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Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.

Objective: To explore whether hypoxic condition could promote the olfactory mucosa mesenchymal stem cells (OM-MSCs) to differentiate into neurons with the olfactory ensheathing cells (OECs) supernatant and the potential mechanisms.
 Methods: The OM-MSCs and OECs were isolated and cultured, and they were identified by flow cytometry and immunofluorescence. The OM-MSCs were divided into three groups: a 3%O2+ HIF-1α inhibitors (lificiguat: YC-1) + OECs supernatant group (Group A) , a 3%O2 + OECs supernatant group (Group B) and a 21%O2 + OECs supernatant group (Control group). The neurons, which were differentiated from OM-MSCs, were assessed by immunofluorescence test. The mRNA and protein expression of hypoxia-inducible factor-1α (HIF-1α), βIII-tubulin and glial fibrillary acidic portein (GFAP) were detected by quantitative polymerase chain reaction (Q-PCR) and Western blot. The potassium channels were analyzed by patch clamp.
 Results: The neurons differentiated from OM-MSCs expressed the most amount of βIII-tubulin, and the result of Q-PCR showed that HIF-1α expression in the Group B was significantly higher than that in the other groups (all P<0.05). Western blot result showed that the βIII-tubulin protein expression was significantly higher and GFAP protein expression was obviously decreased in the Group B (both P<0.05). The patch clamp test confirmed that the potassium channels in the neurons were activated.
 Conclusion: Hypoxic condition can significantly increase the neuronal differentiation of OM-MSCs by the OECs supernatant and decrease the production of neuroglia cells, which is associated with the activation of HIF-1 signal pathway.

Objective: To investigate whether intracerebral hemorrhage (ICH) can promote neurogenesis in the dentate gyrus (DG) of rat hippocampus., Methods: Western blot analysis, immunohistochemical staining, and immunofluorescent double labeling combined with confocal microscope were used to detect neurogenesis in the DG of the hippocampus in rats after ICH., Results: The expression of DCX protein in the ipsilateral DG of the hippocampus was enhanced in the rats 1 day after ICH (0.202∓0.062) as compared with that in normal rats (0.127∓0.088), reaching the peak level at 14 days (0.771∓0.108, P<0.01) and beginning to decrease at 28 days (0.582∓0.121, P<0.01). Meanwhile, DCX-positive cells and BrdU-positive cells, and DCX/BrdU double-labeled cells were detected in the DG of the hippocampus. Compared with those in the control group, BrdU/NeuN double-labeled cells were markedly increased in the granular cell layer of the DG at 28 days after ICH (1.808∓1.020 vs 5.654∓1.671, P<0.01)., Conclusion: ICH can promote neurogenesis in the DG of rat hippocampus.

G-protein-coupled receptor 17 (GPR17), an originally orphan receptor, was identified as a new uracil nucleotides/cysteinyl leukotriene receptor. However, whether GPR17 is really classified as a leukotriene receptor is a matter deserving further investigation. GPR17 is involved in many physiological and pathological processes including brain injury, spinal cord injury, and oligodendrocyte differentiation. GPR17 may become a new therapeutic target in these diseases. In this article, the research progress on the pharmacology and pathophysiological roles of GPR17 is reviewed.

Mammalian neurogenesis is a highly complicated process with programmed morphology and function evolution. Polarity, a basic characteristic in neurogenesis, is controlled by regulating proteins such as the partition defective (Par) proteins. Par polarity complex is the most investigated Par protein among these polarity proteins. There are developmental dynamic changes during neurogenesis for the protein distribution and content, which are related to the junction establishment, polarity formation, synaptogenesis, and neuronal migration. Moreover, Par complex is considered to affect the developmental fate of neural precursors. This study summarizes the advances of the protein cellular location, function, and mechanism in embryal neocortex and cultured neuron.

