraffin and cut in coronal sections. The hypothalamic area was investigated by immunhistochemistry using antibodies directed against cFos, GFAP, IBA-1, β-APP and by immunofluorescence using Fluoro-Jade.
Results: Using this approach we found a significant gliosis in injured animals when compared with controls. The number of GFAP-immunoreactive astrocytes was two times as high as in sham-operated animals both after 15 and 30 days. In addition, an intense activation of microglial cells could be demonstrated by immunostaining against the IBA-1 epitope. Neuronal and axonal damage could only sporadically be observed, but not to a significant degree. However, our data indicate reactive changes in the hypothalamus as a potential cause in the pathogenesis of hypopituitarism after TBI.
Conclusions: In conclusion, the demonstration of morphological alterations predominantly reactive changes in the hypothalamic region clearly indicate the suitability of the model of CCI for the investigation of endocrine disturbances after TBI. However, for investigation of neuronal changes a more widespread damage by experimental TBI like in the impact acceleration or diffuse injury model seems to be a more appropriate as it corresponds more with the human situation of accidental TBI.