Age exaggerates proinflammatory cytokine signaling and truncates signal transducers and activators of transcription 3 signaling following ischemic stroke in the rat

Details

• Personal Author:
  Benkovic SA ; Dinapoli VA ; Huber JD ; Kelly KA ; Li X ; Miller DB ; O'Callaghan JP ; Rosen CL
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Age Factors Animals Laboratories Nervous System Nervous System Diseases Nervous System Disorders Occupational Health Safety
• Keywords:
  Age-factors Animal-studies Author Keywords: Astrocyte Brain-damage Brain-function Central-nervous-system Central-nervous-system-disorders Injuries Interleukin 6 Laboratory-animals Microglia Middle Cerebral Artery Occlusion Neuroinflammation Neurological-diseases Neurological-system Suppressor Of Cytokine Signaling 3

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• ISSN:
  0306-4522
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  170
• Issue:
  2
• NIOSHTIC Number:
  nn:20037747
• Citation:
  Neuroscience 2010 Oct; 170(2):633-644
• Contact Point Address:
  J.D. Huber, Department of Basic Pharmaceutical Sciences, West Virginia University School of Pharmacy, Morgantown, WV 26506, USA
• Email:
  jhuber@hsc.wvu.edu
• Federal Fiscal Year:
  2011
• NORA Priority Area:
  Healthcare and Social Assistance ; Transportation, Warehousing and Utilities
• Peer Reviewed:
  True
• Source Full Name:
  Neuroscience
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:42642f00d93a9c122427d519192f6aae7eaae1ab5276e02c5828cdbf212731761a188ed26defcd24c31f7b39d1f32a1705adb527fecef26868841fe7bd5814f1
• Download URL:
  https://stacks.cdc.gov/view/cdc/191733/cdc_191733_DS1.pdf
• File Type:
  [PDF - 3.97 MB ]