Hyperbaric Oxygenation Prevents Loss of Immature Neurons in the Adult Hippocampal Dentate Gyrus Following Brain Injury.

A growing body of evidence suggests that hyperbaric oxygenation (HBO) may affect the activity of adult neural stem cells (NSCs). Since the role of NSCs in recovery from brain injury is still unclear, the purpose of this study was to investigate the effects of sensorimotor cortex ablation (SCA) and HBO treatment (HBOT) on the processes of neurogenesis in the adult dentate gyrus (DG), a region of the hippocampus that is the site of adult neurogenesis. Ten-week-old Wistar rats were divided into groups: Control (C, intact animals), Sham control (S, animals that underwent the surgical procedure without opening the skull), SCA (animals in whom the right sensorimotor cortex was removed via suction ablation), and SCA + HBO (operated animals that passed HBOT). HBOT protocol: pressure applied at 2.5 absolute atmospheres for 60 min, once daily for 10 days. Using immunohistochemistry and double immunofluorescence labeling, we show that SCA causes significant loss of neurons in the DG. Newborn neurons in the subgranular zone (SGZ), inner-third, and partially mid-third of the granule cell layer are predominantly affected by SCA. HBOT decreases the SCA-caused loss of immature neurons, prevents reduction of dendritic arborization, and increases proliferation of progenitor cells. Our results suggest a protective effect of HBO by reducing the vulnerability of immature neurons in the adult DG to SCA injury.

Electroacupuncture Promotes the Survival of the Grafted Human MGE Neural Progenitors in Rats with Cerebral Ischemia by Promoting Angiogenesis and Inhibiting Inflammation.

Stem cells have the potential as a regenerative therapy for cerebral ischemia by improving functional outcomes. However, cell transplantation has some limitations, including a low rate of the grafted cell survival. There is still a major challenge of promoting the harmonious symbiosis between grafted cells and the host. Acupuncture can effectively improve the functional outcome after cerebral ischemia. The present study evaluated the therapeutic effects and explored the mechanism of combined medial ganglionic eminence (MGE) neural progenitors differentiated from human embryonic stem cells (hESCs) with electroacupuncture (EA) in a bilateral common carotid artery occlusion (2VO) rat model. The results showed that EA could promote the survival of the grafted MGE neural progenitors differentiated from hESCs and alleviate learning and memory impairment in rats with cerebral ischemia. This may have partially resulted from inhibited expression of TNF-α and IL-1ß and increased vascular endothelial growth factor (VEGF) expression and blood vessel density in the hippocampus. Our findings indicated that EA could promote the survival of the grafted MGE neural progenitors and enhance transplantation therapy's efficacy by promoting angiogenesis and inhibiting inflammation.

Promotive effects of tetrahydroxystilbene glucoside on the differentiation of neural stem cells from the mesencephalon into dopaminergic neurons.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the loss of midbrain dopaminergic (DA) neurons. Neural stem cells (NSCs) are the most promising cells for cell-replacement therapy for PD. However, the poor differentiation and maturation of DA neurons and decreased cell survival after transplantation are a challenge. Tetrahydroxystilbene glucoside (2,3,5,4'-tetrahydroxystilbene-2-O-glucoside; TSG), an active component of the popular traditional Chinese medicinal plant Polygonum multiflorum Thunb, possesses multiple pharmacological actions. In this study, we determined whether TSG can induce neural stem cell (NSCs) differentiation into neurons, especially DA neurons, and the possible involvement of Wnt/ß-catenin signaling pathways. Results revealed that NSCs differentiated primarily into astrocytes when cultured in 2 % serum-containing medium. However, TSG treatment during NSC differentiation in vitro increased the number of Tuj-1-positive neurons, as well as the proportion of tyrosine hydroxylase(TH)-positive cells and dopamine- transporter- positive neurons, a late marker of mature DA neurons. We also found that TSG enhanced the expression of nuclear receptor related factor 1, a transcription factor specific for the development and maintenance of midbrain DA neurons in inducing NSC differentiation into TH -immunoreactive DA neurons. Moreover, TSG upregulated the expression of Wnt/ß-catenin signaling molecules (Wnt1, Wnt3a, Wnt5a, and ß-catenin). However, these promoting effects were significantly inhibited by the application of IWR1, a Wnt signaling-specific blocker in culture. Our findings suggested that TSG may have potential in inducing the DA neuronal differentiation of mouse NSCs mediated by triggering the Wnt/ß-catenin signaling pathway. These results indicated the possible role for TSG in the transplantation of NSCs for PD.

