Description
Cell transplantation to the brain and spinal cord is a well-established research tool for studies on cellular and molecular mechanisms, but can it be developed into a useful therapuetic approach in human neurological disorders? Clinical trials in patients with Parkinson’s disease have provided encouraging evidence, however, no treatment based on transplantation is available yet. An overview of current research is given in this book. It summarizes the status of grafting in humans and discusses scientific problems that have to be solved before intracerebral transplantation can become a useful routine approach to treatment. References.- Transplantation in Parkinson’s Disease.- Experimental Studies in Animal Models of Parkinson’s Disease.- 6-OHDA and MPTP Lesion Models.- Grafting of Embryonic Dopamine Neurons.- Human Embryonic Dopamine Neurons Grafted into the Rat Brain.- Grafting of Adrenal Medulla.- Clinical Studies in Patients with Parkinson’s Disease.- Grafting of Adrenal Medulla.- Grafting of Embryonic Dopamine Neurons.- Research Strategies for the Development of a Transplantation Therapy in Parkinson’s Disease.- Adrenal Medulla.- Embryonic Dopamine Neurons.- Other Approaches.- Conclusions.- References.- Transplantation in Huntington’s Disease: Experimental Basis and Clinical Perspectives.- Experimental Model.- Implants of Fetal Striatal Primordia.- Intrinsic Organization of the Striatal Grafts.- Biochemical Markers of Striatal Graft Maturation and Function.- Amelioration of Lesion-Induced Behavioral Deficits.- Mechanisms of Action of the Intrastriatal Grafts.- Afferent Regulation of the Grafted Neurons.- Trophic Effects of Striatal Transplants.- Studies in Primates.- Clinical Perspectives.- References.- Neural Transplantation in Dementia.- Common Terminology in Research on Alzheimer’s Disease.- Models of Cholinergic Deficiency.- Cholinergic Hypothesis.- Cholinergic Grafts in Rats and Monkeys with Lesions.- Cholinergic Grafts in Aging Animals.- Models of Trophic Factor Deficiency.- Role of NGF in Trophic Support.- Transplants as NGF Delivery Systems.- Critical Neuropathology of Alzheimer’s Disease.- Cortical and Subcortical Cell Loss.- Amyloid, Plaques, and Tangles in Dementia.- Graft Models of the Cellular Pathology of Alzheimer’s Disease.- Cellular Pathology in Aging Grafts.- Trisomy 16 Transplant Model.- Future Prospects for Better Functional Animal Models.- Clinical Prospects in Dementia.- References.- Transplantation in Experimental Epilepsy.- Noradrenergic Grafts in Experimental Epilepsy.- Hippocampal Kindling of NE-Depleted Forebrain.- Spontaneous and Picrotoxin-Induced Seizures in Animals with Subcortical Hippocampus Denervation.- Audiogenic Seizures in Genetically Epilepsy-Prone Rats.- Penicillin-Induced Seizures in Fetal Hippocampus Tissue Implanted in the Eye.- Other Grafts in Experimental Epilepsy.- Serotoninergic Neurons.- GABA-ergic Neurons.- Present Lines of Research and Clinical Perspectives.- Norepinephrine-Producing Grafts.- GABA-Producing Grafts.- Concluding Remarks.- References.- Genetically Modified Cells for Intracerebral Transplantation.- Genetically Modified Cells and the Neurotrophic Strategy.- Genetically Modified Cells for Neurotransmitter Replacement.- Discussion and Future Directions.- References.- Immunologic Aspects of Intracerebral CNS Tissue Transplantation.- General Aspects of Transplantation Immunology.- The Brain as a Transplantation Site.- Donor Tissue Properties.- Brain-Derived Antigen-Presenting Cells.- Inflammatory Responses.- Major Histocompatibility Complex Regulation in Grafted Tissue In Situ.- In Situ.- Regional Lymphatic Tissue.- Graft Vascularization and Blood-Brain Barrier Formation.- Lymphocyte Passage Across the Blood-Brain Barrier.- Locally Produced Immunosuppressive Factors.- Immunologic Experiences of Intracerebral Transplantation in Animals.- Prolonged Graft Survival in the Brain.- Immunologic Experience of Intracerebral Transplantation in Patients with Parkinson’s Disease.- Conclusions.- References.
