Acute or chronic brain damage in adults frequently results in significant loss of neuronal tissue and persistent functional disability. A number of treatments have been developed over the last two decades to harness the regenerative potential of neural stem cells and the current destiny flexibility of neural cells in the nervous system to avoid tissue loss or improve structural and functional regeneration following damage. We examine current obstacles and limitations in stem cell-associated neural healing in the adult brain, as well as potential approaches for advancing experimental stem cell therapies into the clinic.

The brain is always at risk of injury, whether it is acute or chronic. The capacity for regeneration in the adult mammalian brain has long been thought to be severely limited when compared to other tissues such as the skin, liver, or intestines. As a result, the mammalian brain is unable to rebuild structures that have been lost due to harmful events such as ischemic stroke or traumatic brain injury. With acute or chronic injury, however, there is significant functional restoration due to the ability of surviving brain structures to take up at least some of the functions of destroyed tissues. This is seen, for example, in patients who have left-hemispheric strokes and may initially exhibit motor or sensory aphasi.

Brain repair by targeting endogenous neurogenesis One of these is the SVZ, which lines the lateral ventricles and is where NSCs give birth to newborn cells that migrate along the rostral migratory stream into the olfactory bulb (OB), where they differentiate into several types of olfactory neurons. In the rodent brain, SVZ/OB neurogenesis is relatively active, whereas in the human brain, the neurogenic activity of the SVZ appears to be very low or non-existent. In contrast, the hippocampus DG, where NSCs give rise to DG granule cells throughout life, is the second major neurogenic region.

Glial repair with neural stem Cells The destiny potential of endogenous NSCs also allows for targeting NSCs to assist glial cell replacement and eventual brain repair, in addition to techniques aimed at enhancing endogenous neurogenesis for neuronal repair in the context of acute or chronic illness. Demyelination in the mouse SVZ, for example, has been shown to result in increased NSC-derived oligodendrocyte production, which may aid in the remyelination of the wounded brain following a lesion. Induced production of oligodendrocytes (which are not produced by DG NSCs under normal conditions) could be used to induce remyelination of the DG circuitry in a variety of demyelinating disorders, including multiple sclerosis and epilepsy. However, possible therapeutic techniques aimed at using endogenous NSCs for glial repair are still being developed, and more research is needed.