We have shown that pain sensitivity can be reduced by transplanting adrenal medullary tissue or isolated chromaffin cells into such CNS pain modulatory regions in the rat at the midbrain periaqueductal gray (PAG) or extra- parenchymally in the subarachnoid space of the dorsal lumbar spinal cord. We have obtained promising results in preliminary clinical studies using allografts of adrenal medulla to relieve cancer pain. In addition to allografts, we have found that bovine chromaffin cells survive well in the rat CNS. Xenografts are a potentially important untapped donor source that may overcome the limited availability of human donors. The stability of the transplants and host-graft integration, and conditions necessary for continued graft maintenance, are critical and will be addressed.
Intermediate Filament Markers for Human Astrocytes
The developmentally-expressed structural (IF) and associated (IFAP) proteins of the intermediate filament cytoskeleton comprise a rich source of potential markers. Markers which constitute the focus of this work are an intermediate filament-associated protein (IFAP-300kD as a potential marker of neoplastic astrocytes. These markers are found during embryonic development but are not found in the normal adult CNS. Other markers that have been used to identify astrocytomas may also be present in reactive astrocytes. Our IFAP-300kD is marker is unique in that it is not present in the normal adult brain. We are further characterizing this protein. Since it can be used in unfixed frozen tissue we are planning to produce alternative antibodies to IFAP 200kD and study its expression in fixed specimens.
Publications:
1. Yang, H.-Y., Lieska, N., Glick, R., Shao, D., and Pappas, G.D., 1993. Expression of intermediate filament-associated protein 300kD distinguishes malignant from normal human astrocytes. Proc. Natl. Acad. Sci. USA. 90:8534-8537.
2. Winnie, A.P., Pappas, G.D., Das Gupta, T.K., Wang, H., Ortega, J.D., Sagen, J., 1993. Subarachnoid by adrenal medullary transplants for terminal cancer pain: A report of preliminary studies. Anesthesiology . Vol. 79, No. 4 644-653.
3. Sagen, J., Ortega, J.D., and Pappas, G.D., 1994. Neuropeptide and catecholamine delivery to the CNS by implanted chromaffin cells. In: Providing Therapeutic Access to the Brain: Alternate Approaches, Methods in Neuroscience, 21:348-368, Flanagan, T.R., Emerich, D.F., and Winn, S.R., eds.
4. Hama, Aldric T., Sagen, J. and Pappas, G.D., 1994. Morphological characterization of dorsal horn spinal neurons in rats with unilateral constriction nerve injury: A preliminary study. Neurological Research , Volume 16, August, 297-304.