Research article summary (published 8 Mar 2009):

Post-ischemic hypothermia attenuates loss of the vascular basement membrane proteins, agrin and SPARC, and the blood-brain barrier disruption after global cerebral ischemia.

Full Abstract

Vascular basement membrane (BM) stabilizes brain vessels and inhibits endothelial cell cycle. Cerebral ischemia causes BM breakdown with the loss of structural BM components including collagens and laminins. In this study, the expression changes of the BM proteoglycan agrin, and the non-structural BM constituent SPARC (BM-40, osteonectin), were studied in brain vessels after global cerebral ischemia. A transient 20-min forebrain ischemia followed by 1, 6 or 24 h of reperfusion was induced in adult Sprague-Dawley rats by combined bilateral common carotid artery occlusion and hypotension (42-45 mm Hg). In a separate group of animals, a mild (32 degrees C) post-ischemic hypothermia was induced for 6 h, starting immediately after ischemia. RNA from approximately 500 brain vessels (20-100 microm) extracted by laser-capture microdissection (LCM) microscopy was used to determine the expression of proteoglycans agrin and SPARC mRNAs by quantitative PCR (Q-PCR). Protein expression was determined by immunohistochemistry in adjacent tissue sections. The BBB permeability was assessed using (3)H-sucrose as an in vivo tracer and by examining fibrinogen immunoreactivity in tissue sections. A transient global brain ischemia resulted in a significant (ANOVA, p<0.05; 6 animals/group) reduction in agrin and SPARC mRNAs in LCM-captured brain vessels 24 h after reperfusion. A time-dependent loss of agrin and SPARC from the BM during reperfusion was also observed by immunochemistry. A 6-h post-ischemic hypothermia reduced SPARC and agrin mRNA and protein losses, BBB transfer constant for (3)H-sucrose as well as fibrinogen extravasation 24 h after reperfusion. It is conluded that a transient post-ischemic hypothermia stabilizes brain vessels and reduces BBB disruption in part by preventing proteolytic degradation of regulatory BM constituents, SPARC and agrin.

Author information

Author/s: Baumann, Ewa (E); Preston, Edward (E); Slinn, Jacqueline (J); Stanimirovic, Danica (D);

Affiliation: Cerebrovascular Research Group, Institute for Biological Sciences, National Research Council of Canada, 1200 Montreal Road, Ottawa, Ontario, Canada.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Brain research (Brain Res), published in Netherlands. (Language: eng)

Reference: 2009-May; vol 1269 (issue ) : pp 185-97

Dates: Created 2009/05/01; Completed 2009/07/29;

PMID: 19285050, status: MEDLINE (last retrieval date: 8/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - genetics; metabolism Animals Basement Membrane - pathology; physiology Blood-Brain Barrier - pathology; physiology Brain - blood supply; pathology; physiology Brain Ischemia - pathology; therapy Female Fibrinogen - metabolism Hypothermia, Induced

Hypothermia, Induced Laminin - metabolism Male Osteonectin - genetics; metabolism RNA, Messenger - metabolism Rats Rats, Sprague-Dawley Sucrose - pharmacokinetics Tritium - diagnostic use

Associated Chemicals: Agrin (0) ; Laminin (0) ; Osteonectin (0) ; RNA, Messenger (0) ; Tritium (10028-17-8) ; Sucrose (57-50-1) ; Fibrinogen (9001-32-5)

Related articles

These are the highest related articles currently in the database:

• Ischemic neuronal damage. How does mild hypothermia modulate it? 29 Apr 1996
• Post-ischemic hypothermia ameliorates ischemic brain damage but not post-ischemic audiogenic seizures in rats. 30 Jul 1995
• Agrin accumulates in the brain microvascular basal lamina during development of the blood-brain barrier. 30 Dec 1996
• Regional variation in brain capillary density and vascular response to ischemia. 8 Aug 2001
• Combined treatment of vascular endothelial growth factor and human neural stem cells in experimental focal cerebral ischemia. 26 Sep 2005
• In vitro models of the blood-brain barrier to polar permeants: comparison of transmonolayer flux measurements and cell uptake kinetics using cultured cerebral capillary endothelial cells. 30 May 1999
• Microvascular basal lamina antigen loss after traumatic brain injury in the rat. 30 Jul 2003
• Nutrient consumption and metabolic perturbations. 30 Mar 1997
• Delayed postconditionig initiates additive mechanism necessary for survival of selectively vulnerable neurons after transient ischemia in rat brain. 11 Apr 2006
• Mild hypothermia: therapeutic window after experimental cerebral ischemia. 28 Feb 1996

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.