title: Inhibition of Tnf-α R1 signaling can rescue functional cortical plasticity impaired in early post-stroke period.
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.
authors.affiliation: Department of Molecular and Cellular Neurobiology, Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, Warsaw, Poland. Electronic address: m.liguz@nencki.gov.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Liguz-Lecznar
authors.affiliation: Department of Molecular and Cellular Neurobiology, Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, Warsaw, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Zakrzewska
authors.affiliation: Department of Molecular and Cellular Neurobiology, Laboratory of Neuroplasticity, Nencki Institute of Experimental Biology, Warsaw, Poland; University of Social Science and Humanities, Warsaw, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kossut
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D007260:Infusion Pumps; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy; D009473:Neuronal Plasticity / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000008:administration & dosage* / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D013003:Somatosensory Cortex / Q000503:physiopathology*; D020521:Stroke / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha
keywords: Brain; Inflammation; Photothrombotic stroke; Plasticity; Tnf-α; sTNFα R1