Ronald E. Kalil
- Professor, Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health
- (608) 262-4903
Ph.D. Massachusetts Institute Of Technology
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 most often 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. A possible approach to achieve this goal involves transplanting neural stem cells to the injured brain, and then coaxing them to differentiate into new, functionally appropriate neurons and glial cells. Currently, we are transplanting human neural stem cells to the normal and injured adult rat brain to determine whether the transplanted cells differentiate appropriately and integrate with the host brain.
In the hippocampus of every mammalian species that has been studied, including humans, new neurons are produced daily. We are studying hippocampal neurogenesis in normal adult rats to determine the rate of new neuron production and the survival of newly generated neurons. This research is a first step in exploring whether administering a trio of chemotherapeutic drugs commonly used in treating breast cancer interferes with the generation or survival of new neurons in the hippocampus. If so, the work may shed light on a debilitating side effect of chemotherapy, cognitive dysfunction, commonly known as "chemobrain."
In parallel with these two lines of research, we have discovered neural cells in several areas of the adult rat and human brain that the common wisdom would argue should not exist at any stage of neural development or maturation. These unique cells express the cytoskeletal protein nestin, heretofore associated only with neural stem cells, as well as proteins expressed exclusively by mature neurons. The co-expression of nestin and markers of mature neurons suggests that these cells, which we have named nestin neurons, may have stem cell-like properties, and we now are characterizing nestin neurons to determine if they are capable of functioning as endogenous neural stem cells in plasticity-related behavior.
Above image: "Many cell cultures from the cholinergic basal forebrain of the adult rat express nesting (yellow)."
- Ling, C., M.L. Hendrickson and R.E. Kalil. 2012 Resolving the detailed structure of cortical and thalamic neurons in the adult rat brain with refined biotinylated dextran amine labeling. PLoS ONE 7(11): e45886. doi:10.1371/journal.pone.0045886
- Ling, C., M.L. Hendrickson and R.E. Kalil. 2012a Morphology, classification and description of the projection neurons in the dorsal lateral geniculate nucleus of the rat. PLoS ONE 7(11): e49161.doi:10.1371/journal.pone.0049161.
- Hendrickson, M.L., C. Ling, and R.E. Kalil. 2012 Degeneration of axotomized projection neurons in the rat LGN: Temporal progression of events and their mitigation by a single administration of FGF2. PLoS ONE 7(11): e46918. doi:10.1371/journal.pone.0046918
- Hendrickson ML, Rao AJ, Demerdash ONA, Kalil RE, 2011 Expression of Nestin by Neural Cells in the Adult Rat and Human Brain. PLoS ONE 6(4): e18535. doi:10.1371/journal.pone.0018535
- Smith DO, Rosenheimer JL, Kalil RE, 2008 Delayed Rectifier and A-Type Potassium Channels Associated with Kv 2.1 and Kv 4.3 Expression in Embryonic Rat Neural Progenitor Cells. PLoS ONE 3(2): e1604. doi:10.1371/journal.pone.0001604
- Wyatt Potter, R.E. Kalil, and Weiyuan J. Kao. 2008. Biomimetic material systems for neural progenitor cell-based therapy. Frontiers in Bioscience, 13: 806-821.
- Kalil, R.E., Slawson, A. and S.Vermilyea. 2012. Monitoring hippocampal neurogenesis in the adult rat with three thymidine analogs, BrdU, CldU and IdU. Soc. Neurosci.Abstr. Vol. 38.
- Kalil, R.E., S.C. Vermilyea and M.J. Hansen. 2011. Proliferating cells in the subgranular zone of the dentate gyrus in the adult rat continue to divide for at least 14 days after their first division. Soc. Neurosci. Abstr. Vol. 37.
- Hansen, M.J. and Kalil, R.E. (2010) The generation and survival of new granule cell neurons in the hippocampus of the adult rat. Soc. Neurosci. Abstr. Vol. 36.
- Wield, A. and Kalil, R.E. (2009) Nestin expressing cells in the ependymal cell layer of the third ventricle in the adult rat. Soc. Neurosci. Abstr. Vol. 35.
- Hendrickson, M.L. and Kalil, R.E. (2008) A new class of nestin-expressing cells in the adult rat brain. Soc. Neurosci. Abstr., Vol. 34.
- Nguyen, W.T., Buhalog, A., Hendrickson, M and Kalil, R.E. (2007) On the survival of nestin-expressing neurons in the cholinergic basal forebrain after an immunolesion with 192-IgG-saporin. Soc. Neurosci. Abstr., Vol 33.
- Nguyen, W. T., Palecek, E.J., Hendrickson, M.L., Spirio, L.N., and Kalil, R.E. (2006) Encapsulation of neural progenitor cells in a self-assembling, nanofiber peptide hydrogel for transplantation to the injured adult rat brain. Soc. Neurosci. Abstr., Vol. 32.