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.

Neuronal differentiation of human mesenchymal stem cells: Changes in the expression of the Alzheimer's disease-related gene seladin-1

“…As a further clue supporting the hypothesis that seladin-1 is a predominant product of stem cells, we also detected a high amount of seladin-1 mRNA in the human adult hippocampus and spinal cord, which have been shown to contain neural stem cells with neurogenic activity [8][9][10] (Table 1). The level of seladin-1 mRNA in these regions was rather close to the amount of transcript detected in the adrenal cortex, one of the tissues in which the highest levels of transcription had been detected [1].…”

“…With regard to this point, it is worth mentioning that, according to the findings of Greeve et al [1], we detected high levels of seladin-1 transcript in the adult hippocampus, a well-known neurogenic brain region [8], and which is one of the areas affected in AD. Similarly, a high amount of seladin-1 mRNA was found in the spinal cord, in which stem cells with neurogenic properties have been recently described [9,10]. Alternatively, our findings might indicate a modification of the neurogenic properties of the adult brain as a consequence of neuronal damage and therefore of AD itself.…”

“…In fact, although neural stem cells are present in many other areas of the adult brain, they do not appear to maintain the ability to differentiate into neurons [8]. Very recently, stem cells with neurogenic activity have been described also in the adult spinal cord [9,10], which classically was not considered a neurogenic region [11]. Noteworthy, Greeve et al [1] detected the presence of rather high levels of expression of seladin-1 both in human normal hippocampus and spinal cord [1].…”

Getting the right stuff: Controlling neural stem cell state and fate in vivo and in vitro with biomaterials

“…Tracing of nestin positive neural progenitors resident in the adult spinal cord has revealed that these cells proliferate and differentiate into neurons at the lesion area following dorsal compression injury [19]. Focal ischemia was shown to increase the normal rate of neurogenesis in the cortex and hippocampus [20,21], and the results could be enhanced by exogenous delivery of growth factors [21].…”

Cells of adult brain germinal zone have properties akin to hair cells and can be used to replace inner ear sensory cells after damage

“…Ependymal cells adjacent to the spinal canal proliferate extensively upon spinal cord injuries (16,17). Proliferation of adult brain LV ependymal cells (18) can also be detected after a stroke.…”