Caspase inhibitors rescue spinal motoneurons after root avulsion in neonatal rats

Abstract

The loss of motoneurons following injury (axotomy/avulsion) in neonatal mammals occurs by an apoptotic-like pathway of morphological degeneration. Caspases are important mediators of apoptosis. The present study investigated the effects of the caspase inhibitors, benzyloxycarbonyl-Asp(Ome) fluoromethylketone (Boc-D-FMK), and N-acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-CHO), on the survival of neonatal spinal motoneurons after root avulsion of C7 spinal cord. In control animals, virtually all motoneurons died 7 days after root avulsion. Treatment with either 0.5μg Boc-D-FMK or 1μg Ac-DEVD-CHO enhanced the survival of motoneurons by 80% and 85% of controls, respectively, for up to 7 days post-injury. Lower concentrations resulted in less motoneuron survival. Caspase inhibitors rescue postnatal mammalian motoneurons from injury-induced (avulsion) cell death consistent with the apoptotic nature of their degeneration. (Supported by research grants from the University of Hong Kong and Hong Kong Research Grant Council).