Early Response of Endogenous Adult Neural Progenitor Cells to Acute Spinal Cord Injury in Mice

Abstract Adult neural progenitor cells (NPCs) are an attractive source for functional replacement in neurodegenerative diseases and traumatic injury to the central nervous system (CNS). It has been shown that transplantation of neural stem cells or NPCs into the lesioned region partially restores CNS function. However, the capacity of endogenous NPCs in replacement of neuronal cell loss and functional recovery of spinal cord injury (SCI) is apparently poor. Furthermore, the temporal and spatial response of endogenous adult NPCs to SCI remains largely undefined. To this end, we have analyzed the early organization, distribution, and potential function of NPCs in response to SCI, using nestin enhancer (promoter) controlled LacZ reporter transgenic mice. We showed that there was an increase of NPC proliferation, migration, and neurogenesis in adult spinal cord after traumatic compression SCI. The proliferation of NPCs detected by 5-bromodeoxyuridine incorporation and LacZ staining was restricted to the ependymal zone (EZ) of the central canal. During acute SCI, NPCs in the EZ of the central canal migrated vigorously toward the dorsal direction, where the compression lesion is generated. The optimal NPC migration occurred in the adjacent region close to the epicenter. More significantly, there was an increased de novo neurogenesis from NPCs 24 hours after SCI. The enhanced proliferation, migration, and neurogenesis of (from) endogenous NPCs in the adult spinal cord in response to SCI suggest a potential role for NPCs in attempting to restore SCI-mediated neuronal dysfunction.