Age exaggerates proinflammatory cytokine signaling and truncates signal transducers and activators of transcription 3 signaling following ischemic stroke in the rat.
Dinapoli-VA; Benkovic-SA; Li-X; Kelly-KA; Miller-DB; Rosen-CL; Huber-JD; O'Callaghan-JP
Neuroscience 2010 Oct; 170(2):633-644
Neuroinflammation is associated with glial activation following a variety of brain injuries, including stroke. While activation of perilesional astrocytes and microglia following ischemic brain injury is well documented, the influence of age on these cellular responses after stroke is unclear. This study investigated the influence of advanced age on neuronal degeneration, neuroinflammation, and glial activation in female Sprague-Dawley rats after reversible embolic occlusion of the middle cerebral artery (MCAO). Results indicate that in comparison to young adult rats (3 months), aged rats (18 months) showed enhanced neuronal degeneration, altered microglial response, and a markedly increased expression of proinflammatory cytokines/chemokines following MCAO. In addition, the time-course for activation of signal transducers and activators of transcription 3 (STAT3), the signaling mechanism that regulates astrocyte reactivity, was truncated in the aged rats after MCAO. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3), which is associated with termination of astrogliosis, was enhanced as a function of age after MCAO. These findings are suggestive of an enhanced proinflammatory response and a truncated astroglial response as a function of advanced age following MCAO. These data provide further evidence of the prominent role played by age in the molecular and cellular responses to ischemic stroke and suggest that astrocytes may represent targets for future therapies aimed at improving stroke outcome.
Brain-damage; Brain-function; Injuries; Age-factors; Animals; Neurological-diseases; Neurological-system; Central-nervous-system-disorders; Central-nervous-system; Laboratory-animals; Animal-studies;
Author Keywords: astrocyte; microglia; middle cerebral artery occlusion; suppressor of cytokine signaling 3; interleukin 6; neuroinflammation
J.D. Huber, Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA
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