Transplantation Of Neural Tissue Research Articles

Circadian rhythmicity after neural transplant to hamster third ventricle: specificity of suprachiasmatic nuclei

Neural transplants into the third ventricle were utilized to quantitatively assess the effectiveness of fetal tissue from selected brain sites in restoring circadian locomotor rhythmicity of adult hamsters rendered arrhythmic by lesions of the suprachiasmatic nuclei (SCN). Circadian function was continuously monitored in recording wheel cages under controlled environmental conditions. Animals which remained arrhythmic for 3–4 weeks after SCN lesions received transplants of neural tissue from 13–14-day-old fetuses: either SCN tissue or non-SCN tissue (cerebral cortex or hypothalamus excluding SCN). Quantitative evaluation of the data indicated partial restoration of circadian rhythmicity in 37% of 19 animals with SCN transplants, but in 0% of the 9 animals with non-SCN neural transplants. The mean time for reappearance of rhythmicity was 20 days after SCN transplantation. Animals were sacrificed 8–10 weeks after transplantation for histological analysis in order to visualize lesion placement and to characterize transplants. The cytoarchitecture and neuropeptide organization of the transplants were consistent with the donor brain region. Only SCN transplants were characterized by aggregates of small neurons with codistributed immunoreactivity for SCN-characteristic neuropeptides.

Microscopic study of fetal hypothalamic tissue transplanted into the third ventricle of senescent female rats

As the female rat ages, her ovarian cycles become irregular and she ceases to ovulate. This aging process of reproductive function appears to be partially due to a neurodegenerative process in the hypothalamic areas responsible for the control of the anterior pituitary gland. There has been some success in recovery of function after transplantation of neural tissue in some cases of genetic neural deficits or in deficits due to lesions of the hypothalamus. This experiment was conducted to determine whether the senescent female rat will regain her ability to ovulate after fetal hypothalamic transplants. Here we describe the morphological development of the hypothalamic transplants.Basal hypothalamic or cortical (control) tissue from fetal rats at 17E were transplanted into senescent Sprague-Dawley female rats demonstrating the cessation of ovulation. Fetal tissue was mechanically dissociated and placed in artificial CSF. Ten μI aliquots of the transplant preparation were infused into the third ventricle of 6 experimental and 6 control animals with a 26 ga Hamilton syringe at a rate of 1 μl/min. The needle remained in place for 5 additional min before it was removed. Animals were monitored for vaginal cyclicity for 30 days. Cyclicity was partially restored in animals transplanted with hypothalamic but not cortical tissue.

Vascularization of fetal cell suspension grafts in the excitotoxically lesioned adult rat thalamus

Several studies have considered the establishment of vascularization in intracerebral solid transplants of neural tissue. The widely supported interpretation of the results is that the vascular network of the solid grafts is already present before implantation into the host brain. The situation is different when dissociated fetal tissue is transplanted as a cell suspension because in these conditions the fetal vascular network is disrupted. The present study has, therefore, been undertaken to follow the angiogenesis in a transplant of dissociated fetal cells implanted into the excitotoxically neuron-depleted thalamus. The vascular network is compared to that observed in the intact and in the lesioned thalamus both in terms of morphology of the capillaries and of the function of the blood-brain barrier (BBB). In the transplant, capillaries, stained by Indian ink, are very few in number and have very fine calibers during the first 20 days after grafting. Some structures can be identified as immature blood vessels at the electron microscopic level. The blood vessels are progressively more numerous in the graft and they demonstrate mature ultrastructural features 2 months after grafting. Last, there is no leakage of the BBB for peroxidase. The vascularization seems to follow a pattern of maturation comparable to that described during development in the literature. In contrast, in the lesioned area, there is a reactive angiogenesis: 10 days after the excitotoxic injection (shortest time studied), there are many wide caliber vessels with expanded perivascular spaces engorged with mesodermal cells. A microvascularization also develops transiently during the first two months. Capillaries are abnormal from the functional point of view, since there is a leakage of the BBB to macromolecules. The use of an experimental model in which transplant had to grow in a lesioned area permits to determine two types of vascularization: an apparently normal developmental timetable, normal morphological and functional characteristics, in the transplant; a reactive angiogenesis, in the lesioned area.

