Neural precursor cells in the ischemic brain – integration, cellular crosstalk, and consequences for stroke recovery

Abstract

After an ischemic stroke, neural precursor cells (NPCs) proliferate within major germinal niches of the brain. Endogenous NPCs subsequently migrate toward the ischemic lesion where they promote tissue remodeling and neural repair. Unfortunately, this restorative process is generally insufficient and thus unable to support a full recovery of lost neurological functions. Supported by solid experimental and preclinical data, the transplantation of exogenous NPCs has emerged as a potential tool for stroke treatment. Transplanted NPCs are thought to act mainly via trophic and immune modulatory effects, thereby complementing the restorative responses initially executed by the endogenous NPC population. Recent studies have attempted to elucidate how the therapeutic properties of transplanted NPCs vary depending on the route of transplantation. Systemic NPC delivery leads to potent immune modulatory actions, which prevent secondary neuronal degeneration, reduces glial scar formation, diminishes oxidative stress and stabilizes blood–brain barrier integrity. On the contrary, local stem cell delivery allows for the accumulation of large numbers of transplanted NPCs in the brain, thus achieving high levels of locally available tissue trophic factors, which may better induce a strong endogenous NPC proliferative response. Herein we describe the diverse capabilities of exogenous (systemically vs. locally transplanted) NPCs in enhancing the endogenous neurogenic response after stroke, and how the route of transplantation may affect migration, survival, bystander effects and integration of the cellular graft. It is the authors’ claim that understanding these aspects will be of pivotal importance in discerning how transplanted NPCs exert their therapeutic effects in stroke.

NSI‐189, a small molecule with neurogenic properties, exerts behavioral, and neurostructural benefits in stroke rats

“…That the brain remodels itself after stroke has been documented (Hermann et al, 2014; Tajiri et al, 2012; Watson et al, 2015; Zhang & Chopp, 2015), but this host repair mechanism is not sufficient to account for sustained relevant stroke recovery (Doeppner et al, 2009; Hess & Borlongan, 2008a; Hu et al, 2013; Kuge et al, 2009). Exogenous treatment, either pharmacologically or via stem cell transplantation, designed to enhance host brain regenerative process is needed to achieve clinically relevant functional outcomes in stroke (Kaneko et al, 2012; Matsukawa et al, 2009; Peña & Borlongan, 2015; Tajiri et al, 2012; Wang et al, 2014; Yasuhara et al, 2010).…”

Applications of the Keap1–Nrf2 system for gene and cell therapy

“…Similarly to chronic neurological disorders, stem cell transplantation represents an attractive treatment strategy for promotion of repair after acute ischemic stroke (reviewed in [156][157][158][159] ) or traumatic CNS injuries (reviewed in [91,[160][161][162] …”

Sonic Hedgehog Signaling Mediates Resveratrol to Increase Proliferation of Neural Stem Cells After Oxygen-Glucose Deprivation/Reoxygenation Injury in Vitro

“…Furthermore, the transplantation of exogenous NSCs is restricted because sources are limited, immunological rejection can occur, and there are ethical considerations. Therefore, there is great interest in the identification of drugs and rehabilitation methods for activating, enhancing, and regulating the regeneration, migration, differentiation, and integration for endogenous NSCs [3,4]. …”