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Increased levels of TNFα but not TGBβ1 are associated with the severity of congenital hydrocephalus in the hyh mouse
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Neuropathology and Applied Neurobiology
- Accepted manuscript online: 26 DEC 2013 03:11AM EST
- Manuscript Accepted: 20 DEC 2013
- Cited By
- congenital hydrocephalus;
- reactive astrocyte;
Here, we tested the hypothesis that glial responses via the production of cytokines such as transforming growth factor-beta 1 (TGFb1) and tumour necrosis factor alpha (TNFa), which play important roles in neurodegenerative diseases, are correlated with the severity of congenital hydrocephalus in the hyh mouse model. We also searched for evidence of this association in human cases of primary hydrocephalus.
Hyh mice, which exhibit either severe or compensated long-lasting forms of hydrocephalus, were examined and compared with wild-type mice. TGFb1, TNFa and TNFaR1 mRNA levels were quantified using real-time PCR. TNFa and TNFaR1 were immunolocalised in the brain tissues of hyh mice and four hydrocephalic human fetuses relative to astroglial and microglial reactions.
The TGFb1 mRNA levels were not significantly different between hyh mice exhibiting severe or compensated hydrocephalus and normal mice. In contrast, severely hydrocephalic mice exhibited four- and two-fold increases in the mean levels of TNFa and TNFaR1, respectively, compared with normal mice. In the hyh mouse, TNFa and TNFaR1 immunoreactivity was preferentially detected in astrocytes that form a particular periventricular reaction characteristic of hydrocephalus. However, these proteins were rarely detected in microglia, which did not appear to be activated. TNFa immunoreactivity was also detected in the glial reaction in the small group of human fetuses exhibiting hydrocephalus that were examined.
In the hyh mouse model of congenital hydrocephalus, TNFa and TNFaR1 appear to be associated with the severity of the disease, probably mediating the astrocyte reaction, neurodegenerative processes and ischaemia.