Background Tumor necrosis factor (TNF)-α has been suggested to play both a deleterious and beneficial role in neurobehavioral dysfunction and recovery following traumatic brain injury (TBI). The goal of this study was to evaluate the specific role of tumor necrosis factor (TNF) receptors p55 and p75 in mediating cognitive outcome following controlled cortical impact (CCI) brain injury by comparing post-traumatic cognitive function in mice with genetically engineered deletion of the gene for either p55 (−/−) or p75 (−/−) receptors.
Method Male C57Bl/6 mice (WT, n=29), and mice genetically engineered to delete p55 TNF (p55 (-/-), n=8) or p75 TNF (p75 (−/−), n=23) receptors were used. They were anesthetized with intraperitoneal (i.p.) administration of sodium pentobarbital (65 mg/kg) and subjected to CCI brain injury of moderate severity. Sham-injured control mice were anesthetized and surgically prepared similarly but they received no impact. Assessment of mRNA expression of inflammatory, proapoptotic and antiapoptotic genes was done by real time-polymerase chain reaction (RT-PCR). Cognitive outcome was evaluated at 4 weeks postinjury using the Morris water maze (MWM).
Findings mRNA expression of inflammatory, proapoptotic and antiapoptotic genes prior to TBI did not reveal any baseline difference between p55 and p75 (−/−) mice. WT mice showed greater baseline expression of inflammatory genes. The learning ability of p55 (−/−) brain-injured mice was significantly better than that observed in p75 (−/−) brain-injured mice (p<0.05). Cognitive learning in WT control mice fell between the p55 (−/−) and p75 (−/−) mice.
Conclusions These data suggest that TNF-α may both exacerbate cognitive dysfunction via p55 receptor and attenuate it via p75 receptor.
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Longhi, L., Ortolano, F., Zanier, E.R., Perego, C., Stocchetti, N., De Simoni, M.G. (2008). Effect of traumatic brain injury on cognitive function in mice lacking p55 and p75 tumor necrosis factor receptors. In: Steiger, H.J. (eds) Acta Neurochirurgica Supplements. Acta Neurochirurgica Supplementum, vol 102. Springer, Vienna. https://doi.org/10.1007/978-3-211-85578-2_80
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