Study: Human brain makes new cells to treat damage, disease

[Gaby]

From http://news.xinhuanet.com/english/2007-02/16/content_5746373.htm

BEIJING, Feb. 16 (Xinhuanet) -- Scientists have discovered that the human brain can manufacture fresh brain cells which may lead to a better way to treat brain damage and disease like Alzheimer's, Parkinson's and stroke,according to media reports Friday.

Neuroscientists from Auckland University and Carlsson Institute for Neuroscience in Sweden found a cell pathway through which the adult brain may repair itself. The report will be published as the cover story next week in the journal "Science."

These cells are born in one part of the brain and then migrate to the olfactory bulb, where smells are processed. They mature into neurons on the way.

Scientists have known that other animals, such as rats and mice, make new brain cells throughout their lives and there had been indirect evidence that humans beings could also.

Since humans have far more developed brains, searching for these cells has been harder than it was in rodents.

The Auckland-Sweden collaboration was the first to trace the path of the human "neurogenesis motorway".

"The excitement from this pathway is if we can try and develop an understanding of what makes these cells multiply and travel - if we could enhance this to help people who have brain cells die." Auckland University's Professor Richard Faull, one of the leaders of the eight-year study said.

He said that what they want to find now is a way to redirect the path of new cells to areas where cells are damaged or have died due to neurological diseases.

 

[zak]

I put in sight this thread of Gaby finally to add some other links.
Here those more or less relevant links:
Adult neurogenesis
Contents:

1 Neural Stem Cells
2 Maturation of New Neurons
2.1 Maturation of new neurons in the adult dentate gyrus
2.2 Maturation of new neurons in the adult olfactory bulb
2.3 Neuronal selection and survival
3 Regulation of Neurogenesis
4 Function of Neurogenesis
4.1 Hippocampus-dependent behavioral tasks
4.2 Olfactory bulb-dependent behavioral tasks
4.3 Computational impact of new neurons
5 Adult Neurogenesis in other Species
5.1 Birdsong system
5.2 Adult neurogenesis in Fish
6 References
7 Recommended reading
8 External links
9 See Also

http://scholarpedia.org/article/File:Adult_neurog.gif
Adult neurogenesis is the process of generating new neurons which integrate into existing circuits after fetal and early postnatal development has ceased. In most mammalian species, adult neurogenesis only appears to occur in the olfactory bulb and the hippocampus. In addition there is a high level of adult neurogenesis in the olfactory epithelium (considered part of the peripheral nervous system) where olfactory receptor neurons are constantly replaced. The process appears more widespread but still limited in other vertebrate classes, having been described in select brain regions of certain birds, fish and reptiles. Furthermore, many invertebrates and vertebrates have neural regenerative capacities that involve neurogenesis (such as tail regeneration in salamanders)

Neural Stem Cells
New neurons are generated throughout life from a population of dividing cells known as neural stem/progenitor cells (NPCs). Two criteria are typically used to define a cell as a stem cell:1) the potential of self-renewal and 2) the ability to give rise to multiple distinct cell types. NPCs isolated from the adult brain are classified as a ‘’multipotent’’ cell because they can differentiate into the the three main lineage cell types of the nervous system (neurons, astrocytes, and oligodendrocytes) when cultured in vitro. The evidence for multipotency of NPCs in vivo remains scant.

There are two neurogenic regions in the adult brain where under physiological conditions NPCs give rise to new neurons: (1) the subventricular zone of the lateral ventricles (SVZ) where NPCs generate cells that migrate into the olfactory bulb, and (2) the subgranular zone (SGZ) of the dentate gyrus (DG) where new granule cells become integrated into the local neuronal network ( Figure 1). For those two regions several types of dividing progenitors were identified . The “type-1” cells (or ‘B’ cells in the SVZ) are similar to the radial glial cells observed during development, and have a morphology and physiology similar to mature astrocytes. Although they reside in the SGZ, they extend processes up into the molecular layer. Type-1 and B cells are relatively quiescent. In contrast “Type-2” cells (or ‘C’ cells in the SVZ),have a high proliferative activity but have a small roundish morphology. The current hypothesis is that Type-2 cells (or 'C' cells) give rise to Type-3 (or A cells) representing neuronally committed neuroblasts.

