Combined Administration of Poly-ADP-Ribose Polymerase-1 and Caspase-3 Inhibitors Alleviates Neuronal Apoptosis After Spinal Cord Injury in Rats

World Neurosurgery
Wei ZhaoLianshuang Zhang

Abstract

Neuronal apoptosis plays a pivotal role in spinal cord injury (SCI)-induced secondary cellular events. Caspase-dependent and -independent pathways are involved in neuronal apoptosis. Caspase-3 is the final effector of caspase-dependent apoptosis, whereas poly-ADP-ribose polymerase-1 (PARP-1) and apoptosis-inducing factor (AIF) are key executors of caspase-independent apoptosis. However, it remains unclear whether simultaneous inhibition of the 2 apoptosis pathways will be more beneficial for neuronal survival. Therefore, this study investigated the ability of coadministration of the PARP-1 inhibitor 3-aminobenzamide (3-AB) and caspase-3 inhibitor z-DEVD-fmk to attenuate apoptosis in a rat SCI model. The rats were subjected to moderate contusive SCI. Locomotor function was measured using the Basso, Beattie, and Bresnahan rating scales; neuronal apoptosis was detected using transferase-mediated deoxyuridine triphosphate-biotin nick end labeling; and immunohistochemistry and Western blotting were used to measure protein expression. We found the locomotor function of rats was weakened within 7 days post-SCI. At day 7 post-SCI, neuronal apoptosis dramatically increased and the expression of PARP-1, AIF, and cleaved caspase-3 was sig...Continue Reading

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