| Research Summary |
Neural Stem Cells, Adult Neurogenesis and the Injured Brain
When the brain is damaged, injured neurons die and typically are not replaced. This cell death frequently results in a loss of function by the affected region of the brain. However, if neurons that have died could be replaced and their connections rebuilt, normal function might be restored. There are two possible approaches available to achieve this goal. One involves transplanting neural stem cells to the injured brain, and then coaxing them to differentiate into new, functionally appropriate neurons and glial cells. The second approach acknowledges that new neurons are produced in the brain throughout life, and endeavors to encourage these newly generated neurons to replace those that have died. We are investigating both of these approaches.
In previous work, we have shown that embryonic neural stem cells transplanted to the injured adult brain will survive and differentiate into neurons and glial cells. Currently, we are studying methods to enhance the survival and intergration of transplanted cells. In parallel with this research, we have discovered that cells in several areas of the adult brain express the cytoskeletal protien nestin. This suggests that these cells may be neural stem cells or have stem cell-like properties. We now are characterizing these nestin-positive cells in detail as a first step in determining whether they may be capable of funtioning as endogenous neural stem cells.
The research underway is conducted in vitro and in vivo, and spans molecular neurobiology to systems neuroscience. However, all of it converges on a common goal; to restore behavioral function that has been compromised or lost because of brain injury by replacing cells that have died an rebuilding appropriate neural connections. |
| Representative Publications |
Rao, A.J. M.L. Hendrickson, S. Salamat, and Kalil, R.E. 2005. Nestin expression by terminally differentiated neurons in the adult human brain. Soc. Neurosci. Abstr., Vol. 31.
Hendrickson, M.L., A.J. Rao, and Kalil, R.E. 2005. Nestin Expression by neurons in the dorsal neocortex of the early postnatal rat brain. Soc. Neurosci. Abstr., Vol. 31.
Smith, D.O., Kalil, R.E., and J.L. Rosenheimer. 2005. Voltage-gated potassium channel expression in embryonic rat neural progenitor cells. Soc. Neurosci. Abstr., Vol. 31.
Rao, A.J. Demerdash, O.N., Hendrickson, M.L. and Kalil, R.E. (2004) Nestin expression by terminally differentiated neurons in the adult brain. Soc. Neurosci. Abstr., Vol. 30, available online here.
Smith, D.O. and Kalil, R.E. (2004) Electrical properties of embryonic rat neural stem cells. Soc. Neurosci. Abstr., Vol. 30, available online here.
Hendrickson, M. L. and Kalil, R.E. (2003) Labeling of neural progenitor cells transplanted to the adult brain with CFDA, SE. Soc. Neurosci. Abstr., Vol. 29, available online here.
Demerdash, O. and Kalil, R.E. (2003) Development of nestin expression in the brain of the rat. Soc. Neurosci. Abstr. Vol. 29.
Demerdash, O., Paulus, J. and Kalil, R.E. (2002} Widespread expression of nestin by cells in the adult brain. Soc. Neurosci Abstr., Vol. 28, available online here.
Stein, T., J. Fedynyshyn, and Kalil, R.E. 2002. Circulating autoantibodies recognize and bind dying neurons following injury to the brain. J. Neuropath and Exp. Neurol., 61: 1100-1108.
Kalil, R.E. and Gopal, P. P. (2001) Newly differentiated neurons in the adult rat brain after injury to the visual cortex. Soc. Neurosci. Abstr., Vol. 27.
Ling, C., Learish, R., Bruss, M., Haak-Frendscho, M. and Kalil, R.E. (2000) Survival and differentiation of neural progenitor cells transplanted into the brain of adult rats immediately following a lesion of visual cortex. Am. Soc. Neurochem. Vol.74 (suppl), S-75D.
Agarwala, S. and Kalil, R.E. 1998. Axotomy-induced neuronal death and reactive astrogliosis in the lateral geniculate nucleus following a lesion of visual cortex in the rat. J. Comp. Neurol. 392: 252-263.
Agarwala, S. and Kalil, R.E. 1998. Long-term protection of axotomized neurons in the dorsal lateral geniculate nucleus in the rat following a single administration of basic fibroblast growth factor or ciliary neurotrophic factor. J. Comp. Neurol. 392: 264-272.
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