Putative adult neurogenesis in palaeognathous birds: The common ostrich (Struthio camelus) and emu (Dromaius novaehollandiae).

In the current study, we examined adult neurogenesis throughout the brain of the common ostrich (Struthio camelus) and emu (Dromaius novaehollandiae) using immunohistochemistry for the endogenous markers PCNA which labels proliferating cells, and DCX, which stains immature and migrating neurons. The distribution of PCNA and DCX labelled cells was widespread throughout the brain of both species. The highest density of cells immunoreactive to both markers was observed in the olfactory bulbs and the telencephalon, especially the subventricular zone of the lateral ventricle. Proliferative hot spots, identified with strong PCNA and DCX immunolabelling, were identified in the dorsal and ventral poles of the rostral aspects of the lateral ventricles. The density of PCNA immunoreactive cells was less in the telencephalon of the emu compared to the common ostrich. Substantial numbers of PCNA immunoreactive cells were observed in the diencephalon and brainstem, but DCX immunoreactivity was weaker in these regions, preferentially staining axons and dendrites over cell bodies, except in the medial regions of the hypothalamus where distinct DCX immunoreactive cells and fibres were observed. PCNA and DCX immunoreactive cells were readily observed in moderate density in the cortical layers of the cerebellum of both species. The distribution of putative proliferating cells and immature neurons in the brain of the common ostrich and the emu is widespread, far more so than in mammals, and compares with the neognathous birds, and suggests that brain plasticity and neuronal turnover is an important aspect of cognitive brain functions in these birds.

Vitamin D deficiency as a potential risk factor for accelerated aging, impaired hippocampal neurogenesis and cognitive decline: a role for Wnt/ß-catenin signaling.

Vitamin D is an essential fat-soluble vitamin that participates in several homeostatic functions in mammalian organisms. Lower levels of vitamin D are produced in the older population, vitamin D deficiency being an accelerating factor for the progression of the aging process. In this review, we focus on the effect that vitamin D exerts in the aged brain paying special attention to the neurogenic process. Neurogenesis occurs in the adult brain in neurogenic regions, such as the dentate gyrus of the hippocampus (DG). This region generates new neurons that participate in cognitive tasks. The neurogenic rate in the DG is reduced in the aged brain because of a reduction in the number of neural stem cells (NSC). Homeostatic mechanisms controlled by the Wnt signaling pathway protect this pool of NSC from being depleted. We discuss in here the crosstalk between Wnt signaling and vitamin D, and hypothesize that hypovitaminosis might cause failure in the control of the neurogenic homeostatic mechanisms in the old brain leading to cognitive impairment. Understanding the relationship between vitamin D, neurogenesis and cognitive performance in the aged brain may facilitate prevention of cognitive decline and it can open a door into new therapeutic fields by perspectives in the elderly.

Complete neural stem cell (NSC) neuronal differentiation requires a branched chain amino acids-induced persistent metabolic shift towards energy metabolism.

Neural stem cell (NSC) neuronal differentiation requires a metabolic shift towards oxidative phosphorylation. We now show that a branched-chain amino acids-driven, persistent metabolic shift toward energy metabolism is required for full neuronal maturation. We increased energy metabolism of differentiating neurons derived both from murine NSCs and human induced pluripotent stem cells (iPSCs) by supplementing the cell culture medium with a mixture composed of branched-chain amino acids, essential amino acids, TCA cycle precursors and co-factors. We found that treated differentiating neuronal cells with enhanced energy metabolism increased: i) total dendritic length; ii) the mean number of branches and iii) the number and maturation of the dendritic spines. Furthermore, neuronal spines in treated neurons appeared more stable with stubby and mushroom phenotype and with increased expression of molecules involved in synapse formation. Treated neurons modified their mitochondrial dynamics increasing the mitochondrial fusion and, consistently with the increase of cellular ATP content, they activated cellular mTORC1 dependent p70S6 K1 anabolism. Global transcriptomic analysis further revealed that treated neurons induce Nrf2 mediated gene expression. This was correlated with a functional increase in the Reactive Oxygen Species (ROS) scavenging mechanisms. In conclusion, persistent branched-chain amino acids-driven metabolic shift toward energy metabolism enhanced neuronal differentiation and antioxidant defences. These findings offer new opportunities to pharmacologically modulate NSC neuronal differentiation and to develop effective strategies for treating neurodegenerative diseases.

Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation.

INTRODUCTION: Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination. MATERIAL AND METHODS: We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site. RESULTS: Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms. CONCLUSION: Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.

Insulin-like growth factor-1 enhances neuroprotective effects of neural stem cell exosomes after spinal cord injury via an miR-219a-2-3p/YY1 mechanism.

Spinal cord injury (SCI) remains the most common cause of paralysis, and there are no effective therapies for SCI patients. Neural stem cell (NSC)-derived exosomes can attenuate apoptosis and neuroinflammation after traumatic spinal cord injury, but the mechanisms underlying these effects remain unclear. Here, we examined the efficacy of miRNAs isolated from exosomes as treatments for SCI and characterized their mechanisms of action. Furthermore, we evaluated the effects of exosomes formed in the presence of insulin growth factor-1 (IFG-1, IGF-Exo), which promotes neural proliferation and regeneration, as well as normal exosomes (Nor-Exo) and compared control and H2O2-treated groups both invitro and invivo. Using microRNA sequencing and qRT-PCR, we identified miR-219a-2-3p, levels of which were higher in the IGF-Exo than Nor-Exo group and played crucial anti-inflammatory and anti-apoptosis roles. Additional experiments revealed that IGF-Exo inhibits YY1 expression through up-regulation of miR-219a-2-3p. This in turn inhibits the NF-κB pathway, partly inhibiting neuroinflammation and promoting the neuroprotective effects after SCI.

Neural responses to electrical stimulation in 2D and 3D in vitro environments.

Electrical stimulation (ES) to manipulate the central (CNS) and peripheral nervous system (PNS) has been explored for decades, recently gaining momentum as bioelectronic medicine advances. The application of ES in vitro to modulate a variety of cellular functions, including regenerative potential, migration, and stem cell fate, are being explored to aid neural degeneration, dysfunction, and injury. This review describes the materials and approaches for the application of ES to the PNS and CNS microenvironments, towards an improved understanding of how ES can be harnessed for beneficial clinical applications. Emphasized are some recent advances in ES, including conductive polymers, methods of charge transfer, impact on neural cells, and a brief overview of alternative methodologies for cellular targeting including magneto, ultrasonic, and optogenetic stimulation. This review will examine how heterogenous cell populations, including neurons, glia, and neural stem cells respond to a wide range of conductive 2D and 3D substrates, stimulation regimes, known mechanisms of response, and how cellular sources impact the response to ES.

The role of glutamine in neurogenesis promoted by the green tea amino acid theanine in neural progenitor cells for brain health.

The green tea amino acid theanine is abundant in green tea rather than black and oolong teas, which are all made of the identical tea plant "Chanoki" (Camellia sinensis). Theanine has a molecular structure close to glutamine (GLN) compared to glutamic acid (Glu), in terms of the absence of a free carboxylic acid moiety from the gamma carbon position. Theanine efficiently inhibits [3H]GLN uptake without affecting [3H]Glu uptake in rat brain synaptosomes. In contrast to GLN, however, theanine markedly stimulates the abilities to replicate and to commit to a neuronal lineage following prolonged exposure in cultured neural progenitor cells (NPCs) prepared from embryonic and adult rodent brains. Upregulation of transcript expression is found for one of the GLN transporter isoforms, Slc38a1, besides the promotion of both proliferation and neuronal commitment along with acceleration of the phosphorylation of mechanistic target of rapamycin (mTOR) and relevant downstream proteins, in murine NPCs cultured with theanine. Stable overexpression of Slc38a1 similarly facilitates both cellular replication and neuronal commitment in pluripotent embryonic carcinoma P19 cells. In P19 cells with stable overexpression of Slc38a1, marked phosphorylation is seen for mTOR and downstream proteins in a manner insensitive to further additional phosphorylation by theanine. Taken together, theanine would exhibit a novel pharmacological property to up-regulate Slc38a1 expression for activation of the intracellular mTOR signaling pathway required for neurogenesis after sustained exposure in undifferentiated NPCs in the brain. In this review, a novel neurogenic property of the green tea amino acid theanine is summarized for embryonic and adult neurogenesis with a focus on the endogenous amino acid GLN on the basis of our accumulating evidence to date.

