Lazovic, Jelena and Basu, Anirban and Lin, Hsiao Wen and Rothstein, Raymond P and Krady, J Kyle and Smith, Michael B and Levison, Steven W (2005) Neuroinflammation and Both Cytotoxic and Vasogenic Edema Are Reduced in Interleukin-1 Type 1 Receptor-Deficient Mice Conferring Neuroprotection. Stroke, 36. pp. 2226-2231.

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Abstract

Background and Purpose—Interleukin-1 (IL-1) is a proinflammatory cytokine implicated in multiple neurodegenerative diseases, including stroke. However, to date, there is no consensus regarding which receptor(s) mediates the detrimental effects of IL-1. We hypothesized that abrogating IL-1 type 1 receptor (IL-1R1) signaling would reduce edema, chemokine expression, and leukocyte infiltration; lower levels of iNOS; and, consequently, decrease free radical damage after mild hypoxia/ischemia (H/I), thus preserving brain cells. Methods—IL-1R1 null mice and wild-type mice were subjected to a mild H/I insult. MRI was used to measure the area affected at 30 minutes and 48 hours after H/I. An RNAse protection assay was used to evaluate changes in chemokine mRNA expression. RT-PCR was used to assess inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase mRNA levels. Immunohistochemistry was used to assess leukocyte infiltration. Western blots were used to assess iNOS and glutamate aspartate transporter protein levels. Results—IL-1R1 null mice had reduced cytotoxic and vasogenic edema. The volume of hyperintense signal on T2-weighted images was reduced on average by 90% at 48 hours after H/I. The induction of multiple chemokine mRNAs was significantly reduced in IL-1R1 null mice compared with wild-type mice at 18 and 72 hours after H/I, which correlated with fewer infiltrating CD3� leukocytes. Levels of iNOS protein and mRNA (but not glutamate aspartate transporter) were significantly reduced in the IL-1R1 mouse brain

Item Type:	Article
Subjects:	Neurodegenerative Disorders Neuro-Oncological Disorders Neurocognitive Processes Neuronal Development and Regeneration Informatics and Imaging Genetics and Molecular Biology
Depositing User:	Dr. D.D. Lal
Date Deposited:	05 Feb 2020 12:09
Last Modified:	13 Dec 2021 04:43
URI:	http://nbrc.sciencecentral.in/id/eprint/556

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