Aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-α levels following intracerebroventricular injection of lipopolysaccharide

A. N. Kalehua, D. D. Taub, P. V. Baskar, J. Hengemihle, J. Muñoz, M. Trambadia, D. L. Speer, M. G. De Simoni, D. K. Ingram

Research output: Contribution to journalArticle

Abstract

Background: Age-related defects in the development of peripheral inflammatory responses have been observed in rodents and humans. Objective: We examined the effects of age on a centrally injected endotoxin-induced cytokine production and cellular activation in mice. Methods: Male C57BL/6J (B6) mice, C3H/HeN mice, and C3H/HeJ mice received an intracerebroventricular injection of lipopolysaccharide (LPS) and were sacrificed at various times (2, 4, 8 h) thereafter. ELISA for IL-1β, IL-6, IL-12, and TNF-α were conducted on forebrain tissue homogenates as well as plasma samples, and lectin staining to detect activated microglia was prepared for selected brain slices. Results: Intracerebroventricular injection of LPS in B6 mice produced an age-associated increase in mortality which was paralleled with a significant increase in brain and plasma levels of TNF-α. Anti- TNF-α- and IL-6-immunoreactive cells possessed macrophagelike morphologies and were observed along the LPS injection tract and scattered throughout the hilus of the dorsal hippocampus and cerebral cortices. This LPS-mediated response was found to be specific in that the LPS-hyporesponsive mouse strain (C3H/HeJ) failed to demonstrate significant brain or plasma levels of TNF-α after LPS administration compared to C3H/HeN mice. Conclusion: These results suggest that the age-related increases in TNF-α production and mortality following the intracerebroventricular administration of LPS may be due to an increased endotoxin hypersensitivity of brain microglia/macrophages within aged animals. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)115-128
Number of pages14
JournalGerontology
Volume46
Issue number3
Publication statusPublished - 2000

Keywords

  • Aging
  • Cytokine
  • Endotoxin
  • Glia
  • Interleukins
  • Neuroinflammation

ASJC Scopus subject areas

  • Ageing

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    Kalehua, A. N., Taub, D. D., Baskar, P. V., Hengemihle, J., Muñoz, J., Trambadia, M., Speer, D. L., De Simoni, M. G., & Ingram, D. K. (2000). Aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-α levels following intracerebroventricular injection of lipopolysaccharide. Gerontology, 46(3), 115-128.