Adult neurogenesis had been confirmed in rodents and other mammals for decades. The mechanisms underlying neurogenesis have been investigated extensively in recent years. Microglial cells, an immuno-cell in the central nervous system, have been found playing important roles in modulating the process of adult neurogenesis. The inflammatory microenvironment contributed by microglia are harmful to the survival of new born neurons. On the other hand, by interacting with T cells, microglia could act as a trophic factor for neurogenesis, most possibly by releasing growth factors. We reviewed the progress on how microglia regulating adult neurogenesis in variant pathological conditions. To understand the relationship between microglia and neurogenesis will help us to approach for promising therapeutic strategy for neuronal injury.

Injured adult spinal cord neurons are usually unable to regenerate their axons due to the inhibitory environment and low intrinsic regenerative capability. One of the main strategies to promote spinal cord regeneration is blocking and/or neutralizing the inhibitory factors or their common inhibitory signal pathway. However, overcoming inhibition alone is insufficient to cause extensive regeneration when neurons' intrinsic growth state has not been activated. Therefore, it becomes one of the most interested targets for promoting spinal cord regeneration that how to enhance adult neurons' intrinsic growth capability, such as elevating adult neuron cAMP/PKA level, blocking Rho/ROCK pathway, modulating transcriptional factors etc., such that they no longer response to inhibitory environment. In this paper we will review the current research findings and recent progresses in this field.

The neuropeptid galanin is widely expressed in the central nervous system and has a diverse range of physiological effects including food intaking, arousal/sleep, nociception and reproduction. In this study, expression of galanin and galanin receptors (GalR1 and GalR2) mRNA were identified not only in the neurogenisis regions including subventricular zone (SVZ), rostral migratory stream (RMS) and dentate gyrus (DG) of adult mice but also in the SVZ-derived neural stem cell (NSC) culture. Here, we also showed that the addition of galanin and GalR2-specific agonist Gal2-11 to wild-type or GALKO NSCs under differentiation condition significantly promote the neuritogenesis and increase the length of neurites on the betaIII-tubulin positive cells. This effect could be reduced by treatment of the galanin antagonist M35. These results indicate that galanin and its receptors might regulate neurite extension in differentiating neural stem cells and even participate in the development of the nervous system.

Astrocytes can regulate synaptic transmission by releasing gliotransmitter, and also can promote synaptogenesis and neurogenesis by releasing estrogen, thrombospondins, IL-1beta and IL-6. Astrocytes may play critical roles in neural nutrition and neuroprotection, so that it might be a new target for treatment of certain central nervous system diseases.

Vascular endothelial growth factor (VEGF), originally discovered in tumor cells, is an angiogenic factor essential for new blood vessel formation during embryogenesis and in many pathological conditions. There is a growing body of evidence that VEGF can act directly on neurons and plays a new role as a neuroprotective factor via multiple mechanisms. Moreover, VEGF modulates neurogenesis in constitutive neurogenic and non-neurogenic regions of adult mammalian brains, which is a promising therapeutic strategy for neuronal replacement in traumatic brain injury and neurodegenerative diseases. Here, we mainly reviewed the neuroprotection of VEGF against ischemic brain injury and its mechanisms.

