scholarly journals Targeting Adult Neurogenesis for Poststroke Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianfei Lu ◽  
Anatol Manaenko ◽  
Qin Hu
Keyword(s):  
Stem Cells ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Tissue Repair ◽  
Therapeutic Interventions ◽  
Subgranular Zone ◽  
Brain Repair ◽  
Function Recovery ◽  
Newborn Neurons ◽  
And Function

Adult neurogenesis mainly occurs at the subventricular zone (SVZ) on the walls of the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus (DG). However, the majority of newborn neurons undergo programmed cell death (PCD) during the period of proliferation, migration, and integration. Stroke activates neural stem cells (NSCs) in both SVZ and SGZ. This process is regulated by a wide variety of signaling pathways. However, the newborn neurons derived from adult neurogenesis are insufficient for tissue repair and function recovery. Thus, enhancing the endogenous neurogenesis driven by ischemia and promoting the survival of newborn neurons can be promising therapeutic interventions for stroke. Here, we present an overview of the process of adult neurogenesis and the potential of stroke-induced neurogenesis on brain repair.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Neural stem cells: involvement in adult neurogenesis and CNS repair

2008 ◽  
Vol 363 (1500) ◽  
pp. 2111-2122 ◽  
Author(s):  
Hideyuki Okano ◽  
Kazunobu Sawamoto
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Adult Neurogenesis ◽  
Embryonic Stem ◽  
Adult Brain ◽  
Therapeutic Interventions ◽  
Cell Transplantation Therapy ◽  
Transplantation Therapy

Recent advances in stem cell research, including the selective expansion of neural stem cells (NSCs) in vitro , the induction of particular neural cells from embryonic stem cells in vitro , the identification of NSCs or NSC-like cells in the adult brain and the detection of neurogenesis in the adult brain (adult neurogenesis), have laid the groundwork for the development of novel therapies aimed at inducing regeneration in the damaged central nervous system (CNS). There are two major strategies for inducing regeneration in the damaged CNS: (i) activation of the endogenous regenerative capacity and (ii) cell transplantation therapy. In this review, we summarize the recent findings from our group and others on NSCs, with respect to their role in insult-induced neurogenesis (activation of adult NSCs, proliferation of transit-amplifying cells, migration of neuroblasts and survival and maturation of the newborn neurons), and implications for therapeutic interventions, together with tactics for using cell transplantation therapy to treat the damaged CNS.

scholarly journals Is Forebrain Neurogenesis a Potential Repair Mechanism after Stroke?

2015 ◽  
Vol 35 (7) ◽  
pp. 1220-1221 ◽  
Author(s):  
agos Inta ◽  
Peter Gass
Keyword(s):  
Adult Neurogenesis ◽  
Broad Spectrum ◽  
Subventricular Zone ◽  
Genetic Manipulation ◽  
Gabaergic Interneurons ◽  
Repair Mechanism ◽  
Brain Repair ◽  
Human Neocortex ◽  
Repair Strategy ◽  
Adult Human

The use of adult subventricular zone (SVZ) neurogenesis as brain repair strategy after stroke represents a hot topic in neurologic research. Recent radiocarbon-14 dating has revealed a lack of poststroke neurogenesis in the adult human neocortex; however, adult neurogenesis has been shown to occur, even under physiologic conditions, in the human striatum. Here, these results are contrasted with experimental poststroke neurogenesis in the murine brain. Both in humans and in rodents, the SVZ generates predominantly calretinin (CR)-expressing GABAergic interneurons, which cannot replace the broad spectrum of neuronal subtypes damaged by stroke. Therefore, SVZ neurogenesis may represent a repair mechanism only after genetic manipulation redirecting its differentiation.

scholarly journals Cellular Mechanisms Participating in Brain Repair of Adult Zebrafish and Mammals After Injury

2020 ◽  
Author(s):  
Batoul Ghaddar ◽  
Luisa Lübke ◽  
David COURET ◽  
Sepand Rastegar ◽  
Nicolas Diotel
Keyword(s):  
Stem Cells ◽  
Adult Neurogenesis ◽  
Brain Plasticity ◽  
Adult Zebrafish ◽  
Cellular Mechanisms ◽  
Regenerative Capacity ◽  
Brain Repair ◽  
Cellular Events ◽  
Similarities And Differences ◽  
The Brain

