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In this malaria study, TNF-alpha levels were found to be significantly elevated in the cerebrospinal fluid of children with cerebral malaria, in comparison with controls. The authors discussed the need for a selective, CNS-active, anti-TNF treatment modality.
Excess TNF-alpha has also been documented in traumatic brain injury[1], spinal cord injury[2-4], neuropathic pain[5, 6], frontotemporal dementia[7], sleep apnea[8], stroke[9, 10] and Alzheimer’s disease[11-15].
Excess TNF implicated in additional brain disorders
A recent study from researchers at the University of Minnesota and the International Neurologic and Psychiatric Epidemiology Program highlights the significance of the signalling molecule, TNF-alpha, in the regulation of brain function across a variety of different illnesses, in this case malaria in Ugandan children. AlzheimerVideoNews.com has previously discussed the accumulating scientific evidence which suggests that excess TNF-alpha plays a central role in the pathogenesis of Alzheimer’s disease. In this malaria study, TNF-alpha levels were found to be significantly elevated in the cerebrospinal fluid of children with cerebral malaria, in comparison with controls. In addition, elevated CSF TNF-alpha was associated with subsequent neurologic and cognitive long-term morbidity. The authors discussed the need for a selective, CNS-active, anti-TNF treatment modality.
Excess TNF-alpha has also been documented in traumatic brain injury[1], spinal cord injury[2-4], neuropathic pain[5, 6], frontotemporal dementia[7], sleep apnea[8], stroke[9, 10] and Alzheimer’s disease[11-15]. These reports document the importance of consideration of TNF-alpha mediated pathophysiologic mechanisms and anti-TNF treatment strategies in each of these disorders. The diverse actions of TNF-alpha, with regard to not only initiation and amplification of the inflammatory response, but in regulation of both synaptic and vascular mechanisms, reflect the key role played by this pleiotropic signaling molecule in the physiology of both health and disease[16-19].
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2. Ferguson, A.R., R.N. Christensen, J.C. Gensel, B.A. Miller, F. Sun, et al., Cell death after spinal cord injury is exacerbated by rapid TNFalpha-induced trafficking of GluR2-lacking AMPARs to the plasma membrane. J Neurosci, 2008. 28(44): p. 11391-400.
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4. Marchand, F., C. Tsantoulas, D. Singh, J. Grist, A.K. Clark, et al., Effects of Etanercept and Minocycline in a rat model of spinal cord injury. Eur J Pain, 2008.
5. Sommer, C. and M. Schafers, Mechanisms of neuropathic pain: the role of cytokines. Drug Discovery Today: Disease Mechanisms, 2004. 1(4): p. 441-448.
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7. Sjogren, M., S. Folkesson, K. Blennow, and E. Tarkowski, Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications. J Neurol Neurosurg Psychiatry, 2004. 75(8): p. 1107-11.
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13. Ramos, E.M., M.T. Lin, E.B. Larson, I. Maezawa, L.H. Tseng, et al., Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch Neurol, 2006. 63(8): p. 1165-9.
14. Laws, S.M., R. Perneczky, S. Wagenpfeil, U. Muller, H. Forstl, et al., TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels. Hum Mutat, 2005. 26(1): p. 29-35.
15. Yang, L., R. Lu, L. Jiang, Z. Liu, and Y. Peng, Expression and genetic analysis of tumor necrosis factor-alpha (TNF-alpha) G-308A polymorphism in sporadic Alzheimer's disease in a Southern China population. Brain Res, 2008, epub ahead of print.
16. Clark, I.A., How TNF was recognized as a key mechanism of disease. Cytokine Growth Factor Rev, 2007. 18(3-4): p. 335-43.
17. Tobinick, E., Perispinal etanercept for neuroinflammatory disorders. Drug Discov Today, 2008, Nov 20, epub ahead of print.
18. Csiszar, A., N. Labinskyy, K. Smith, A. Rivera, Z. Orosz, et al., Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Am J Pathol, 2007. 170(1): p. 388-98.
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