NPCs are not limited to neurogenic regions of the brain, rather their proliferation can be observed in most CNS regions, especially after injury. However, in these other regions it appears that neurogenesis is actively repressed by the local environment - NPCs from non-neurogenic regions have been observed to give rise to neurons when transplanted into the hippocampus. Some evidence indicates that this effect is mediated by the local astrocyte populations.

NPCs have historically been labeled in the brain by the addition of a proliferation marker, such as 3H-thymadine or bromodeoxyuridine (BrdU; Figure 2, bottom). Immunohistochemistry for BrdU can be combined with the detection of mature markers to identify the phenotype of the newborn cells. Recently, several molecular techniques for labeling adult-born cells have been developed, including transgenic mice with GFP driven by a stem cell gene's promoter (i.e., Nestin-GFP; Figure 2, top left) and retroviral labeling ( Figure 2, top right). BrdU labeling has been used to definitively show that new neurons are incorporated into the dentate gyrus and olfactory bulb of the adult human brain (Eriksson et al., 1998; Curtis et al., 2007).

For a detailed review of NPCs in vitro and in vivo, see .

Maturation of New Neurons
Adult neurogenesis is unique from developmental neurogenesis because the new neurons must integrate into an established, functioning network. Much of the present knowledge about neuronal development in adult neurogenesis has been reviewed by Kempermann et al.(2004), Ming and Song (2005). Abrous et al. (2005), and Zhao et al.(2008).

Maturation of new neurons in the adult dentate gyrus
The process of adult hippocampal neurogenesis is entirely confined to the dentate gyrus. Local progenitor cells in the SGZ undergo neuronal differentiation, and may show a limited migration into the GCL. The speed of maturation is likely experience dependent, and varies between neurons. Approximate duration of a number of distinct post-mitotic developmental phases of newborn granule cells are listed here. Figure 3 shows a scematic of the anatomical phases of granule cell growth.
1 Local GABA: (Less than 1 week old) Immature neurons have neurite outgrowth, but often not polarized towards molecular layer. Few or no synapses, but sensitive to locally diffuse GABA, which is depolarizing.
2 Synaptic GABA: (1 to 2 weeks old) Dendrites begin to extend into molecular layer (no spines) and axons can be observed in hilus. Synaptic GABA inputs can be observed, which is still excitatory. Glutamatergic inputs are not present. Immature action potentials can be observed when cells are directly stimulated.
3 Spine formation onset and axon outgrowth: (2 weeks old). By about 16 days neurons begin to develop spines in the molecular layer. GABA transitions to inhibitory around this time. By 17 days, new axons (mossy fibers) can be observed forming functional connections onto downstream hilar neurons and CA3 pyramidal cells.
4 Functionally immature neurons (~3 weeks to 2 months) Spine formation is gradual, with neurons progressively increasing their dendritic arborization and connections. Mossy fibers continue to mature, with boutons on CA3 neurons growing considerably by 28 days. Neurons still have unique physiological properties, including increased LTP, and different resistance, capacitance and resting potentials.
5 Fully mature neurons (> 2 months old). Newborn neurons eventually become physiologically indistinguishable from fully mature neurons.

Recent work using immediate early genes such as c-fos, Zif268, and Arc as putative markers of neuronal activity have shown that water maze training (Kee et al., 2007) or exposure to an enriched environment (Tashiro et al., 2007) during this maturation process will cause these neurons to be more responsive upon reexposure to the same condition several weeks later.

Maturation of new neurons in the adult olfactory bulb
In contrast to adult neurogenesis in the dentate gyrus, cells that were born in the SVZ migrate a long distance into their target area, the olfactory bulb. This long migration gives olfactory neurogenesis a different timescale from DG neurogenesis.