Adult neurogenesis is an evolutionary conserved process occurring in all vertebrates. However, striking differences are observed between the taxa, considering the number of neurogenic niches, the neural stem cell (NSC) identity and brain plasticity under constitutive and injury-induced conditions. Zebrafish has become a popular model for the investigation of the molecular and cellular mechanisms involved in adult neurogenesis. Compared to mammals, the adult zebrafish displays a high number of neurogenic niches distributed throughout the brain. Furthermore, it exhibits a strong regenerative capacity without scar formation or any obvious disabilities. In this review, we will first discuss the similarities and differences regarding (i) the distribution of neurogenic niches in the brain of adult zebrafish and mammals (mainly mouse) and (ii) the nature of the neural stem cells within the main telencephalic niches. In the second part, we will describe the cascade of cellular events occurring after telencephalic injury in zebrafish and mouse. Our study clearly shows that most early events happening right after the brain injury are shared between zebrafish and mouse including cell death, microglia and oligodendrocyte recruitment, as well as injury-induced neurogenesis. In mammals one of the consequences following an injury is the formation of a glial scar that is persistent. This is not the case in zebrafish, which may be one of the main reasons that zebrafish display a higher regenerative capacity.

scholarly journals Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone

2016 ◽  
Author(s):  
Marcos Assis Nascimento ◽  
Lydia Sorokin ◽  
Tatiana Coelho-Sampaio
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Neural Stem Cell ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Stem Cell Niche ◽  
Ependymal Cells ◽  
Cell Niche

AbstractFractones are extracellular matrix structures in the neural stem cell niche of the subventricular zone (SVZ), where they appear as round deposits named bulbs or thin branching lines called stems. Their cellular origin and what determines their localization at this site is poorly studied and it remains unclear whether they influence neural stem and progenitor cells formation, proliferation and/or maintenance. To address these questions, we analyzed whole mount preparations of the lateral ventricle by confocal microscopy using different extracellular matrix and cell markers. We found that bulbs are rarely connected to stems and that they contain laminin α5 and α2 chains, respectively. Fractone bulbs were profusely distributed throughout the SVZ and appeared associated with the center of pinwheels, a critical site for adult neurogenesis. We demonstrate that bulbs appear at the apical membrane of ependymal cells at the end of the first week after birth. The use of transgenic mice lacking laminin α5 gene expression (Lama5) in endothelium and in FoxJ1-expressing ependymal cells, revealed ependymal cells as the source of laminin α5-containing fractone bulbs. Loss of laminin α5 from bulbs correlated with a 60% increase in cell proliferation, as determined by PH3 staining, and with a selective reduction in the number of quiescent neural stem cells in the SVZ. These results indicate that fractones are a key component of the SVZ and suggest that laminin α5 modulates the physiology of the neural stem cell niche.Significance StatementOur work unveils key aspects of fractones, extracellular matrix structures present in the SVZ that still lack a comprehensive characterization. We show that fractones extensively interact with neural stem cells, whereas some of them are located precisely at pinwheel centers, which are hotspots for adult neurogenesis. Our results also demonstrate that fractones increase in size during aging and that their interactions with NSPCs become more complex in old mice. Lastly, we show that fractone bulbs are produced by ependymal cells and that their laminin content regulates neural stem cells.

scholarly journals Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Fabio Cavaliere ◽  
Monica Benito-Muñoz ◽  
Carlos Matute
Keyword(s):  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Neural Regeneration ◽  
Cell Populations ◽  
Subgranular Zone ◽  
Organotypic Cultures ◽  
Cellular Mechanisms ◽  
Cns Disorders ◽  
Pathological Conditions

Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn toin vitromodels. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

scholarly journals Vascular niche contribution to age-associated neural stem cell dysfunction

2017 ◽  
Vol 313 (5) ◽  
pp. H896-H902 ◽  
Author(s):  
Deana M. Apple ◽  
Erzsebet Kokovay
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Dentate Gyrus ◽  
Cell Fate ◽  
Subventricular Zone ◽  
Tissue Homeostasis ◽  
Brain Repair ◽  
Vascular Plexus ◽  
Cell Dysfunction ◽  
Vascular Niche

Neural stem cells (NSCs) persist throughout life in the dentate gyrus and the ventricular-subventricular zone, where they continuously provide new neurons and some glia. These cells are found in specialized niches that regulate quiescence, activation, differentiation, and cell fate choice. A key aspect of the regulatory niche is the vascular plexus, which modulates NSC behavior during tissue homeostasis and regeneration. During aging, NSCs become depleted and dysfunctional, resulting in reduced neurogenesis and poor brain repair. In this review, we discuss the emerging evidence that changes in the vascular niche both structurally and functionally contribute to reduced neurogenesis during aging and how this might contribute to reduced plasticity and repair in the aged brain.