Development of the basal hypothalamus through anisotropic growth.

The adult hypothalamus is subdivided into distinct domains: pre-optic, anterior, tuberal and mammillary. Each domain harbours an array of neurones that act together to regulate homeostasis. The embryonic origins and the development of hypothalamic neurones, however, remain enigmatic. Here, we summarise recent studies in model organisms that challenge current views of hypothalamic development, which traditionally have attempted to map adult domains to correspondingly located embryonic domains. Instead, new studies indicate that hypothalamic neurones arise from progenitor cells that undergo anisotropic growth, expanding to a greater extent than other progenitors, and grow in different dimensions. We describe in particular how a multipotent Shh/ Fgf10-expressing progenitor population gives rise to progenitors throughout the basal hypothalamus that grow anisotropically and sequentially: first, a subset displaced rostrally give rise to anterior-ventral/tuberal neuronal progenitors; then a subset displaced caudally give rise to mammillary neuronal progenitors; and, finally, a subset(s) displaced ventrally give rise to tuberal infundibular glial progenitors. As this occurs, stable populations of Shh+ive and Fgf10+ive progenitors form. We describe current understanding of the mechanisms that induce Shh+ive /Fgf10+ive progenitors and begin to direct their differentiation to anterior-ventral/tuberal neuronal progenitors, mammillary neuronal progenitors and tuberal infundibular progenitors. Taken together, these studies suggest a new model for hypothalamic development that we term the "anisotropic growth model". We discuss the implications of the model for understanding the origins of adult hypothalamic neurones.

Yin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner.

The transcription factor Yin Yang 1 (YY1) plays an important role in human disease. It is often overexpressed in cancers and mutations can lead to a congenital haploinsufficiency syndrome characterized by craniofacial dysmorphisms and neurological dysfunctions, consistent with a role in brain development. Here, we show that Yy1 controls murine cerebral cortex development in a stage-dependent manner. By regulating a wide range of metabolic pathways and protein translation, Yy1 maintains proliferation and survival of neural progenitor cells (NPCs) at early stages of brain development. Despite its constitutive expression, however, the dependence on Yy1 declines over the course of corticogenesis. This is associated with decreasing importance of processes controlled by Yy1 during development, as reflected by diminished protein synthesis rates at later developmental stages. Thus, our study unravels a novel role for Yy1 as a stage-dependent regulator of brain development and shows that biosynthetic demands of NPCs dynamically change throughout development.

Electroacupuncture Facilitates the Integration of Neural Stem Cell-Derived Neural Network with Transected Rat Spinal Cord.

The hostile environment of an injured spinal cord makes it challenging to achieve higher viability in a grafted tissue-engineered neural network used to reconstruct the spinal cord circuit. Here, we investigate whether cell survival and synaptic transmission within an NT-3 and TRKC gene-overexpressing neural stem cell-derived neural network scaffold (NN) transplanted into transected spinal cord could be promoted by electroacupuncture (EA) through improving the microenvironment. Our results showed that EA facilitated the cell survival, neuronal differentiation, and synapse formation of a transplanted NN. Pseudorabies virus tracing demonstrated that EA strengthened synaptic integration of the transplanted NN with the host neural circuit. The combination therapy also promoted axonal regeneration, spinal conductivity, and functional recovery. The findings highlight EA as a potential and safe supplementary therapeutic strategy to reinforce the survival and synaptogenesis of a transplanted NN as a neuronal relay to bridge the two severed ends of an injured spinal cord.

Amino acid composition of nanofibrillar self-assembling peptide hydrogels affects responses of periodontal tissue cells in vitro.