1 Migration: (2-6 Days) Newborn cells migrate in chains along the rostral migratory stream (RMS), a structure maintained by specialized astrocytes. After the newborn neurons reach the middle of the OB they detach from the chains and migrate radially.
2 Neuronal Differentiation: (15-30 Days) After immature neurons reach the OB, they begin to differentiate into two different types of local interneurons. Over 95% differentiate into GABA-ergic granule neurons whereas the remainder become periglomerular neurons expressing either GABA and/or dopamine as neurotransmitter. Newborn granule cells can be distinguished into cells with dendrites that do not extend beyond the mitral cell layer and other cells that possess non-spiny dendrites reaching into the external plexiform layer.
3 Integration into network: (15 -30 Days) Newborn granule cells and periglomerular neurons become integrated into the OB circuitry and respond to olfactory stimuli.

Neuronal selection and survival
One critical aspect of adult neurogenesis is the selection process. While large numbers of new neurons are born to the OB and DG, only a fraction of these cells survive. In the dentate gyrus, approximately half of the newborn neurons die within 2 weeks of birth, but this number is heavily regulated by various factors. In contrast to newborn DG neurons the selection process in the OB appears to be later in the development process, when young neurons with extended dendrites already covered with spines are susceptible to cell death.

Regulation of Neurogenesis
The "rediscovery" of neurogenesis in the 1990's was due in large part to the observation that the levels of new neurons in the adult hippocampus are modulated by a range of factors, including stress (Gould et al., 1990), aging (Kuhn et al., 1996), environment (Kempermann et al., 1998), and activity (van Praag et al., 1999). Numerous drugs and behaviors have since been shown to affect the levels of new neurons in the brain. Modulation of neurogenesis typically occurs in one of two ways in vivo – either the modulator changes the levels of proliferation of NPCs, or the effect is on the survival of the new neurons. The most studied modulators have been summarized in the following tables. See Ming and Song (2005) and Abrous et al.(2005) for more details.

Table of Dentate Gyrus Neurogenesis Regulators
Table of Olfactory Bulb Neurogenesis Regulators http://scholarpedia.org/article/Adult_neurogenesis/neurogenesis_table#Dentate_Gyrus

Several neuro-psychiatric conditions have been associated with altered rates of neurogenesis in animal models, including Alzheimer’s disease, temporal-lobe epilepsy, ischemia, and depression. In each of these cases, it remains unclear whether perturbed neurogenesis is a symptom of the disorder or has a causal role. Aging also has a robust effect on neurogenesis, with levels of new neurons decreasing in later stages of life. The marked decrease occurs fairly early and neurogenesis is maintained at a very low level for most of the life span.

Function of Neurogenesis
While the observation and characterization of neurogenesis has been robust, the role of adding new neurons on a region’s function has remained elusive in most cases. Nonetheless, because neurons are integrating into regions of relatively well described circuitry and function, several behavioral and computational ideas have been explored.

Hippocampus-dependent behavioral tasks
Several techniques to reduce adult neurogenesis have been used to look at the process’s effect on hippocampal function. These have included x-ray irradiation, anti-proliferative drugs (MAM) and molecular knock-downs. A range of hippocampus-dependent behaviors have been tested with mixed results (see Deng et al., 2010 for a review). Trace eyeblink conditioning was shown to be affected in MAM experiments, and contextual fear conditioning was impaired following irradiation and genetic ablation of adult neurogenesis. Morris Water Maze (MWM) testing has shown inconsistent results in several paradigms, with some experimenters seeing deficits in short-term retention, others in long-term retention, and others no discernable differences at all. Furthermore, set of behavioral studies have demonstrated that neurogenesis may have a role in the pattern separation function of the dentate gyrus (Clelland et al., 2009). Finally, a recent study has suggested that new neurons may be important in memory consolidation (Kitamura et al., 2009).

