Brain zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Research Bu&rin, Vol. 25, pp. 889-894. o Pergamon Press plc, 1990. Printed in the U.S.A. 0361-9230/90 $3.00 + .OO Tyrosine Hydroxylase-Positive Fibers and Neurons in Transplanted Striatal Tissue in Rats With Quinolinic Acid Lesions of the Striatum PAUL R. SANBERG,’ EVE ZUBRYCKI, MICHAEL E. RAGOZZINO, MAGDA GIORDANO AND MICHAEL T. SHIPLEY Divisions of Neuroscience and Neurobiology Departments of Psychiatry, Anatomy, Psychology, Neurosurgery and Physiology University of Cincinnati College of Medicine, Cincinnati, OH 45267-0559 and Cellular Transplants, Inc., Four Richmond Square, Providence, RI 02904 Received 27 August 1990 SANBERG, P. R., E. ZUBRYCKI, M. E. RAGOZZINO, M. GIORDANO AND M. T. SHIPLEY. Tyrosine hydroxyluse-posirive fibers and neurons in transplanted sniaral tissue in rats with quinolinic acid lesions of the striarum. BRAIN RBS BULL 25(6) 889- 894, 1990. -Using the quinolinic acid (QA) animal model of Huntington’s disease (I-ID) the dopaminergic afferent input to intra- striatal striatal grafts was examined. After bilateral striatal lesions with QA (15 nmol), 4 pl of fetal (E17) striatal tissue were delivered into the lesioned striata. Twenty-eight weeks posttransplantation the tissue was processed for TH immunocytochemistry and cresyl violet staining. In addition fetal intact brains (E17) were also processed for TH immunocytochemistry and cresyl violet staining. Viable striatal grafts were located within the host striatum and in some cases within the lateral ventricles. TH-positive fi- bers were present within the graft and also groups of TH-positive cell bodies were seen in some of the grafts. TH immunocytochem- istry on El7 fetuses revealed several groups of TH-positive neurons one of which was placed immediately ventral to the developing striatal ridge. The origin of TH-positive innervation within the graft is discussed. Tyrosine hydroxylase Striatum Neural transplants Quinolinic acid RECENT studies using an animal model of Huntington’s disease (HD) have shown remarkable behavioral and neurochemical re- covery following the transplantation of fetal neural tissue at the site of injury (4,6). The mechanism which accounts for this re- covery has yet to be elucidated. One theory suggests that anatom- ical connectivity between the graft and host reestablishes the damaged neural circuitry and effectively reinnervates the host brain (2,4). Examination of the morphology of striatal transplants have found that both output and intemeuronal types (spiny and aspiny) are present in the graft (10). Thus, the necessary neuronal components for graft/host connectivity are present under some conditions. The present experiment used tyrosine hydroxylase (TH) im- munocytochemistry as a marker for catecholaminergic activity in animals that had been previously lesioned with quinolinic acid [QA; (1,16)] and transplanted [preliminarily presented elsewhere, (20)]. We were interested in examining the effectiveness of this technique in detecting possible dopaminergic afferent inputs to long-term fetal striatal grafts. The technique was also applied to El7 fetal brains, which were the source of the grafted tissue. METHOD Six Sprague-Dawley rats (250-350 g) were housed individu- ally, given food and water ad lib and kept on a twelve-hour light/ dark schedule (6:00-l&00 h). Rats were lesioned with bilateral injections of quinolinic acid in the striatum. The stereotaxic co- ordinates that were used corresponded to + 1.3 mm anterior to bregma, 2.6 mm lateral to the midline bilaterally, and - 5.2 mm ventral to the dura mater. The animals were anesthetized with an IP injection of sodium pentobarbital (45 mg/kg). One hundred and fifty nmol of QA, pH 7.4 in a volume of 1 pl of saline was injected into each striatum over five minutes as described else- where (15). Thirty days following this procedure rats were again anesthetized and positioned on a Kopf stereotaxic to prepare for ‘Requests for reprints should be addressed to Dr. Paul R. Sanberg, Cellular Transplants, Inc., Four Richmond Square, Providence, RI 02906. 889