Neutralization of interleukin-1 beta reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice
2011 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 34, no 1, 110-123 p.Article in journal (Refereed) Published
Increasing evidence suggests that interleukin-1 beta (IL-1 beta) is a key mediator of the inflammatory response following traumatic brain injury (TBI). Recently, we showed that intracerebroventricular administration of an IL-1 beta-neutralizing antibody was neuroprotective following TBI in mice. In the present study, an anti-IL-1 beta antibody or control antibody was administered intraperitoneally following controlled cortical injury (CCI) TBI or sham injury in 105 mice and we extended our histological, immunological and behavioral analysis. First, we demonstrated that the treatment antibody reached target brain regions of brain-injured animals in high concentrations (> 11 nm) remaining up to 8 days post-TBI. At 48 h post-injury, the anti-IL-1b treatment attenuated the TBI-induced hemispheric edema (P < 0.05) but not the memory deficits evaluated using the Morris water maze (MWM). Neutralization of IL-1 beta did not influence the TBI-induced increases (P < 0.05) in the gene expression of the Ccl3 and Ccr2 chemokines, IL-6 or Gfap. Up to 20 days post-injury, neutralization of IL-1 beta was associated with improved visuospatial learning in the MWM, reduced loss of hemispheric tissue and attenuation of the microglial activation caused by TBI (P < 0.05). Motor function using the rotarod and cylinder tests was not affected by the anti-IL-1 beta treatment. Our results suggest an important negative role for IL-1 beta in TBI. The improved histological and behavioral outcome following anti-IL-1 beta treatment also implies that further exploration of IL-1 beta-neutralizing compounds as a treatment option for TBI patients is warranted.
Place, publisher, year, edition, pages
2011. Vol. 34, no 1, 110-123 p.
behavior, cognition, edema, microglia, traumatic brain injury
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-156484DOI: 10.1111/j.1460-9568.2011.07723.xISI: 000292522400012OAI: oai:DiVA.org:uu-156484DiVA: diva2:431932