ANIMAL-MODEL OF HUMAN MEDULLOBLASTOMA - CLINICAL, MAGNETIC-RESONANCE-IMAGING, AND HISTOPATHOLOGICAL FINDINGS AFTER INTRA-CISTERNAL INJECTION OF MHH-MED-1 CELLS INTO NUDE RATS

To establish an animal model of human medulloblastoma, we have injecte d human MHH-MED-1 cells into the cisterna magna of nude rats. Tumors g rew in 3 out of 4 animals injected with 10(6) medulloblastoma cells. A ffected animals showed little or no weight gain and eventually lost we ight but did not develop obvious neurological symptoms until the end o f observation on day 31 after inoculation. At this time, magnetic reso nance imaging (MRI) in tumor-bearing rats revealed contrast enhancemen t in the region of the fourth ventricle and the cisterna magna. Neurop athological examination demonstrated corresponding leptomeningeal grow th in the cisterna magna invading the medulla oblongata and tumor grow th within the fourth ventricle invading the pens. The tumors basically showed the same immunostaining pattern as MHH-MED-1 cells in vitro ex pressing neuron-specific enolase (NSE) and vimentin, but no neurofilam ents (NFE), synapthophysin, or glial fibrillary acidic protein (GFAP). No tumor grew in the fourth animal, which had a normal weight gain an d no alteration on MRI. In conclusion (1) the intrathecally injected h uman medulloblastoma cells spread similar to medulloblastomas in patie nts, (2) tumor growth is readily detected by MRI, (3) the new animal m odel is a suitable tool for further Experimental research including in trathecal therapeutic studies. (C) 1997 Wiley-Liss, Inc.