Rosiglitazone, a PPAR gamma agonist, attenuates inflammation after surgical brain injury in rodents.
BACKGROUND
Surgical brain injury (SBI) is unavoidable during many neurosurgical procedures. This inevitable brain injury can result in post-operative complications including brain edema, blood-brain barrier disruption (BBB) and cell death in susceptible areas. Rosiglitazone (RSG), a PPAR-gamma agonist, has been shown to reduce inflammation and provide neuroprotection in experimental models of ischemia and intracerebral hemorrhage. This study was designed to evaluate the neuroprotective effects of RSG in a rodent model of SBI.


METHODS
65 adult male Sprague-Dawley rats were randomly divided into sham, vehicle and treatment groups. RSG was administered intraperitoneally in two dosages (1 mg/kg/dose, 6 mg/kg/dose) 30 min before surgery, and 30 min and 4 h after surgery. Animals were euthanized 24 h following neurological evaluation to assess brain edema and BBB permeability by IgG staining. Inflammation was examined using myeloperoxidase (MPO) assay and double-labeling fluorescent immunohistochemical analysis of IL-1beta and TNF-alpha.


RESULTS
Localized brain edema was observed in tissue surrounding the surgical injury. This brain edema was significantly higher in rats subjected to SBI than sham animals. Increased IgG staining was present in affected brain tissue; however, RSG reduced neither IgG staining nor brain edema. RSG also did not improve neurological status observed after SBI. RSG, however, significantly attenuated MPO activity and qualitatively decreased IL-1beta and TNF-alpha expression compared to vehicle-treated group.


CONCLUSIONS
SBI causes increased brain edema, BBB disruption and inflammation localized along the periphery of the site of surgical resection. RSG attenuated inflammatory changes, however, did not improve brain edema, BBB disruption and neurological outcomes after SBI.
Hyong
Amy
A
Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Jadhav
Vikram
V
Lee
Steve
S
Tong
Wenni
W
Rowe
Jamaine
J
Zhang
John H
JH
Tang
Jiping
J
D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D001930:Brain Injuries / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007431:Intraoperative Complications; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019635:Neurosurgical Procedures / Q000009:adverse effects; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009195:Peroxidase