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Neurobiol Aging. 2015 Oct;36(10):2877-84. doi: 10.1016/j.neurobiolaging.2015.06.015. Epub 2015 Jun 18.

Inhibition of Tnf-α R1 signaling can rescue functional cortical plasticity impaired in early post-stroke period.

Author information

1
Department of Molecular and Cellular Neurobiology, Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address: m.liguz@nencki.gov.pl.
2
Department of Molecular and Cellular Neurobiology, Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, Warsaw, Poland.
3
Department of Molecular and Cellular Neurobiology, Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, Warsaw, Poland; University of Social Science and Humanities, Warsaw, Poland.

Abstract

Tumor necrosis factor-α (TNF-α) is one of the key players in stroke progression and can interfere with brain functioning. We previously documented an impairment of experience-dependent plasticity in the cortex neighboring the stroke-induced lesion, which was accompanied with an upregulation of Tnf-α level in the brain of ischemic mice 1 week after the stroke. Because TNF receptor 1 (TnfR1) signaling is believed to be a major mediator of the cytotoxicity of Tnf-α through activation of caspases, we used an anti-inflammatory intervention aimed at Tnf-α R1 pathway, in order to try to attenuate the detrimental effect of post-stroke inflammation, and investigated if this will be effective in protecting plasticity in the infarct proximity. Aged mice (12-14 months) were subjected to the photothrombotic stroke localized near somatosensory cortex, and immediately after ischemia sensory deprivation was introduced to induce plasticity. Soluble TNF-α R1 (sTNF-α R1), which competed for TNF-α with receptors localized in the brain, was delivered chronically directly into the brain tissue for the whole period of deprivation using ALZET Micro-Osmotic pumps. We have shown that such approach undertaken simultaneously with the stroke reduced the level of TNF-α in the peri-ischemic tissue and was successful in preserving the post-stroke deprivation-induced brain plasticity.

KEYWORDS:

Brain; Inflammation; Photothrombotic stroke; Plasticity; Tnf-α; sTNFα R1

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