Antiapoptotic and Anti-Inflammatory Effects of CPCGI in Rats with Traumatic Brain Injury

Abstract

Background: Compound porcine cerebroside and ganglioside injection (CPCGI) has been used for the treatment of certain brain disorders. Apoptosis and inflammation were reported to be involved in the pathogenesis of traumatic brain injury (TBI). Therefore, this study primarily investigated the effects of CPCGI on mitochondrial apoptotic signaling and PARP/ NF-kappa B inflammatory signaling in a rat model of controlled cortical impact (CCI). Materials and Methods: CPCGI (0.6 mL/kg) was administered intraperitoneally 30 min after the induction of CCI. Mitochondrial apoptotic signaling and PARP/NF-kappa B inflammatory signaling were evaluated 24 h after CCI, and apoptotic cell death, neutrophil infiltration, and astrocyte and microglial activation were determined by TUNEL and immunofluorescent staining 3 days after CCI. Results: 1) CPCGI markedly enhanced cytosolic and mitochondrial Bcl-xL levels, the mitochondrial Bcl-xL/Bax ratio, and mitochondrial cytochrome (cyt) c levels and reduced cytosolic cyt c levels, caspase-3 activity, and nuclear AIF levels in brain tissues after traumatic injury; however, CPCGI had no significant effects on cytosolic or mitochondrial Bax levels, the cytosolic Bcl-xL/Bax ratio, or mitochondrial AIF levels. Moreover, CPCGI markedly reduced the TUNEL staining score in the contusion region. 2) CPCGI markedly reduced cytosolic and nuclear PARP levels and nuclear NF-kappa B p65 levels in brain tissues after traumatic injury but had no significant effect on cytosolic NF-kappa B p65 levels. In addition, CPCGI markedly reduced caspase-1 activity and the levels of caspase-1, ICAM1, TNF-alpha, and IL-1 beta in brain tissues after traumatic injury and decreased the immunoreactivities of neutrophils, GFAP and Iba-1 in the region of CCI-induced contusion. Conclusion: These data suggest that CPCGI can reduce brain injury due to trauma by suppressing both mitochondrial apoptotic signaling and PARP/NF-kappa B inflammatory signaling.