Vascular-Directed Responses of Microglia Produced by Methamphetamine Exposure: Indirect Evidence that Microglia Are Involved in Vascular Repair

Details

• Journal Article:
  J Neuroinflammation
• Personal Author:
  Bowyer, John F. ; Sarkar, Sumit ; Tranter, Karen M. ; Hanig, Joseph P. ; Miller, Diane B. ; O’Callaghan, James P.
• Description:
  Background
  
  Brain microglial activations and damage responses are most commonly associated with neurodegeneration or systemic innate immune system activation. Here, we used histological methods to focus on microglial responses that are directed towards brain vasculature, previously undescribed, after a neurotoxic exposure to methamphetamine.
  
  Methods
  
  Male rats were given doses of methamphetamine that produce pronounced hyperthermia, hypertension, and toxicity. Identification of microglia and microglia-like cells (pericytes and possibly perivascular cells) was done using immunoreactivity to allograft inflammatory factor 1 (Aif1 a.k.a Iba1) and alpha M integrin (Itgam a.k.a. Cd11b) while vasculature endothelium was identified using rat endothelial cell antigen 1 (RECA-1). Regions of neuronal, axonal, and nerve terminal degeneration were determined using Fluoro-Jade C.
  
  Results
  
  Dual labeling of vasculature (RECA-1) and microglia (Iba1) showed a strong association of hypertrophied cells surrounding and juxtaposed to vasculature in the septum, medial dorsal hippocampus, piriform cortex, and thalamus. The Iba1 labeling was more pronounced in the cell body while Cd11b more so in the processes of activated microglia. These regions have been previously identified to have vascular leakage after neurotoxic methamphetamine exposure. Dual labeling with Fluoro-Jade C and Iba1 indicated that there was minimal or no evidence of neuronal damage in the septum and hippocampus where many hypertrophied Iba1-labeled cells were found to be associated with vasculature. Although microglial activation around the prominent neurodegeneration was found in the thalamus, there were also many examples of activated microglia associated with vasculature.
  
  Conclusions
  
  The data implicate microglia, and possibly related cell types, in playing a major role in responding to methamphetamine-induced vascular damage, and possibly repair, in the absence of neurodegeneration. Identifying brain regions with hypertrophied/activated microglial-like cells associated with vasculature has the potential for identifying regions of more subtle examples of vascular damage and BBB compromise.
  
  Electronic supplementary material
  
  The online version of this article (doi:10.1186/s12974-016-0526-6) contains supplementary material, which is available to authorized users.
  
  
• Subjects:
  Animals Antigens, Surface Blood Vessels Calcium-Binding Proteins CD11b Antigen Central Nervous System Stimulants Membrane Glycoproteins Methamphetamine Microfilament Proteins Microglia Nerve Degeneration Neurotoxicity Syndromes Rats Rats, Sprague-Dawley Respiratory System Respiratory Tract Diseases

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• Keywords:
  Author Keywords: Microglia; Vascular Damage; Methamphetamine; Amphetamine; Neurotoxicity; Hyperthermia; Hypertension Neurological System; Brain Function; Neurotoxic Effects; Neurotoxicity; Exposure Levels; Risk Factors; Methamphetamine; Animals; Laboratory Animals; Hyperthermia; Hypertension; Toxic Effects; Endothelial Cells;
• Source:
  J Neuroinflammation. 13.
• Pubmed ID:
  26970737
• Pubmed Central ID:
  PMC4789274
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Arkansas ; Maryland ; OSHA Region 3 ; OSHA Region 6 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  15 pdf pages
• Volume:
  13
• Issue:
  1
• NIOSHTIC Number:
  nn:20047754
• Federal Fiscal Year:
  2016
• Peer Reviewed:
  True
• Collection(s):
  CDC Public Access National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1b22b9fbb64a25d833ef8d12cbe0db53d3c9ced27ef5f3e9196f852a6964039e1cd2f484f8828b796164a83bb1d2cd7b4ca0f4be96ccb4c7bd2e99a35b3f91cb
• Download URL:
  https://stacks.cdc.gov/view/cdc/38566/cdc_38566_DS1.pdf
• File Type:
  [PDF - 7.38 MB ]