BACKGROUND: The regeneration of tissue defects at the interface between soft and hard tissue, eg, in the periodontium, poses a challenge due to the divergent tissue requirements. A class of biomaterials that may support the regeneration at the soft-to-hard tissue interface are self-assembling peptides (SAPs), as their physicochemical and mechanical properties can be rationally designed to meet tissue requirements. MATERIALS AND METHODS: In this work, we investigated the effect of two single-component and two complementary ß-sheet forming SAP systems on their hydrogel properties such as nanofibrillar architecture, surface charge, and protein adsorption as well as their influence on cell adhesion, morphology, growth, and differentiation. RESULTS: We showed that these four 11-amino acid SAP (P11-SAP) hydrogels possessed physico-chemical characteristics dependent on their amino acid composition that allowed variabilities in nanofibrillar network architecture, surface charge, and protein adsorption (eg, the single-component systems demonstrated an ~30% higher porosity and an almost 2-fold higher protein adsorption compared with the complementary systems). Cytocompatibility studies revealed similar results for cells cultured on the four P11-SAP hydrogels compared with cells on standard cell culture surfaces. The single-component P11-SAP systems showed a 1.7-fold increase in cell adhesion and cellular growth compared with the complementary P11-SAP systems. Moreover, significantly enhanced osteogenic differentiation of human calvarial osteoblasts was detected for the single-component P11-SAP system hydrogels compared with standard cell cultures. CONCLUSION: Thus, single-component system P11-SAP hydrogels can be assessed as suitable scaffolds for periodontal regeneration therapy, as they provide adjustable, extracellular matrix-mimetic nanofibrillar architecture and favorable cellular interaction with periodontal cells.

Proliferation and committed differentiation into dopamine neurons of neural stem cells induced by the active ingredients of radix astragali.

Neural stem cells (NSCs) are important cellular sources of transplantation therapies for Parkinson's disease. This study aimed to determine the effects of extracts of radix astragali on the proliferation and differentiation into dopamine (DA) neurons in NSCs. NSCs were dealt with astragaloside IV (ASI), astragalus polysaccharide (APS), and astraisoflavan (ASF), the main active ingredients of radix astragali. First, the results from cell-count kit-8 (CCK-8) assay showed that ASI, ASF, and APS had positive effects on the proliferation of NSCs. Next, we also confirmed the effects of ASI, APS, and ASF on BrdU and nestin by immunocytochemistry. Moreover, results from quantitative RT-PCR showed ASI, APS, and ASF could promote the expressions of tyrosine hydroxylase and dopamine transporter mRNA, which are specifically expressed in DA neurons. Simultaneously, sonic hedgehog (Shh), orphan nuclear hormone 1 (Nurr1), and pituitary homeobox 3 (Ptx3) are considered to motivate the formation of DA neurons. Our result showed ASI, APS, and ASF can also promote the expressions of Shh, Nurr1, and Ptx3 mRNAs. In conclusion, our study verifies that the active ingredients of radix astragali can promote the proliferation of NSCs and induce NSC differentiation toward DA neurons in vitro. These phenomena may occur through upregulation of Shh, Nurr1, and Ptx3 in the process of drug treatment.

Cellular toxicity driven by high-dose vitamin C on normal and cancer stem cells.

As a powerful antioxidant, vitamin C protects cells from oxidative damage by inhibiting production of free radicals. However, high levels of vitamin C shows cytotoxicity especially on cancerous cells through generating excessive ROS and blocking the energy homeostasis. Although the double-sided character of vitamin C has been extensively studied in many cell types, there is little research on the consequence of vitamin C treatment in stem cells. Here, we identified that high-dose vitamin C shows cellular toxicity on proliferating NSPCs. We also demonstrated that undifferentiated NSPCs are more sensitive to vitamin C-driven DNA damage than differentiated cells, due to higher expression of Glut genes. Finally, we showed that high-dose vitamin C selectively induces DNA damage on cancer stem cells rather than differentiated tumor cells, raising a possibility that vitamin C may be used to target cancer stem cells.

Seasonal reorganization of hypothalamic neurogenic niche in adult sheep.

Neurogenesis is the process by which new neurons are generated. This process, well established during development, persists in adulthood owing to the presence of neural stem cells (NSCs) localized in specific brain areas called neurogenic niches. Adult neurogenesis has recently been shown to occur in the hypothalamus, a structure involved in the neuroendocrine regulation of reproduction and metabolism, among others. In the adult sheep-a long-lived mammalian model-we have previously reported the existence of such a neurogenic niche located in the hypothalamic arcuate nucleus and the median eminence. In addition, in this seasonal species, the proliferation as well as neuroblasts production varies depending on the time of the year. In the present study, we provide a better characterization of the hypothalamic neurogenic niche by identifying the main components (NSCs, migrating cells, glial cells and blood vessels) using immunohistochemistry for validated markers. Then, we demonstrate the strong sensitivity of these various neurogenic niche components to the season, particularly in the arcuate nucleus. Further, using an electron microscopic approach, we reveal the cellular and cytoarchitectural reorganization of the arcuate nucleus niche following exposure to contrasting seasons. This study provides evidence that the arcuate nucleus and the median eminence contain two independent niches that react differently to the season. In addition, our results support the view that the cytoarchitectural organization of the sheep arcuate nucleus share comparable features with the structure of the subventricular zone in humans and non-human primates.

