Tohoku J. Exp. Med., 2005, 207(2)

Beneficial Effect of Methylprednisolone on Cardiac Myocytes in a Rat Model of Severe Brain Injury

MUSTAFA EMIR, KANAT OZISIK,¹ KERIM CAGLI, PINAR OZISIK,² SERDAR TUNCER,³ VEDAT BAKUY, ERKAN YILDIRIM,¹ KAMER KILINC⁴ and KAMIL GOL

Department of Cardiovascular Surgery, TYIH, Ankara, and ¹Department of Cardiovascular Surgery, Numune Education and Research Hospital, Ankara, ²Institute of Neurological Sciences and Psychiatry, ⁴Department of Biochemistry, Hacettepe University Medical Faculty, Ankara, and ³Metis Biotechnology Ltd., Ankara, Turkey

Cardiac injury, occurred after traumatic brain injury (TBI), has been recognized for more than a century. Bcl-2 is a key regulatory component of the mitochondrial cell death pathway, and its overexpression is cytoprotective in many cell types. The therapeutic agents, which induce the expression of bcl-2 protein, might provide a new therapy to prevent cardiac myocyte damage following TBI. In this study, we investigated whether methylprednisolone sodium succinate (MPSS) influences the expression of bcl-2 in the heart. Wistar-Albino female rats underwent TBI (300 g/cm) generated by the weight-drop method, and were left untreated (n = 6) or treated with either MPSS (30 mg/kg) (n = 6) or vehicle (albumin solution) (n = 6). The heart was isolated from each animal with TBI. For comparison, the hearts were isolated from sham-operated (n = 6) and control rats (n = 6). The relative expression of bcl-2 mRNA in the heart was quantitated by real-time polymerase chain reaction. We also assessed lipid peroxidation in the heart tissue by determining the concentration of thiobarbituric acid-reactive substances (TBARs) as an indicator of tissue damage. The bcl-2 expression level was significantly higher in the hearts of MPSS-treated rats compared to that of other TBI groups (p < 0.0001). Moreover, TBI increased the lipid peroxidation in the heart, which was significantly reduced by the treatment with MPSS (p < 0.0001). These findings provide evidence for the efficacy of MPSS in protection of cardiac myocytes to achieve optimal heart donation after TBI in heart transplantation.

keywords ——methylprednisolone; bcl-2; apoptosis; TBARs; myocytes; head injuries

© 2005 Tohoku University Medical Press

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Corresponding: Kanat Ozisik, M.D., 23.cad Kirkkonaklar mah. Simkent Sitesi 2.blok No:6/13, 06610 Ankara, Turkey.

e-mail: sozisik2002@yahoo.com