Caspase inhibitors promote the survival of avulsed spinal motoneurons in neonatal rats

Following ventral root avulsion in neonatal animals, the degeneration of sp inal motoneurons occurs by an apoptotic-like morphological pathway. In adul t animals, however, the mechanism of degeneration of injured motoneurons is still controversial. Because caspases are important mediators of apoptosis , we have investigated the effects of the caspase inhibitors, benzyloxycarb onyl-Asp(OMe)fluoromethylketone (Boc-D-FMK), and Nacetyl-Asp-Glu-Val-Asp al dehyde (Ac-DEVD-CHO) on the survival of neonatal and adult spinal motoneuro ns after root avulsion of the C7 spinal cord. In the control neonatal anima ls, virtually all motoneurons had degenerated by 7 days following root avul sion. Treatment with either 0.5 mug Boc-D-FMK or 1 mug Ac-DEVD-CHO enhanced the survival of motoneurons to 80% and 85% for up to 2 weeks post-injury. By 21 days post-injury, 70% of avulsed motoneurons were still present after Boc-D-FMK treatment, whereas all avulsed motoneurons died after treatment with Ac-DEVD-CHO. In adult animals, neither inhibitor was neuroprotective f or motoneurons following root avulsion. in summary, the inhibition of caspa ses effectively rescued avulsed neonatal motoneurons which are died by apop totic pathway. By contrast, because caspase inhibitors failed to rescue inj ured motoneurons in adult animals, their death may occur by a non-apoptotic pathway. NeuroReport 12:541-545 (C) 2001 Lippincott Williams & Wilkins.