Our laboratory focuses on studying mechanisms underlying spinal cord injury (SCI) and developing novel repair strategies to improve anatomical reorganization and functional recovery in experimental models of SCI.Currently,two lines of research are being conducted.The first one is on neuroprotection.Specifically,we are investigating whether phospholipase A2 (PLA2),a diverse family of phospholipid enzymes,plays a critical role in the pathogenesis of SCI.After SCI,both PLA2 activity and cytosolic PLA2 (cPLA2) expression increased significantly and the cPLA2 expression was localized mainly in neurons and oligodendrocytes.Both PLA2 and melittin,an activator of endogenous PLA2,induced spinal neuronal death in vitro which was substantially reversed by mepacrine,a PLA2 inhibitor.When PLA2 or melittin was microinjected into the normal cord,the former induced confined demyelination and latter diffuse tissue necrosis.Both injections induced inflammation,oxidation and tissue damage,resulting in corresponding electrophysiological and behavioral impairments.Remarkably,the PLA2-induced demyelination was substantially reversed by mepacrine.Thus,this study has identified PLA2 as a key molecule that increases substantially after SCI and induces neuronal death and oligodendrocyte demyelination.The multiple sites of PLA2 action indicate that it may serve as a central molecule in mediating secondary SCI.A second line of research is to use cellular transplantation strategies to promote axonal regeneration through and beyond a lesion gap after SCI.SCI incurs disconnection of axons.A successful repair strategy requires reconnection of these damaged axons to their appropriate targets.Here we report the construction of a continuous growth-promoting pathway,formed by grafted SCs overexpressing glial cell line-derived neurotrophic factor.We demonstrate that such a growth-promoting pathway,extending from the axonal cut ends to the site of innervation in the distal host spinal cord,promoted regeneration of central nervous system axons,particularly those originated from descending propriospinal neurons (DPSNs),through and beyond the lesion gap of a spinal cord lateral hemisection.Within the distal host spinal cord,regenerated DPSN axons formed synapses with host neurons leading to the restoration of action potentials and partial recovery of function.It is our belief that the final repair of the injured spinal cord may be achievable by combining an early phase of neuroprotection and later phase of transplantation-mediated axonal regeneration.