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Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP
by
Rosenberg, Gary A
, Roitbak, Tamara
, Thompson, Jeffrey F
, Jalal, Fakhreya Y
, Yang, Yi
in
Animals
/ Anti-Bacterial Agents - therapeutic use
/ Anti-Inflammatory Agents - therapeutic use
/ Blood-Brain Barrier - drug effects
/ Blood-Brain Barrier - immunology
/ Blood-Brain Barrier - pathology
/ Cerebrovascular Circulation - drug effects
/ Hypoxia - complications
/ Hypoxia - immunology
/ Hypoxia-Inducible Factor 1, alpha Subunit - analysis
/ Hypoxia-Inducible Factor 1, alpha Subunit - immunology
/ Inflammation - complications
/ Inflammation - drug therapy
/ Inflammation - immunology
/ Inflammation - pathology
/ Male
/ Matrix Metalloproteinase 2 - analysis
/ Matrix Metalloproteinase 2 - immunology
/ Matrix Metalloproteinase 9 - analysis
/ Matrix Metalloproteinase 9 - immunology
/ Minocycline - therapeutic use
/ Original
/ Rats
/ Rats, Inbred SHR
/ White Matter - drug effects
/ White Matter - immunology
/ White Matter - injuries
/ White Matter - pathology
2015
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Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP
by
Rosenberg, Gary A
, Roitbak, Tamara
, Thompson, Jeffrey F
, Jalal, Fakhreya Y
, Yang, Yi
in
Animals
/ Anti-Bacterial Agents - therapeutic use
/ Anti-Inflammatory Agents - therapeutic use
/ Blood-Brain Barrier - drug effects
/ Blood-Brain Barrier - immunology
/ Blood-Brain Barrier - pathology
/ Cerebrovascular Circulation - drug effects
/ Hypoxia - complications
/ Hypoxia - immunology
/ Hypoxia-Inducible Factor 1, alpha Subunit - analysis
/ Hypoxia-Inducible Factor 1, alpha Subunit - immunology
/ Inflammation - complications
/ Inflammation - drug therapy
/ Inflammation - immunology
/ Inflammation - pathology
/ Male
/ Matrix Metalloproteinase 2 - analysis
/ Matrix Metalloproteinase 2 - immunology
/ Matrix Metalloproteinase 9 - analysis
/ Matrix Metalloproteinase 9 - immunology
/ Minocycline - therapeutic use
/ Original
/ Rats
/ Rats, Inbred SHR
/ White Matter - drug effects
/ White Matter - immunology
/ White Matter - injuries
/ White Matter - pathology
2015
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Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP
by
Rosenberg, Gary A
, Roitbak, Tamara
, Thompson, Jeffrey F
, Jalal, Fakhreya Y
, Yang, Yi
in
Animals
/ Anti-Bacterial Agents - therapeutic use
/ Anti-Inflammatory Agents - therapeutic use
/ Blood-Brain Barrier - drug effects
/ Blood-Brain Barrier - immunology
/ Blood-Brain Barrier - pathology
/ Cerebrovascular Circulation - drug effects
/ Hypoxia - complications
/ Hypoxia - immunology
/ Hypoxia-Inducible Factor 1, alpha Subunit - analysis
/ Hypoxia-Inducible Factor 1, alpha Subunit - immunology
/ Inflammation - complications
/ Inflammation - drug therapy
/ Inflammation - immunology
/ Inflammation - pathology
/ Male
/ Matrix Metalloproteinase 2 - analysis
/ Matrix Metalloproteinase 2 - immunology
/ Matrix Metalloproteinase 9 - analysis
/ Matrix Metalloproteinase 9 - immunology
/ Minocycline - therapeutic use
/ Original
/ Rats
/ Rats, Inbred SHR
/ White Matter - drug effects
/ White Matter - immunology
/ White Matter - injuries
/ White Matter - pathology
2015
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Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP
Journal Article
Hypoxia-Induced Neuroinflammatory White-Matter Injury Reduced by Minocycline in SHR/SP
2015
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Overview
Hypertensive small vessel disease is a major cause of vascular cognitive impairment (VCI). Spontaneously hypertensive/stroke prone rats (SHR/SP) with unilateral carotid artery occlusion (UCAO) and a Japanese permissive diet (JPD) have white-matter (WM) damage similar to that seen in VCI. We hypothesized that WM injury was due to hypoxia-mediated, blood–brain barrier (BBB) disruption. Twelve-week-old SHR/SP had UCAO/JPD and were studied with immunohistochemistry, biochemistry, multimodal magnetic resonance imaging (MRI), and Morris water maze (MWM) testing. One week after UCAO/JPD, WM showed a significant increase in hypoxia inducible factor-1α (HIF-1α), which increased further by 3 weeks. Prolyl hydroxylase-2 (PHD2) expression decreased at 1 and 3 weeks. Infiltrating T cells and neutrophils appeared around endothelial cells from 1 to 3 weeks after UCAO/JPD, and matrix metalloproteinase-9 (MMP-9) colocalized with inflammatory cells. At 3 weeks, WM immunostained for IgG, indicating BBB leakage. Minocycline (50 mg/kg intraperitoeally) was given every other day from weeks 12 to 20. Multimodal MRI showed that treatment with minocycline significantly reduced lesion size and improved cerebral blood flow. Minocycline improved performance in the MWM and prolonged survival. We propose that BBB disruption occurred secondary to hypoxia, which induced an MMP-9-mediated infiltration of leukocytes. Minocycline significantly reduced WM damage, improved behavior, and prolonged life.
Publisher
SAGE Publications,Sage Publications Ltd,Nature Publishing Group
Subject
/ Anti-Bacterial Agents - therapeutic use
/ Anti-Inflammatory Agents - therapeutic use
/ Blood-Brain Barrier - drug effects
/ Blood-Brain Barrier - immunology
/ Blood-Brain Barrier - pathology
/ Cerebrovascular Circulation - drug effects
/ Hypoxia-Inducible Factor 1, alpha Subunit - analysis
/ Hypoxia-Inducible Factor 1, alpha Subunit - immunology
/ Inflammation - complications
/ Male
/ Matrix Metalloproteinase 2 - analysis
/ Matrix Metalloproteinase 2 - immunology
/ Matrix Metalloproteinase 9 - analysis
/ Matrix Metalloproteinase 9 - immunology
/ Minocycline - therapeutic use
/ Original
/ Rats
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