Implantation of Neuronal Stem Cells Enhances Object Recognition without Increasing Neurogenesis after Lateral Fluid Percussion Injury in Mice.

Laura B Ngwenya,Sarmistha Mazumder,Duane J Oswald,Zachary R Porter,Amy Minnema,H Francis Farhadi

doi:10.1155/2018/4209821

Abstract

Cognitive deficits after traumatic brain injury (TBI) are debilitating and contribute to the morbidity and loss of productivity of over 10 million people worldwide. Cell transplantation has been linked to enhanced cognitive function after experimental traumatic brain injury, yet the mechanism of recovery is poorly understood. Since the hippocampus is a critical structure for learning and memory, supports adult neurogenesis, and is particularly vulnerable after TBI, we hypothesized that stem cell transplantation after TBI enhances cognitive recovery by modulation of endogenous hippocampal neurogenesis. We performed lateral fluid percussion injury (LFPI) in adult mice and transplanted embryonic stem cell-derived neural progenitor cells (NPC). Our data confirm an injury-induced cognitive deficit in novel object recognition, a hippocampal-dependent learning task, which is reversed one week after NPC transplantation. While LFPI alone promotes hippocampal neurogenesis, as revealed by doublecortin immunolabeling of immature neurons, subsequent NPC transplantation prevents increased neurogenesis and is not associated with morphological maturation of endogenous injury-induced immature neurons. Thus, NPC transplantation enhances cognitive recovery early after LFPI without a concomitant increase in neuron numbers or maturation.

Highlights

Over 2.8 million Americans experience a traumatic brain injury (TBI), and over 10 million people worldwide are affected [1,2,3,4]
Immunocytochemistry confirmed a predominance of nestin positivity, with some Glial fibrillary acidic protein GFP (GFAP) and Doublecortin days postinjury (DPI) (DCX) immunoreactivity (Figures 2(a)–2(c))
To further confirm the transition from undifferentiated Embryonic stem cells FPI (ES) cells to differentiated neural progenitor cells (NPC), we performed Quantitative Real-Time Polymerase Chain Reactions (qRT-PCR) using RNA extracted from three independent cultures of each cell-type

Summary

Introduction

Over 2.8 million Americans experience a traumatic brain injury (TBI), and over 10 million people worldwide are affected [1,2,3,4]. Patients with cognitive deficits are often unable to return to work and have reduced productivity in society. The more we understand about TBI-induced cognitive deficits, and ways to treat them, the better we can reduce the societal impact of TBI. Animal studies have shown that the transplantation of stem cells shows promise for the recovery of cognitive function after experimental TBI [5,6,7,8]. Studies have shown that priming of the environment, and secretion of growth factors can facilitate graft survival and integration [9,10,11,12], but the mechanism by which stem cell transplantation mediates improvement in cognitive function after experimental TBI is poorly understood

Methods

Results

Discussion

Conclusion