Nerve growth factor (NGF)-treated nitrocellulose enhances and directs the regeneration of adult rat dorsal root axons through intraspinal neural tissue transplants

Severed adult rat dorsal roots were apposed to an intraspinal transplant of fetal spinal cord (FSC) tissue co-grafted with nerve growth factor (NGF)-treated nitrocellulose strips. Axonal regrowth from the injured roots was assessed by calcitonin gene-related peptide immunoreactivity (CGRP-IR). Dense fascicles of regenerating CGRP-IR axons lined the entire length of NGF-treated nitrocellulose, with many crossing the graft host interface ventrally to extend into the host neuropil. In contrast, CGRP-IR axon regrowth was not promoted by untreated nitrocellulose implants. These results indicate that substrate bound NGF can promote and direct the intraspinal regeneration of a specific population of dorsal root axons.

Implantation of Tissue Into the Brain

The transplantation of neural tissue into the brain has the potential to repair the effects of trauma and of congenital abnormalities and to replace tissue that has ceased to function as the result of disease. The brain is not an immunologically privileged site in the strict sense; under certain carefully defined circumstances, grafts can last for long periods of time, but many such grafts are rejected naturally or following various types of provocation. Factors important to the survival of neural grafts are the use of embryonic tissue, the immunogenetic match, the level of expression of major histocompatibility complex antigens in brain cells close to the graft, and the presence of neural degeneration near the graft. Much additional basic experimental work must be done, however, before a rational approach to the clinical use of neural grafts can be undertaken.

Spinal traumas: Some postoperative complications in experimental animals

Animals with severe spinal traumas show paraplegic syndrome and various somatic and autonomie dysfunctions. Of the various dysfunctions those related to hypothermia, bladder problems, and autophagia are of serious nature. The condition of animals with these complications deteriorates rapidly, and the animals are sacrificed for histological and pathological analyses. The findings show that the postoperative complications are related to the degree of severity of the trauma, and that 50–80% animals are lost due to these complications. Most of these animals are lost during the first two weeks after the surgery, and the remaining at later stages. Transplantation of neural tissue at the site of lesion does not ameliorate these postoperative complications and improve the survival rate of the animals.

Use of implantable pumps for central nervous system drug infusions to treat neurological disease.

Increasing knowledge of the neurochemical aspects of central nervous system function raises the possibility of treating neurological disease by the appropriate manipulation of neurotransmitters, neuromodulators, and neurohormones. Clinical application of this knowledge has been inhibited, however, by long-standing problems with drug delivery to the central nervous system (CNS). The availability of implantable drug infusion pumps and stereotactic catheter placement techniques may overcome many of these problems. The problems of drug delivery to the brain and the present and potential uses of implantable drug pumps for neurological disease are discussed. In addition, the relationship between CNS drug infusion and neural tissue transplantation is briefly reviewed.

Pharmacologic consequences of the vascular permeability of chromaffin cell transplants in CNS pain modulatory regions

