Neural Transplants

The story of mammalian neural transplantation really begins eighty-one years ago. In Chicago in December of 1903, a 34-year-old physician, Elizabeth Hopkins Dunn, working as a research assistant in neurology, initiated a series of experiments to examine the ability of neonatal rat cerebral tissue to survive transplantation into the brain of matched littermates. Out of 46 attempts, four clearly successful grafts were identified. The publication of Dunn's results in 1917, the first credible report to demonstrate the feasibility of mammalian CNS transplants, generated little interest. In fact, the next significant experiment in this field did not appear until 1930. The field continued to grow slowly and quietly as investigators gradually realized the value of neural trans­ plantation to study problems of development and plasticity in the mammalian nervous system. With the discovery in 1979 that grafted neurons were capable of appropriate and functional interactions with the host brain, interest in neural transplantation esca­ lated sharply. The extraordinary opportunities created by using functional neural trans­ plants in investigating basic issues in neurobiology, as well as the clinical implications, excited both scientists and the public. The popularity of neural transplantation has been growing rapidly in the past five years and shows no signs of abating. The present volume was designed to meet two needs created by the rapid growth of this subdiscipline of neurobiology. The first was to provide a thorough review of the experimental foundations of neural transplantation.

1 Neural Transplants in Mammals: A Historical Overview.- 1. Introduction.- 2. The First Fifty Years: 1890–1940.- 3. 1941–1970: Sporadic Progress.- 4. Summary of Progress from 1890 to 1970.- 5. 1970–1980: A Quickening Tempo.- 6. Analysis.- References.- 2 Transplantation by Microinjection: Heterospecific Analysis of Avian Neural Crest Migration and Differentiation.- 1. Introduction.- 2. Neural Crest Cell Marking Techniques.- 3. The Injection Technique.- 4. Migration of Embryonic Cells along the Ventral Crest Pathway.- 5. Clonal Analysis of Neural Crest Cell Differentiation.- 6. Latex Beads as Inert Probes of Neural Crest Migration.- 7. Conclusion.- References.- 3 Neural Transplants in Lower Vertebrates.- 1. Introduction.- 1.1. The Organisms.- 1.2. The Transplantations: Definitions.- 1.3. The Neural Structures.- 2. The Fate and Orientation of the Neural Tissues.- 2.1. The Brain.- 2.2. The Retina.- 2.3. The Ear and Limb.- 3. Axonal Outgrowth.- 4. Axonal Navigation.- 4.1. Reaching the Target.- 4.2. Secondary Targets.- 4.3. Direction of Growth.- 4.4. Decussation.- 4.5. Physiological Activity.- 4.6. Common Cues.- 5. The Formation of Specific Connections.- 5.1. Pathways and Fiber Interactions.- 5.2. Timing.- 5.3. Activity.- 5.4. Secondary Selection.- 5.5. Stripes.- 5.6. Induction of Polarity.- 5.7. Other Systems.- 5.8. Peripheral Specification.- 5.9. Ectopic Terminations.- 5.10. Interacting Topographies.- 6. Hypoplasia and Hyperplasia.- 6.1. Changes in Size of Projecting Populations.- 6.2. Changes in Size of Target.- 7. Regeneration.- 7.1. Pathway Selection and the Formation of Connections.- 7.2. Tectal Markers.- 7.3. The Pigment Epithelium.- 7.4. Motoneurons and Foreign Innervation.- 7.5. Transfer of Memory and Behavior.- 8. Discussion.- 9. Summary.- References.- 4 Transplantation of the Developing Mammalian Visual System.- 1. Introduction.- 2. The Transplantation Technique.- 3. General Aspects of Transplant Development in Neonates.- 4. Retinal Transplants.- 4.1. Histological Characteristics.- 4.2. Connections with the Host Brain.- 4.3. Retina Transplanted to Other CNS Locations.- 5. Tectal Transplants.- 5.1. Histological Characteristics.- 5.2. Connections with the Host Brain.- 6. Cortical Transplants.- 6.1. Histological Characteristics.- 6.2. Connections with the Host Brain.