In addition to its presumed role in memory, the correlation of neurogenesis levels to stress has suggested a role in anxiety-related behaviors. For example, fluoxetine (the active compound in Prozac) is not effective as an anti-depressant in mice without adult neurogenesis due to irradiation.

Olfactory bulb-dependent behavioral tasks
The function of the olfactory pathway can be tested with a variety of behavioral tasks that test odor discrimination or odor learning. Using transgenic mice with reduced OB neurogenesis it could be shown that new OB neurons appear to be critically involved in odor discrimination. At the same time odor discrimination learning itself increases the survival of newborn OB neurons. The same effect on survival has been found using odor enrichment resulting in improved odor memory.

Computational impact of new neurons
Because the dentate gyrus is the entry structure to the hippocampus, which has a substantial history of neural network modeling, several non-exclusive computational functions have been suggested for neurogenesis. These have arisen from both theoretical and computational modeling ventures. For a more detailed review of the theoretical functions of adult neurogenesis, see Aimone, Deng, and Gage; 2010.

Increase of hippocampal memory capacity – several models predict network capacity will increase with neurogenesis, but Becker’s model (2005) explores the idea in a full hippocampal model. Becker predicts that the increase in possible sparse codes due to new neurons increases the quality of memory formation in downstream hippocampal regions.
Reduction of interference between new and older memories – Wiskott and colleagues (2005) propose that the presence of new neurons helps the dentate gyrus network respond to changing inputs. Specifically, their model suggests that without neurogenesis, the hippocampal network will suffer from “catastrophic interference,” leaving the network unable to effectively encode new memories.
Encoding time in memories – Aimone et al. (2006; 2009) suggest that the different physiological properties of immature neurons will bias the sparse coding function of the dentate gyrus, possibly providing a link between memory associations formed in the recurrent CA3 network.

Olfactory bulb neurogenesis has not been as extensively studied computationally, possibly because the olfactory bulb circuit does not have the history of modeling that the hippocampus has. Cecchi et al.’s (2001) theoretical study of OB neurogenesis suggests functional roles similar to those suggested for newborn neurons in the dentate gyrus. Cecchi’s results suggest that random incorporation of new neurons with activity-dependent survival will maximize the discrimination of odors presented to the network.

Adult Neurogenesis in other Species
Higher levels of adult neurogenesis are observed in many non-mammalian species, many of which retain regenerative neurogenesis capabilities throughout life. Neurogenesis in the course of normal adult function has been best described in birds and fish.

Birdsong system
Adult neurogenesis in birds has been most heavily characterized in the higher vocal center (HVC) area of the birdsong system, although it has been observed in other regions, including the avian hippocampus. Bird song neurogenesis is sometimes characterized by very high levels of seasonal variation – with more neurons appearing in months which have higher levels of song learning. For example, in the canary brain, there is a high level of seasonal cell death of RA projecting HVC neurons in males - in low-neurogenesis, non-learning periods, the HVC is a fraction of the size of learning seasons. Many of the underlying regulators of this process have been elucidated, including seasonal variations in testosterone.

Although this song system is not present in mammals, bird song neurogenesis is an active field of study because it is of the region’s clear role in a well-studied motor learning process. The specific role of new neurons in bird song learning still unclear, but it is interesting to note that the neurogenic cells in HVC have been implicated in sparse coding, just as dentate gyrus cells in the mammalian hippocampus.

Adult neurogenesis in Fish
Fish have many proliferative zones throughout the brain, which are thought to be able to provide neurons to almost any region of the brain (Zupanc, 2006). Consistent with other vertebrates, the olfactory bulb and dorsal telencephalon (the fish equivalent of the hippocampus) have robust neurogenesis, though most of the new neurons are found in the cerebellum. Because of this widespread proliferation, the overall rate of neurogenesis appears several orders of magnitude higher in fish than in rodents – with an estimate over about 0.2% of the total cells in the brain cells proliferating at any given time.
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More things on adult neurogenesis and neurogenesis:

Summary of the signalling pathways in the neural stem cell microenvironment

Implications

Role in learning
The functional relevance of adult neurogenesis is uncertain,[45] but there is some evidence that hippocampal adult neurogenesis is important for learning and memory.[46] Multiple mechanisms for the relationship between increased neurogenesis and improved cognition have been suggested, including computational theories to demonstrate that new neurons increase memory capacity,[47] reduce interference between memories,[48] or add information about time to memories.[49] Experiments aimed at ablating neurogenesis have proven inconclusive, but several studies have proposed neurogenic-dependence in some types of learning,[50] and others seeing no effect.[51] Studies have demonstrated that the act of learning itself is associated with increased neuronal survival.[52] However, the overall findings that adult neurogenesis is important for any kind of learning are equivocal.

Alzheimer's disease
Some studies suggest that decreased hippocampal neurogenesis can lead to development of Alzheimer's disease (AD).[53] Yet, others hypothesize that AD patients have increased neurogenesis in the CA1 region of Ammon's horn (the principal region of AD hippocampal pathology) in order to compensate for neuronal loss.[54] While the exact nature of the relationship between neurogenesis and Alzheimer's disease is unknown, insulin-like growth factor 1-stimulated neurogenesis produces major changes in hippocampal plasticity and seems to be involved in Alzheimer's pathology.[55] Allopregnanolone, a neurosteroid, aids the continued neurogenesis in the brain. Levels of allopregnanolone in the brain decline in old age and Alzheimer's disease.[56] Allopregnanolone has been shown through reversing impairment of neurogenesis to reverse the cognitive deficits in a mouse model of Alzheimer's disease.[57] Eph receptors and ephrin signaling have been shown to regulate adult neurogenesis in the hippocampus and have been studied as potential targets to treat some symptoms of AD.[58] Molecules associated with the pathology of AD, including ApoE, PS1 and APP, have also been found to impact adult neurogenesis in the hippocampus

Role in schizophrenia
Studies suggest that people with schizophrenia have a reduced hippocampus volume, which is believed to be caused by a reduction of adult neurogenesis. Correspondingly, this phenomenon might be the underlying cause of many of the symptoms of the disease. Furthermore, several research papers referred to four genes, dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), disrupted in schizophrenia 1 (DISC1), and neuregulin 1 receptor (ERBB4), as being possibly responsible for this deficit in the normal regeneration of neurons.[60][61] Similarities between depression and schizophrenia suggest a possible biological link between the two diseases. However, further research must be done in order to clearly demonstrate this relationship

Adult Neurogenesis and Major Depressive Disorder
Research indicates that adult hippocampal neurogenesis is inversely related to Major Depressive Disorder (MDD).[63] Neurogenesis is decreased in the hippocampus of animal models of major depressive disorder, and many treatments for the disorder, including antidepressant medication and electroconvulsive therapy, increase hippocampal neurogenesis. It has been theorized that decreased hippocampal neurogenesis in individuals with major depressive disorder may be related to the high levels of stress hormones called glucocorticoids, which are also associated with the disorder. The hippocampus instructs the hypothalamic-pituitary-adrenal axis to produce less glucocorticoids when glucocorticoid levels are high. A malfunctioning hippocampus, therefore, might explain the chronically high glucocorticoid levels in individuals with major depressive disorder. However, some studies have indicated that hippocampal neurogenesis is not lower in individuals with major depressive disorder and that blood glucocorticoid levels do not change when hippocampal neurogenesis changes, so the associations are still uncertain

