Surgically induced brain injury in rats: the effect of erythropoietin.
Brain tissue at the edge of a surgical resection site is at risk for damage from direct trauma, retractor stretch, hemorrhage, edema, and electrocautery. In this study we used a new rodent model of surgically induced brain injury (SBI) to study this tissue at the edge of a resection site. The SBI model entails stereotaxic resection of part of the right frontal lobe. We tested pretreatment with erythropoietin, a known neuroprotectant, for protective effects in this model. Three groups of male Sprague-Dawley rats (280-330g) were used: SBI without treatment (n=63), SBI with EPO treatment (n=76), and Sham surgery (n=12). Rats were sacrificed 24h, 72h, and 7 days after SBI or Sham surgery. Postoperative assessment included mortality, histology, immunohistochemistry, Evans blue exudation, brain water content, and magnetic resonance imaging. No difference was found between untreated and EPO-treated groups in mortality, histology, TUNEL, magnetic resonance imaging, or blood-brain-barrier breakdown. The EPO-treated group had statistically more brain water content at 24h than the untreated group. Immunohistochemistry demonstrated a qualitative increase in VEGF in the EPO-treatment group. We conclude that EPO does not ameliorate damage in SBI, and may increase brain edema early after surgery.
Matchett
Gerald
G
Department of Anesthesiology, Loma Linda University, School of Medicine, Loma Linda, CA, United States.
Hahn
Joseph
J
Obenaus
Andre
A
Zhang
John
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001834:Body Water / Q000737:chemistry; D001923:Brain Chemistry; D001930:Brain Injuries / Q000401:mortality / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D004396:Coloring Agents; D004921:Erythropoietin / Q000494:pharmacology*; D005070:Evans Blue; D005455:Fluorescent Antibody Technique; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents; D019635:Neurosurgical Procedures; D051381:Rats; D017207:Rats, Sprague-Dawley; D017467:Receptors, Erythropoietin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D004396:Coloring Agents; D007074:Immunoglobulin G; D018696:Neuroprotective Agents; D017467:Receptors, Erythropoietin; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D005070:Evans Blue; D053148:Caspase 3