- 7. Transplants to Adult Hosts.- 8. Discussion.- 8.1. Differentiation of the Transplants.- 8.2. Specificity of Connections.- 9. The Future for Transplantation Studies.- References.- 5 Camera Bulbi Anterior: New Vistas on a Classical Locus for Neural Tissue Transplantation.- 1. Introduction.- 2. Transplantation Procedure.- 3. Observations through the Cornea.- 4. Nerve Fibers in the Rat Iris.- 5. Electrophysiological Recordings from Intraocular Grafts.- 5.1. Possibilities to Add Drugs.- 5.2. Possibilities to Stimulate Nerves in Intraocular Grafts.- 5.3. Recording from Intraocular Brain Tissue Grafts.- 6. Intraocular Grafts of Peripheral Nervous Tissues.- 6.1. Adrenergic Ganglia.- 6.2. Sensory Ganglia.- 6.3. Auerbach’s Plexus.- 6.4. Adrenal Medulla.- 7. Intraocular Grafts of CNS Tissues.- 7.1. Cerebellar Grafts Maintain Organization and Function.- 7.2. Hippocampal Grafts: Structure and Function, Inputs from Host Iris.- 7.3. Area Dentata Grafts: Intrinsic Organization.- 7.4. Cortex Cerebri Grafts: Tropic Influences of Other Brain Areas during Development.- 7.5. Spinal Cord Grafts: Initial Observations.- 7.6. Caudate Grafts.- 7.7. Central Noradrenaline, Dopamine, and 5-Hydroxytryptamine Neurons Grafted to the Eye Chamber.- 8. General Conclusions.- References.- 6 The Olfactory Organ: Neural Transplantation.- 1. Introduction.- 2. Transplantation in Amphibians.- 3. Transplantation in Mammals.- 3.1. Partial and Total Removal of the Olfactory and Accessory Olfactory Bulb.- 3.2. Embryonic Brain and Olfactory Mucosa Grafts.- 4. Concluding Remarks.- References.- 7 Correction of Genetic Gonadotropic Hormone-Releasing Hormone Deficiency by Preoptic Area Transplants.- 1. Factors Involved in the Regulation of the Hypothalamic—Hypophyseal—Gonadal Axis.- 2. Nature of the hpg Animal and Its Endocrine Status.- 3. Effect of Fetal Preoptic Area Transplants in Male hpg Animals.- 4. Effect of Fetal Preoptic Area Transplants in Female hpg Animals.- 5. Possible Role of Donor Sex in Functioning of CNS Transplants.- 6. Conclusion.- References.- 8 Hypothalamic Grafts and Neuroendocrine Cascade Theories of Aging: Immunocytochemical Viability of Preoptic Hypothalamic Transplants from Fetal to Reproductively Senescent Female Rats.- 1. Introduction.- 2. Methods.- 2.1. Subjects and Experimental Design.- 2.2. Transplant Surgery.- 2.3. LHRH Immunocytochemistry.- 2.4. LH Radioimmunoassay.- 3. Results and Discussion.- 3.1. LHRH Immunocytochemical Viability.- 3.2. Functional Effects of POA Grafts.- References.- 9 Brain Tissue Transplants and Reproductive Function: Implications for the Sexual Differentiation of the Brain.- 1. Introduction.- 2. Transplantation of Male Brain Tissue into Female Recipients.- 2.1. Intraparenchymal Transplants.- 2.2. Transplantation Protocol and Graft Viability.- 2.3. Effects on Masculine Sexual Behavior.- 2.4. Effects on Feminine Sexual Behavior.- 3. Transplant Connectivity with Recipient Brain Tissue.- 4. Hormonal Effects Induced by Transplanted Male Brain Tissue.- 5. Effects of Testosterone Treatment of Recipient on Transplant Volume.- 6. Transplantation of Radioactively Labeled MPOA Tissue Containing the SDN-POA.- 7. Summary.- References.- 10 Morphological and Functional Properties of Transplanted Vasopressin Neurons.- 1. Introduction.- 2. The Hypothalamic Neurosecretory System.- 2.1. Vasopressin.- 2.2. Anatomy.- 3. The Transplantation Procedure.- 4. Anatomical Characteristics.- 4.1. General Features.- 4.2. Vascularization.- 4.3. Peptidergic Neurons.- 4.4. Catecholaminergic Neurons.- 5. Functional Considerations and Discussion.- 5.1. Transplants into Young Adult Hosts.- 5.2. Transplants into Aged Hosts.- 5.3. Transplants into Neurohypophysectomized Rats.- 6. Summary.- References.- 11 The Use of Fetal Hypothalamic Transplants in Developmental Neuroendocrinology.- 1. Introduction.- 2. Differentiation of Embryonic Hypothalamic Transplants.- 2.1. Dopamine Histofluorescence.