Lipocalin-2 regulates adult neurogenesis and contextual discriminative behaviours.

In the adult mammalian brain, newborn granule cells are continuously integrated into hippocampal circuits, and the fine-tuning of this process is important for hippocampal function. Thus, the identification of factors that control adult neural stem cells (NSCs) maintenance, differentiation and integration is essential. Here we show that the deletion of the iron trafficking protein lipocalin-2 (LCN2) induces deficits in NSCs proliferation and commitment, with impact on the hippocampal-dependent contextual fear discriminative task. Mice deficient in LCN2 present an increase in the NSCs population, as a consequence of a G0/G1 cell cycle arrest induced by increased endogenous oxidative stress. Of notice, supplementation with the iron-chelating agent deferoxamine rescues NSCs oxidative stress, promotes cell cycle progression and improves contextual fear conditioning. LCN2 is, therefore, a novel key modulator of neurogenesis that, through iron, controls NSCs cell cycle progression and death, self-renewal, proliferation and differentiation and, ultimately, hippocampal function.

A comparative study of the neural stem cell niche in the adult hypothalamus of human, mouse, rat and gray mouse lemur (Microcebus murinus).

The adult brain contains niches of neural stem cells that continuously add new neurons to selected circuits throughout life. Two niches have been extensively studied in various mammalian species including humans, the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus. Recently, studies conducted mainly in rodents have identified a third neurogenic niche in the adult hypothalamus. In order to evaluate whether a neural stem cell niche also exists in the adult hypothalamus in humans, we performed multiple immunofluorescence labeling to assess the expression of a panel of neural stem/progenitor cell (NPC) markers (Sox2, nestin, vimentin, GLAST, GFAP) in the human hypothalamus and compared them with the mouse, rat and a non-human primate species, the gray mouse lemur (Microcebus murinus). Our results show that the adult human hypothalamus contains four distinct populations of cells that express the five NPC markers: (a) a ribbon of small stellate cells that lines the third ventricular wall behind a hypocellular gap, similar to that found along the lateral ventricles, (b) ependymal cells, (c) tanycytes, which line the floor of the third ventricle in the tuberal region, and (d) a population of small stellate cells in the suprachiasmatic nucleus. In the mouse, rat and mouse lemur hypothalamus, co-expression of NPC markers is primarily restricted to tanycytes, and these species lack a ventricular ribbon. Our work thus identifies four cell populations with the antigenic profile of NPCs in the adult human hypothalamus, of which three appear specific to humans.

Hyperbaric oxygen promotes neural stem cell proliferation by activating vascular endothelial growth factor/extracellular signal-regulated kinase signaling after traumatic brain injury.

Hyperbaric oxygen (HBO) therapy and neural stem cell (NSC) transplantation can improve traumatic brain injury (TBI) clinically. This study aimed to investigate the mechanism of HBO promoting NSC proliferation and neurological recovery after TBI. Twenty-four Sprague-Dawley rats were divided randomly into three groups: a sham group, a TBI group (constructed using Feeney's free-fall method), and an HBO-treated TBI group. Neurological function was evaluated by Neurological Severity Scores on days 1, 3, and 7, and we found that TBI-induced poor neurological function was improved by HBO. On day 7 after TBI, we observed that TBI promoted NSC proliferation, migration to the lesion area, and the levels of vascular endothelial growth factor (VEGF), VEGFR2, Raf-1, MEK1/2, and phospho-extracellular signal-regulated kinase (ERK) 1/2 protein, which were further boosted by HBO, from immunohistochemistry, immunofluorescence, and Western blot experiments. In vitro, cell injury was applied to NSCs isolated from neonatal Sprague-Dawley rats by the Cell Injury Controller II system. Moreover, data from the BrdU Kit and Western blot showed that in-vitro HBO significantly accelerated NSC proliferation and the levels of proteins related to cell cycle and the VEGF/ERK pathway after cell injury, which was suppressed by the VEGFR2 inhibitor. Taken together, this study indicated that HBO may promote NSC proliferation by activating VEGF/ERK signaling and play a crucial role in neuroprotection after TBI.