Stress and depression
Many now believe stress to be the most significant factor for the onset of depression, aside from genetics. As discussed above, hippocampal cells are sensitive to stress which can lead to decreased neurogenesis. This area is being considered more frequently when examining the causes and treatments of depression. Studies have shown that removing the adrenal gland in rats caused increased neurogenesis in the dentate gyrus.[64] The adrenal gland is responsible for producing cortisol in response to a stressor, a substance that when produced in chronic amounts causes the down regulation of serotonin receptors and suppresses the birth of neurons.[65] It was shown in the same study that administration of corticosterone to normal animals suppressed neurogenesis, the opposite effect.[64] The most typical class of antidepressants administered for this disease are selective serotonin reuptake inhibitors (SSRIs)[66] and their efficacy may be explained by neurogenesis. In a normal brain, an increase in serotonin causes suppression of the corticotropin-releasing hormone (CRH) through connection to the hippocampus. It directly acts on the paraventricular nucleus to decrease CRH release and down regulate norepinephrine functioning in the locus coeruleus.[64] Because CRH is being repressed, the decrease in neurogenesis that is associated with elevated levels of it is also being reversed. This allows for the production of more brain cells, in particular at the 5-HT1a receptor in the dentate gyrus of the hippocampus which has been shown to improve symptoms of depression. It normally takes neurons approximately three to six weeks to mature,[67] which is approximately the same amount of time it takes for SSRIs to take effect. This correlation strengthens the hypothesis that SSRIs act through neurogenesis to decrease the symptoms of depression. Some neuroscientists have expressed skepticism that neurogenesis is functionally significant, given that a tiny number of nascent neurons are actually integrated into existing neural circuitry. However, a recent study used the irradiation of nascent hippocampal neurons in rodents to demonstrate that neurogenesis is required for antidepressant efficacy.[68]

Adult-born neurons appear to have a role in the regulation of stress.[69][70] Studies have linked neurogenesis to the beneficial actions of specific antidepressants, suggesting a connection between decreased hippocampal neurogenesis and depression.[71][72] In a pioneer study, scientists demonstrated that the behavioral benefits of antidepressant administration in mice is reversed when neurogenesis is prevented with x-irradiation techniques.[73] In fact, newborn neurons are more excitable than older neurons due to a differential expression of GABA receptors.[74] A plausible model, therefore, is that these neurons augment the role of the hippocampus in the negative feedback mechanism of the HPA-axis (physiological stress) and perhaps in inhibiting the amygdala (the region of brain responsible for fearful responses to stimuli).[vague] Indeed, suppression of adult neurogenesis can lead to an increased HPA-axis stress response in mildly stressful situations.[69] This is consistent with numerous findings linking stress-relieving activities (learning, exposure to a new yet benign environment, and exercise) to increased levels of neurogenesis, as well as the observation that animals exposed to physiological stress (cortisol) or psychological stress (e.g. isolation) show markedly decreased levels of newborn neurons. Interestingly, under chronic stress conditions, the elevation of newborn neurons by antidepressants improves the hippocampal-dependent control on the stress response; without newborn neurons, antidepressants are unable to restore the regulation of the stress response and recovery becomes impossible.[70]

Some studies have hypothesized that learning and memory are linked to depression, and that neurogenesis may promote neuroplasticity. One study proposes that mood may be regulated, at a base level, by plasticity, and thus not chemistry. Accordingly, the effects of antidepressant treatment would only be secondary to change in plasticity.[75] However another study has demonstrated an interaction between antidepressants and plasticity; the antidepressant fluoxetine has been shown to restore plasticity in the adult rat brain.[76] The results of this study imply that instead of being secondary to changes in plasticity, antidepressant therapy could promote it.

Effects of sleep reduction
One study has linked lack of sleep to a reduction in rodent hippocampal neurogenesis. The proposed mechanism for the observed decrease was increased levels of glucocorticoids. It was shown that two weeks of sleep deprivation acted as a neurogenesis-inhibitor, which was reversed after return of normal sleep and even shifted to a temporary increase in normal cell proliferation.[77] More precisely, when levels of corticosterone are elevated, sleep deprivation inhibits this process. Nonetheless, normal levels of neurogenesis after chronic sleep deprivation return after 2 weeks, with a temporary increase of neurogenesis.[78] While this is recognized, overlooked is the blood glucose demand exhibited during temporary diabetic hypoglycemic states. The American Diabetes Association amongst many documents the pseudosenilia and agitation found during temporary hypoglycemic states. Much more clinical documentation is needed to competently demonstrate the link between decreased hematologic glucose and neuronal activity and mood.