- 2.2. Neuropeptide Immunocytochemistry.- 2.3. Estradiol Autoradiography.- 2.4. Summary.- 3. The Use of Transplants to Study the Role of Steroid Hormones in Hypothalamic Development.- 3.1. Sexual Differentiation and the Development of Estrogen Receptors.- 3.2. Glucocorticoid Influences on the Differentiation of Magnocellular Neurons.- 4. Neuroendocrine Function of Hypothalamic Transplants.- 5. Summary.- References.- 12 Specificity of Termination Fields Formed in the Developing Hippocampus by Fibers from Transplants.- 1. Introduction.- 2. Normal Organization of the Dentate Gyrus.- 3. Restoration of Septal Lamination by Septal Tissues Transplanted into the Entorhinal/Occipital Cortex.- 4. Absence of Guidance by Degenerative Debris.- 5. Patterns Formed by Serotonin Fibers from Raphe Transplants.- 6. Possible Coexistence of Transmitters in Raphe Transplants.- 7. Comparison between Septal and Striatal Transplants.- 8. Competition between Native and Transplanted Cholinergic Fibers.- 9. Factors Involved in Lamination of Cholinergic Fibers in the Dentate Gyrus.- 10. Possible Basis for Enhanced Survival in the Two-Stage Procedure.- 11. Summary and Conclusion.- References.- 13 Use of CNS Implants to Promote Regeneration of Central Axons across Denervating Lesions in the Adult Rat Brain.- 1. Introduction.- 2. Techniques.- 3. Survival of the Implants.- 4. Regeneration of Central Adrenergic and Cholinergic Axons into the Implants.- 4.1. Transplants of Peripheral Tissues.- 4.2. Hippocampal Transplants.- 5. Bridging of Regenerating Central Cholinergic Axons across Lesions in the Hippocampal Fimbria.- 6. Comments.- References.- 14 Intracephalic Embryonic Transplants: A New Experimental Preparation for Developmental Neurobiology.- 1. Introduction.- 2. Transplant Growth and Survival.- 3. Transplant Organization.- 3.1. Brain Stem Transplants.- 3.2. Hippocampal Transplants.- 3.3. Cerebellar Transplants.- 4. Conclusions.- References.- 15 Transplantation of Newborn Brain Tissue into Adult Kainic-Acid-Lesioned Neostriatum.- 1. Introduction.- 2. Methods.- 3. Results.- 4. Discussion.- References.- 16 Transplantation of Catecholamine-Containing Tissues to Restore the Functional Capacity of the Damaged Nigrostriatal System.- 1. Introduction.- 2. Methods.- 2.1. Terminology.- 2.2. Dissection and Tissue Preparation.- 2.3. Implantation Techniques.- 3. Histology and Catecholamine Production.- 3.1. Substantia Nigra Grafts.- 3.2. Adrenal Medulla Grafts.- 3.3. Comparison of Substantia Nigra and Adrenal Medulla Grafts.- 4. Rotational Behavior.- 4.1. The Rotational Behavior Model and Supersensitivity Phenomena.- 4.2. Embryonic Brain Grafts.- 4.3. Adrenal Medulla Grafts.- 4.4. Other Tissues.- 4.5. The Issue of Controls.- 5. Other Behaviors.- 5.1. Spontaneous Asymmetry.- 5.2. Sensory Neglect.- 5.3. Aphagia and Adipsia.- 5.4. Self-Stimulation.- 6. Electrophysiology.- 7. Future Directions.- 8. Conclusions.- 9. Summary.- References.- 17 Transplantation Strategies in Spinal Cord Regeneration.- 1. Introduction.- 2. Spinal Cord Transplantation Models.- 2.1. Intraspinal Transplants for Axonal Bridging.- 2.2. Extraspinal Transplants for Axonal Bridging.- 2.3. Intraspinal Transplants for Replacing Supraspinal Inputs.- 3. Discussion.- 3.1. Intraspinal Transplants for Axonal Bridging.- 3.2. Extraspinal Transplants for Axonal Bridging.- 3.3. Intraspinal Transplants for Relay Bridging.- 3.4. Intraspinal Transplants for Replacing Missing Supraspinal Inputs.- 4. Concluding Remarks.- References.- 18 Some Consequences of Grafting Autonomic Ganglia to Brain Surfaces.- 1. Introduction.- 1.1. Superior Cervical Ganglion as a Graft.- 1.2. Fourth Ventricle as a Graft Site.- 2. Regeneration in the SCG Graft.- 3. Tropic Effects.- 3.1. Neurotropic Effects.- 3.2. Gliotropic Effects.- 4. Hypothalamic Grafts to the Brain Surface.- 5. Effects on the Blood-Brain Barrier.- 6. Enhanced Survival of Transplanted Autonomic Neurons.- References.