Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Exploring the relationship between neuroinflammation and neurotoxicity.

Kelly-KA; Miller-DB; O'Callaghan-JP
Toxicologist 2014 Mar; 138(1):186-187
The enhanced expression of proinflammatory cytokines and chemokines accompanies brain injury induced by neurotrauma, disease or neurotoxicity as well as systemic infection. Elevations in proinflammatory mediators may serve as modulators or mediators of astroglial and microglial activation, cellular responses associated with all types of brain injury and collectively referred to as neuroinflammation. The "acute phase" response to systemic inflammation also leads to upregulation of proinflammatory cytokines/chemokines in the brain in the absence of underling neural damage, responses thought to be mediated largely by microglia and that serve as the basis of "sickness behavior". Activated glia may have neuroprotective roles or may exacerbate neural damage. Exposure to the known dopaminergic damage followed by neuroinflammation. Genetic and pharmacological interventions have resulted in partial suppression of the neuroinflammatory responses to MPTP and METH without affecting neurotoxicity and gliosis. In an attempt to achieve a complete suppression of neuroinflammation, chronic exposure to corticosterone (CORT) was used. Surprisingly, mice treated with CORT exhibited an exaggerated neuroinflammatory response to METH coupled with potentiated neurotoxicity (loss of dopaminergic nerve terminal marker, tyrosine hydroxylase) and gliosis. As the levels of chronic CORT approached or exceeded those associated with high physiological stress, the data suggest chronic CORT therapy or sustained physiological stress sensitizes CNS neuroinflammatory and neurotoxic responses. Yet, in a model of LPS-induced systemic infection that does not induce gliosis or neural damage, chronic CORT pretreatment greatly exacerbated and prolonged neuroinflammation without evidence of neural damage or gliosis. These results show a priming of the CNS proinflammatory response to amplify future exposures to pathogens, injury or toxicity. Taken together these findings suggest that while neurotoxicity causes inflammation, neuroinflammation may potentiate, but does not necessarily cause, neurotoxicity.
Toxicology; Cell-function; Cellular-function; Cell-damage; Exposure-levels; Pathology; Humans; Men; Women; Biomarkers; Risk-factors; Nervous-system; Neurotoxicology; Immunology; Immune-system; Pathogenesis; Diseases; Neurotoxins; Animal-studies; Brain-function; Traumatic-injuries; Brain-damage
Publication Date
Document Type
Fiscal Year
NTIS Accession No.
NTIS Price
Identifying No.
Issue of Publication
NIOSH Division
Source Name
The Toxicologist. Society of Toxicology 53rd Annual Meeting and ToxExpo, March 23-27, 2014, Phonex, Arizona