Stem Cells and Stroke Recovery
Those patients who are fortunate enough to survive a stroke, leave the hospital, complete acute rehabilitation therapy, and return home enter a chronic phase of the disorder in which improvement may continue for weeks to months. Improvement proceeds via mechanisms that are poorly understood, but its occurrence implies continued plasticity of the nervous system, which might be exploited in treatment.
One approach that could enhance long-term recovery from stroke is based on partial reconstitution of the damaged portion of the nervous system from endogenous or exogenous cellular sources. The brain continues to produce new cells throughout life, and these appear to be capable of taking on normal functions. Moreover, injury of several types, including ischemia, increases the production of new brain cells, which migrate to sites of involvement and may integrate into surviving tissue. This suggests that to at least some extent, the brain is programmed to repair itself through cell replacement. In this session, Harley Kornblum describes the basic biology of neural stem cells and Michael Chopp illustrates how these cells may function in stroke.
But what if the nervous system cannot be stimulated adequately to achieve repair from within? In that case, it is encouraging that neural precursor cells, generated either from embryonic stem cells or partially differentiated cells of neuronal lineage, can be transplanted into the brain and survive, as reported by Gary Steinberg. These cells, too, home to sites of pathology, and may integrate into the host brain. However, as is also true of endogenous neurogenesis, their capacity to restore function to the damaged brain is uncertain.
Studies on neuronal replacement in the normal brain, in stroke, and in other disorders have revealed a large number of growth factors and drugs that can stimulate neurogenesis, but how their effects differ (for example, whether they act on different target cell populations or at different stages of neuronal maturation) has received less attention. Factors like environmental enrichment and learning also influence neurogenesis, and it may be possible to harness these effects in stroke therapy.
One of the problems that hinders clinically relevant basic research on adult neurogenesis is that laboratory investigators are often unaware of the long-term natural history of stroke and the most pressing needs of chronic stroke patients. In this session, Bruce Dobkin addresses questions regarding the time course over which patients typically improve after stroke and the reparative strategies that might make sense in this context. Randolph Nudo describes studies on nonhuman primates that shed light on mechanisms that could account for poststroke recovery, and which prompt consideration of whether new neurons or new pathways are the most apt anatomical substrates for reconstructing the injured brain.
- Accepted December 15, 2006.