Objective: Seizures occur more frequently in the neonatal period than at any other time in life. A controversy which has been debated for the recent years is whether recurrent neonatal seizures can lead to long-term adverse consequences or are simply a reflection of underlying brain dysfunction and are not intrinsically harmful. Despite numerous clinical observations showed that seizures may be detrimental to the developing brain, the pathological mechanism has not yet been completely understood. The goal of this study was to investigate what effect was induced by recurrent seizures in neonatal rats on dentate granule cell neurogenesis., Methods: Sixty-four neonatal Wistar rats were randomly divided into seizure group (n = 40) and control group (n = 24). The rats of seizure group were subjected to three times of pilocarpine injections intraperitonealy at postnatal day 1 (P1), 4 (P4) and 7 (P7). Neonatal rats of the control group were given saline injection (i.p.) at the same time points. The rat were sacrificed separately at the next four time points: immediately after the third seizure (P7), the fourth day after the seizure (P11), the fourteenth day (P21) and the forty fifth day (P52), corresponding control group rats were killed accordingly. The rats in both seizure and control groups were given bromodeoxyuridine (BrdU) injection 36 hours before sacrifice to indicate newly generated cells. Brain tissue sections were prepared and subjected to Nissl staining for neuronal loss, by BrdU labeling for cell proliferation and by BrdU + NF200 (neurofilament 200) double labeling for the identification of the newly formed cells., Results: The numbers of BrdU-labeled cells were age-dependent in the control group, decreased with age, and their morphorlogy and distribution changed (P < 0.01). BrdU-labeled cells decreased significantly in the seizure group compared with the matched controls at P7 and P11 (P < 0.01), while at P21 there was no significant difficence between the two groups. On the contrary, BrdU-labeled cells increased significantly in the seizure group compared with the matched controls at P52 (P < 0.01). Most BrdU-labeled cells in granular cell layer (GCL) of both seizure group and control group coexpressed NF200., Conclusion: Recurrent seizures during neonatal period lead to decreased neurogenesis at the early stage after the third seizure, and at later time points increase of neurogenesis. Most of newly generated cells can differentiate into neurons.

Objective: Data accumulated over the past years have led to widespread recognition that neurogenesis, the emergence of new neurons, persists in the hippocampal dentate gyrus of the adult mammalian brain, and can be increased by seizures in multiple models. Also, aberrant reorganization of dentate granule cell axons, the mossy fiber sprouting, occurs in human temporal lobe epilepsy and rodent epilepsy models. However a number of studies suggest that the immature brain is less vulnerable to the morphologic alteration of hippocampus after seizures. The goal of this study was to determine whether the seizures can induce dentate granule cell neurogenesis and mossy fiber sprouting in the immature rat., Methods: Seizures was elicited by unilateral microinfusion of kainic acid (KA, 1 micro g) into the amygdula at postnatal day 15 (P15). Rat pups were given bromodeoxyuridine (BrdU) intraperitoneally on day 5 after KA administration and killed 7 d or 21 d later. The brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using neuron-specific, early differentiation marker TuJ1 (betaIII tubulin) or granule-specific marker CaBP (calcium-binding protein calbindin D28k) as well as glia-specific marker GFAP (glial fibrillary acidic protein). Mossy fiber sprouting in intermolecular layer and CA3 subfield was assessed in Timm-stained sections both 1 month and 3 months after KA administration by using a rating scale and density measurement., Results: The dentate BrdU-immunoreactive cells of the KA-treated rats increased significantly compared with those of control rats on day 7 and 21 after BrdU administration (7 d: 244 +/- 15 vs. 190 +/- 10; 21 d: 218 +/- 19 vs. 133 +/- 12, P < 0.05). Approximately 80.2% and 78.7% of BrdU-labeled cells coexpressed TuJ1 in KA-treated rats and control rats on day 7 after BrdU respectively (P > 0.05). On 21 d after BrdU, 60.2% and 58.2% of dentate BrdU-labeled cells coexpressed GaBP in KA-treated rats and control rats respectively (P > 0.05). GFAP colocalized with 3%-5% dentate BrdU-labeled cells in the rats of both groups on day 7 and 21 after BrdU. It was also demonstrated that status epilepticus at P15 did not result in any detectable mossy fiber sprouting within the hippocampus both 1 month and 3 months after KA administration., Conclusions: KA induced seizures can increase granule cell neurogenesis in the immature rat. Most of newly appeared cells migrate from subgranular proliferation zone (SGZ) into granule cell layer, the hilus as well as the molecular layer, and there they can differentiate into granule neurons. These observations also indicate that there is an early developmental resistance to seizure-induced mossy fiber sprouting in the immature brain.