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INVESTIGATOR PROFILES |
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SENIOR CONSULTANT ADJUNCT PROFESSOR ADJUNCT PROFESSOR Department of Biology, CONTACT |
Harold K. Kimelberg, Ph.D.Research FocusDr. Kimelberg’s research interests center on the role of astroglia or astrocytes. These cells are numerous cells in the brain which coexist with the better studied neurons, and are so named because most have a star-shaped appearance under the microscope. One important aspect of his research is whether malfunctions of these cells contribute to the early damage in stroke and traumatic brain injury and thus are potential targets for therapy. He and his group have explored the use of blockers of the excessive release of an excitatory chemical messenger in the brain, glutamic acid, which is normally released from neurons in a controlled manner for communication between these cells and then is taken up by the astrocytes to stop further activity. Astrocytes are at least as numerous as neurons and closely surround blood vessels in the brain, and Dr. Kimelberg is recognized as a pioneer researcher in probing their functions. Many of their properties are similar to those seen in neurons , such as they have receptors for various brain chemical transmitters, so it is a challenge to sort out which of the brain’s functions are due to neurons and which to astrocytes, but they unequivocally distinguished by the neurons being excitable (i.e. able to fire action potentials) while the astrocytes are not. However, there are many questions still unresolved on the scope of their functions and whether they form a heterogeneous population. Astrocytes rapidly swell in a number of pathological states affecting the mammalian CNS. The recent discovery that most of the water channels or aquaporins (for whose discovery the Nobel Prize for chemistry was awarded in 2003) in the brain are to be found in astrocytes adds further interest to and tools for studying astrocytic swelling. This swelling is the main underlying condition of cytotoxic or cellular edema, and the consequences of such swelling is therefore of clinical interest. Such consequences include pathological release of the transmitters glutamate which is deleterious when released in excess. Identification of the route of this release will clearly be important. Cellular brain edema is an early event in cerebral trauma and ischemia and is observed within the earliest measured times of 1 to 2 hours after stroke onset in humans by diffusion-weighted MR imaging. Dr. Kimelberg found some 25 years ago, that anion transport inhibitors inhibit such swelling occurring 40 minutes after trauma-hypoxia head injury in cats and also significantly improved neurological recovery and decreased mortality when injected either intravenously or directly into the CNS via the cisterna magna. The same inhibitors also reduced infarct size in a rabbit ischemia model. A compound used clinically for breast cancer, tamoxifen, also inhibits release of glutamate from swollen astrocytes and is a very effective neuro-protectant in rat ischemic models. It would be useful to test tamoxifen clinically as there are presently no neuroprotectants approved for use in stroke and head injury. Dr. Kimelberg has authored or been a co-author of around 250 reviews and experimental papers, has served on the editorial boards of numerous journals, reviews grants for NIH and other national and international agencies, and has presented his work in invited seminars and as a speaker at meetings both here and abroad. He has been the recipient of a Fulbright senior Professorship to study at the University of Heidelberg in 1988. He has graduated six Ph.D. and two master’s students. Selected References (View)
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