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Published Online: 30 January 2012

Ghrelin Prevents Disruption of the Blood–Brain Barrier after Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 29, Issue Number 2

Abstract

Significant effort has been focused on reducing neuronal damage from post-traumatic brain injury (TBI) inflammation and blood–brain barrier (BBB)-mediated edema. The orexigenic hormone ghrelin decreases inflammation in sepsis models, and has recently been shown to be neuroprotective following subarachnoid hemorrhage. We hypothesized that ghrelin modulates cerebral vascular permeability and mediates BBB breakdown following TBI. Using a weight-drop model, TBI was created in three groups of mice: sham, TBI, and TBI/ghrelin. The BBB was investigated by examining its permeability to FITC-dextran and through quantification of perivascualar aquaporin-4 (AQP-4). Finally, we immunoblotted for serum S100B as a marker of brain injury. Compared to sham, TBI caused significant histologic neuronal degeneration, increases in vascular permeability, perivascular expression of AQP-4, and serum levels of S100B. Treatment with ghrelin mitigated these effects; after TBI, ghrelin-treated mice had vascular permeability and perivascular AQP-4 and S100B levels that were similar to sham. Our data suggest that ghrelin prevents BBB disruption after TBI. This is evident by a decrease in vascular permeability that is linked to a decrease in AQP-4. This decrease in vascular permeability may diminish post-TBI brain tissue damage was evident by decreased S100B.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 29Issue Number 2January 20, 2012
Pages: 385 - 393
PubMed: 21939391

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Published online: 30 January 2012
Published in print: January 20, 2012
Published ahead of print: 26 October 2011
Published ahead of production: 22 September 2011

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Nicole E. Lopez
Department of Surgery, University of California–San Diego, San Diego, California.
Michael J. Krzyzaniak
Department of Surgery, University of California–San Diego, San Diego, California.
Chelsea Blow
Department of Surgery, University of California–San Diego, San Diego, California.
James Putnam
Department of Surgery, University of California–San Diego, San Diego, California.
Yan Ortiz-Pomales
Department of Surgery, University of California–San Diego, San Diego, California.
Ann-Marie Hageny
Department of Surgery, University of California–San Diego, San Diego, California.
Brian Eliceiri
Department of Surgery, University of California–San Diego, San Diego, California.
Raul Coimbra
Department of Surgery, University of California–San Diego, San Diego, California.
Vishal Bansal
Department of Surgery, University of California–San Diego, San Diego, California.

Notes

Address correspondence to:Vishal Bansal, M.D.University of California San DiegoDepartment of SurgeryDivision of TraumaSurgical Critical Care and Burns200 W. Arbor Drive #8896San Diego, CA 92103E-mail: [email protected]

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No competing financial interests exist.

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