Effect of erythropoietin on brain tissue after experimental head trauma in rats

• Published in: Surgical neurology Vol. 68; no. 5; pp. 547 - 555
• Main Authors: Akdemir Ozisik, Pinar, MD, Oruckaptan, Hakan, MD, PhD, Ozdemir Geyik, Pinar, PhD, Misirlioglu, Muge, PhD, Sargon, Mustafa F., MD, PhD, Kılınc, Kamer, MD, Ozgen, Tuncalp, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2007
• Subjects: Animals; Apoptosis; bcl-2; Brain - drug effects; Brain - metabolism; Brain - ultrastructure; Brain Injuries - drug therapy; Brain Injuries - metabolism; Brain Injuries - pathology; Brain injury; Electron microscopy; Erythropoietin; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Free Radicals - metabolism; Lipid peroxidation; Lipid Peroxidation - drug effects; Methylprednisolone; Microscopy, Electron, Transmission; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Neurology; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Wistar; Recombinant Proteins; RNA, Messenger - metabolism; Surgery; Survivin; histologic injury score; EPO; corticosteriod randomization after significant head injury; CNS; LPO; mRNA; TBARs; MDA; Methylprednisolone; complementary DNA; CRASH; TAMRA; analysis of variance; messenger RNA; ANOVA; RT-PCR; reverse transcriptase polymerase chain reaction; 6-carboxyfluorescein; cDNA; TBI; malondialdehyde; transmission electron microscopy; erythropoietin; bcl-2; methylprednisolone sodium succinate; MPSS; thiobarbituric acid reactive substances; traumatic brain injury; AMV; Survivin; Electron microscopy; lipid peroxidation; central nervous system; inhibitor of apoptosis protein; FAM; HIS; intracranial pressure; avian myeloblastosis virus; 6-carboxytetramethylrhodamine; ICP; IAP; TEM; Brain injury; Apoptosis; Erythropoietin; Lipid peroxidation
• ISSN: 0090-3019; 1879-3339
• DOI: 10.1016/j.surneu.2007.01.030

Abstract Background The purpose of this study was to investigate the effect of EPO on LPO, on ultrastructural findings, and on antiapoptotic bcl-2 and survivin gene expressions after TBI. The authors also compared the activity of EPO with that of MPSS. Methods Wistar rats were divided into 6 groups: sham-operated, control, moderate TBI-alone (300 g/cm), TBI + EPO-treated (1000 IU/kg), TBI + MPSS-treated (30 mg/kg), and TBI + vehicle-treated (0.4 mL albumin solution) groups. Results Compared with the levels in control and sham-operated animals, LPO was significantly elevated in rats in the trauma-alone group. The administration of EPO and MPSS significantly decreased the LPO levels ( P < .05). Trauma also increases the antiapoptotic bcl-2 gene expression significantly at 24 hours postinjury ( P < .05), but it has no effect on survivin expression. The EPO and MPSS treatments caused significant elevation in both gene expressions ( P < .05). It is also showed that MPSS has more protective effect than EPO on brain ultrastructure, especially on the structure of small- ( P < .05) and medium-sized myelinated axons, after TBI. Conclusions EPO has protective effects after moderate TBI, and this effect seems better than MPSS on antiapoptotic gene expression and LPO. The protection of cerebral subcellular organelles after traumatic injury is more prominent in MPSS-treated animals than EPO-treated animals quantitatively. This experimental study indicates that the benefits of EPO in the management of TBI have promising results and prompts further studies on the difference between EPO and MPSS in histopathological findings at the subcellular level.