Possible use in treating Parkinson's disease
Parkinson's disease is a neurodegenerative disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Transplantation of fetal dopaminergic precursor cells has paved the way for the possibility of a cell replacement therapy that could ameliorate clinical symptoms in affected patients.[79] In recent years, scientists have provided evidence for the existence of neural stem cells with the potential to produce new neurons, particularly of a dopaminergic phenotype, in the adult mammalian brain.[80][81][82] Experimental depletion of dopamine in rodents decreases precursor cell proliferation in both the subependymal zone and the subgranular zone.[83] Proliferation is restored completely by a selective agonist of D2-like (D2L) receptors.[83] Neural stem cells have been identified in the neurogenic brain regions, where neurogenesis is constitutively ongoing, but also in the non-neurogenic zones, such as the midbrain and the striatum, where neurogenesis is not thought to occur under normal physiological conditions.[79] Newer research has shown that there in fact is neurogenesis in the striatum.[84] A detailed understanding of the factors governing adult neural stem cells in vivo may ultimately lead to elegant cell therapies for neurodegenerative disorders such as Parkinson's disease by mobilizing autologous endogenous neural stem cells to replace degenerated neurons

Traumatic Brain Injury
Traumatic brain injuries vary in their mechanism of injury, producing a blunt or penetrating trauma resulting in a primary and secondary injury with excitotoxicity and relatively wide spread neuronal death. Due to the overwhelming number of traumatic brain injuries as a result of the War on Terror, tremendous amounts of research have been placed towards a better understanding of the pathophysiology of traumatic brain injuries as well as neuroprotective interventions and possible interventions prompting restorative neurogenesis. Hormonal interventions, such as progesterone, estrogen, and allopregnanolone have been examined heavily in recent decades as possible neuroprotective agents following traumatic brain injuries to reduce the inflammation response stunt neuronal death.[85][86][87][88] In rodents, lacking the regenerative capacity for adult neurogenesis, the activation of stem cells following administration of α7 nicotinic acetylcholine receptor agonist, PNU-282987, has been identified in damaged retinas with follow-up work examining activation of neurogenesis in mammals after traumatic brain injury.[89] Currently, there is no medical intervention that has passed phase-III clinical trials for use in the human population

...
https://en.wikipedia.org/wiki/Neurogenesis
https://en.wikipedia.org/wiki/Adult_neurogenesis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106107/
http://www.jneurosci.org/content/22/3/614.long

If you can read only one, read this one:Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior
Without forget this one: The Timing for Neuronal Maturation in the Adult Hippocampus Is Modulated by Local Network Activity/ http://www.jneurosci.org/content/31/21/7715.long
And of course this last one: GABAergic Control of Adult Hippocampal Neurogenesis in Relation to Behavior Indicative of Trait Anxiety and Depression States/ http://www.jneurosci.org/content/27/14/3845

To go further:
Depression, Antidepressants, and Neurogenesis: A Critical Reappraisal
Infantile amnesia: A neurogenic hypothesis

More links:
https://www.salk.edu/search-results/?q=neurogenesis
http://www.mhs.biol.ethz.ch/utils/search.html?search=neurogenesis&language=en
https://sites.google.com/site/bradaimone/

Now let's taking a look to some videos:

http://<iframe width="560" height="...w="encrypted-media" allowfullscreen></iframe>

TEDxOrlando - Wendy Suzuki - Exercise and the Brain/ https://www.youtube.com/watch?v=LdDnPYr6R0o

Neurogenesis - Grow New Brain Cells With Exercise/ https://www.youtube.com/watch?v=h4NfYd4wq7o

http://<iframe width="560" height="...w="encrypted-media" allowfullscreen></iframe>

And: https://www.salk.edu/news-release/can-hear-now-ensuring-good-cellular-connections-brain/