Interleukin-1 Receptor 1 Deletion in Focal and Diffuse Experimental Traumatic Brain Injury in Mice

Journal of Neurotrauma
Joon Yong ChungMichael J Whalen

Abstract

Important differences in the biology of focal and diffuse traumatic brain injury (TBI) subtypes may result in unique pathophysiological responses to shared molecular mechanisms. Interleukin-1 (IL-1) signaling has been tested as a potential therapeutic target in preclinical models of cerebral contusion and diffuse TBI, and in a phase II clinical trial, but no published studies have examined IL-1 signaling in an impact/acceleration closed head injury (CHI) model. We hypothesized that genetic deletion of IL-1 receptor-1 (IL-1R1 KO) would be beneficial in focal (contusion) and CHI in mice. Wild type and IL-1R1 KO mice were subjected to controlled cortical impact (CCI), or to CHI. CCI produced brain leukocyte infiltration, HMGB1 translocation and release, edema, cell death, and cognitive deficits. CHI induced peak rotational acceleration of 9.7 × 105 ± 8.1 × 104 rad/s2, delayed time to righting reflex, and robust Morris water maze deficits without deficits in tests of anxiety, locomotion, sensorimotor function, or depression. CHI produced no discernable acute plasmalemma damage or cell death, blood-brain barrier permeability to IgG, or brain edema and only a modest increase in brain leukocyte infiltration at 72 h. In both models, ma...Continue Reading

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Citations

May 15, 2020·Advanced Healthcare Materials·Volha LiaudanskayaDavid L Kaplan
Feb 6, 2019·Frontiers in Neurology·Anelia A Y KassiShyam Gajavelli
Feb 11, 2020·Frontiers in Behavioral Neuroscience·Jason G ThomeMatthew J Robson
Aug 24, 2019·Frontiers in Cellular Neuroscience·Saef IzzyMichael J Whalen
Feb 16, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Limin WuJosephine Lok
Jun 8, 2021·Frontiers in Immunology·Colleen N BodnarAdam D Bachstetter

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Methods Mentioned

BETA
fluorescence activated cell sorting
enzymatic dissociation
gene knockout
ELISA
enzyme-linked immunosorbent assay
fluorescence activate cell sorting
FACS

Software Mentioned

GraphPad PRISM
ARRIVE
GraphPad
ImageJ

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