scholarly journals OTX2 signals from the choroid plexus to regulate adult neurogenesis

2018 ◽  
Author(s):  
Anabelle Planques ◽  
Vanessa Oliveira Moreira ◽  
Chantal Dubreuil ◽  
Alain Prochiantz ◽  
Ariel A Di Nardo
Keyword(s):  
Extracellular Matrix ◽  
Cerebrospinal Fluid ◽  
Olfactory Bulb ◽  
Choroid Plexus ◽  
Adult Neurogenesis ◽  
Subventricular Zone ◽  
Supporting Cells ◽  
Multi Level ◽  
Newborn Neurons ◽  
Migratory Stream

AbstractProliferation and migration during adult neurogenesis are regulated by a microenvironment of signaling molecules originating from local vasculature, from cerebrospinal fluid produced by the choroid plexus, and from local supporting cells including astrocytes. Here, we focus on the function of OTX2 homeoprotein transcription factor in the mouse adult ventricular-subventricular zone (V-SVZ) which generates olfactory bulb neurons. We find that OTX2 secreted by choroid plexus is transferred to supporting cells of the V-SVZ and rostral migratory stream. Deletion of Otx2 in choroid plexus affects neuroblast migration and reduces the number of olfactory bulb newborn neurons. Adult neurogenesis was also decreased by expressing secreted single-chain antibodies to sequester OTX2 in the cerebrospinal fluid, demonstrating the importance of non-cell autonomous OTX2. We show that OTX2 activity modifies extracellular matrix components and signaling molecules produced by supporting astrocytes. Thus, we reveal a multi-level and non-cell autonomous role of a homeoprotein and reinforce the choroid plexus and astrocytes as key niche compartments affecting adult neurogenesis.Significance StatementCerebrospinal fluid, local vasculature and non-neurogenic astrocytes are niche compartments that provide a microenvironment for regulating adult mouse neurogenesis. We show that OTX2 homeoprotein secreted by choroid plexus into the cerebrospinal fluid is transferred into non-neurogenic astrocytes of the ventricular-subventricular zone and rostral migratory stream where it regulates extracellular matrix and signaling factors. This non-cell-autonomous activity impacts the number of newborn neurons that integrate the olfactory bulb. Thus, we reveal a multi-level role for OTX2 and reinforce the choroid plexus as a key niche compartment affecting adult neurogenesis.

scholarly journals The microRNA-17 ~ 92 Family as a Key Regulator of Neurogenesis and Potential Regenerative Therapeutics of Neurological Disorders

2020 ◽  
Author(s):  
Xiaohuan Xia ◽  
Yi Wang ◽  
Jialin C. Zheng
Keyword(s):  
Cell Cycle ◽  
Neurological Disorders ◽  
Tissue Repair ◽  
Neuronal Apoptosis ◽  
Recent Progress ◽  
Mirna Family ◽  
Cycle Arrest ◽  
Function Recovery ◽  
Neural Stem Progenitor Cells ◽  
And Function

Abstract miR-17 ~ 92, an miRNA family containing three paralogous polycistronic clusters, was initially considered as an oncogene and was later demonstrated to trigger various physiological and pathological processes. Emerging evidence has implicated miR-17 ~ 92 family as a master regulator of neurogenesis. Through targeting numerous genes that affect cell cycle arrest, stemness deprivation, and lineage commitment, miR-17 ~ 92 family controls the proliferation and neuronal differentiation of neural stem/progenitor cells in both developmental and adult brains. Due to the essential roles of miR-17 ~ 92 family, its misexpression is widely associated with acute and chronic neurological disorders by attenuating neurogenesis and facilitating neuronal apoptosis. The promising neurogenic potential of miR-17 ~ 92 family also makes it a promising “medicine” to activate the endogenous and exogenous regenerative machinery, thus enhance tissue repair and function recovery after brain injury. In this review, we focus on the recent progress made toward understanding the involvement of miR-17 ~ 92 family in regulating both developmental and adult neurogenesis, and discuss the regenerative potential of miR-17 ~ 92 family in treating neurological disorders.

Sign in / Sign up

Export Citation Format

Share Document