Amy Hyong

Abstract

Introduction: Brain injury can be caused by neurosurgical procedures themselves, due to direct trauma, retractor stretch, intraoperative hemorrhage and electrocautery damage. As a result of this surgical brain injury (SBI) postoperative complications such as inflammation, brain edema, and cell death can occur in the susceptible brain areas. Cerebral inflammation is a known contributor to the pathophysiology of brain injury. Following brain injury, the release of inflammatory mediators facilitates the development of BBB breakdown, cerebral edema, oxidative stress and neuronal death, resulting in further tissue damage in the brain and poor neurological outcomes. This study evaluates whether the use of a PPAR-γ agonist RSG can reduce postoperative complications and provide neuroprotection in a rodent model of SBI.

Methods: SBI rat model incorporates partial resection of frontal lobe with reproducible blood brain barrier (BBB) disruption, brain edema, and neuronal death in the susceptible brain tissue. RSG was administered intraperitoneally in two treatment regimens: 1mg/kg/dose and 6mg/kg/dose. Animals were tested for neurological and sensorimotor deficits and euthanized at 24 hours post surgery to measure brain water content, neutrophil infiltration as an indication of inflammation (MPO), and BBB disruption through IgG staining.

Results: Brain edema was significantly higher in vehicle-treated rats when compared to sham rats. Treatment with both dosages of RSG did not attenuate brain edema. Increased IgG staining was qualitatively illustrated surrounding the site of surgical resection although no apparent reduction in IgG staining was observed in treated rats. RSG, however, significantly reversed the MPO activity, which was increased after surgery in vehicle-treated rats. There were no significant differences in neurological scores between groups.

Conclusion: Treatment with Rosiglitazone attenuated inflammation; however, did not reduce brain edema, improve BBB integrity or neurological outcomes after SBI. This may be attributed to a variety of causes including the fact that RSG may target different mechanisms in SBI as well as the early time course chosen for this study. Future studies will be directed towards understanding the mechanism and timing of inflammation in the SBI model that will enable potential neuroprotective agents to be administered at time points to produce the most beneficial effects.

LLU Discipline

Physiology

Department

Physiology

School

Graduate Studies

First Advisor

Jiping Tang

Second Advisor

Andre Obenaus

Third Advisor

John H. Zhang

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

2008

Date (Title Page)

9-2008

Language

English

Library of Congress/MESH Subject Headings

Brain Injuries -- physiopathology; Neurosurgery; PPAR Gamma -- drug effects; Body Water -- physiology; Brain Injuries -- etiology; Brain Edema; Blood Brain Barrier; Rodents; Peroxisome Proliferators; Anti-Inflammatory Agents; Immunohistochemistry -- methods.

Type

Thesis

Page Count

xi; 44

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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