The transplantation of peripheral neural tissue into the CNS has been shown to alter blood-brain barrier (BBB) permeability to intravascularly injected proteins such as horseradish peroxidase. The pharmacological consequences of such BBB alterations following the transplantation of adrenal medullary tissue, isolated bovine chromaffin cell suspensions, or PC12 cell suspensions into the pain modulatory regions of the periaqueductal gray (PAG) or subarachnoid space of the lumbar spinal cord were studied using agents that normally do or do not readily pass the BBB. The injection of nicotine in animals with adrenal medullary or chromaffin cell transplants produces potent analgesia, most likely due to the stimulated release of opioid peptides and catecholamines from the transplanted cells. This analgesia could be blocked by nicotinic antagonist mecamylamine, which normally passes the BBB, but not by nicotinic antagonist hexamethonium, which normally does not readily pass the BBB. Furthermore, quaternary nicotinic agonists tetramethylammonium and 1,1-dimethyl-phenyl-piperazinium had no effect on pain sensitivity in animals with adrenal medullary implants. The Met-enkephalin peptide analog, d-Ala-Met-enkephalinamide, which normally does not alter pain sensitivity when injected systemically due to limited penetration to the CNS, produced analgesia in animals with adrenal medullary, bovine chromaffin cell, and PC12 cell implants in the PAG, but not in control gelfoam-implanted animals. This analgesia, as well as analgesia induced by nicotine, was completely blocked by naloxone pretreatment, but not by naloxone methobromide, a quaternary derivative of naloxone that does not normally pass the BBB. Results of this study indicate that while CNS permeability to peptides and proteins is altered by peripheral neural transplants, CNS exclusion of highly charged molecules may be intact. The vasculature of such transplants may retain some characteristics of both the in situ peripheral graft tissues and the host CNS.

Transplantation of neural tissue in polymer capsules

Neural tissue reaction to permselective polymer capsules and the feasibility of encapsulated neural tissue transplantation were evaluated in a rat model for a period of 1–12 weeks. Polymer implants in the central nervous system were generally well tolerated. The brain reaction to the synthetic material was minimal and did not disturb normal brain architectonics. Embryonic mouse mesencephalon enclosed in a polymer capsule remained morphologically intact for at least 12 weeks in the parietal cortex of rats. We conclude that the immunoprotection provided by a permselective polymer membrane encapsulating neural tissue is compatible with diffusional exchange of nutrients and metabolites. Polymer encapsulation may provide an alternative for the problem of immunorejection in transplantation of neural tissues.

Neural tissue transplantation. Comments on its role in general neuroscience and its potential as a therapeutic approach.

Neural tissue transplantation. Comments on its role in general neuroscience and its potential as a therapeutic approach.

Embryonic hippocampal grafts ameliorate the deficit in DRL acquisition produced by hippocampectomy

Transplants of fetal neural tissue survive and develop in lesion cavities produced in adult rats. The present experiment tested the effect of grafting fetal hippocampal or brainstem tissue on the ability of rats with hippocampal lesions to perform on a differential reinforcement of low response rate (DRL) operant schedule. The DRL interval was 20 s. Eighty-six percent of the hippocampal grafts and 69% of the brainstem grafts developed to maturity. Inspection of sections stained using a silver technique for axis cylinders or taken from rats in which the mature transplant had been injected with Fast blue, indicated that these grafts formed connections with the host brain. Consistent with previous reports, rats with hippocampal lesions were impaired in performance of the DRL task. Rats given fetal grafts of hippocampal tissue into the hippocampal lesion site on the day of lesion production were significantly better in performance of the DRL requirement than were lesion-only rats or rats receiving grafts of fetal brainstem tissue. The results of this study confirm that grafts of fetal brain tissue can both develop in a lesion site in an adult brain and ameliorate lesion-induced behavioral deficits.

Transplantation of Neural Tissue from Fetuses

Transplantation of Neural Tissue from Fetuses

Transplantation of Neural Tissue from Fetuses

Transplantation of Neural Tissue from Fetuses

Transplantation of neural tissue from fetuses

Transplantation of neural tissue from fetuses

Transplantation of Neural Tissue from Fetuses

Transplantation of Neural Tissue from Fetuses

Cell line segregation during peripheral nervous system ontogeny.

The peripheral nervous system of vertebrates arises from the neural crest and the ectodermal placodes. Construction of quail-chick chimaeras has provided significant information on the migration and fate of the neural crest and placodal cells. Transplantation of neural crest tissue to various sites in these chimaeras has demonstrated that the differentiation of neural crest cells is controlled by environmental influences during their migration and, particularly, during gangliogenesis. Experiments with in vitro and monoclonal antibody techniques have shown that these environmental cues act on a heterogeneous population of neural crest cells whose developmental potencies are partly restricted to definite differentiation pathways.

Neural tissue transplants rescue axotomized rubrospinal cells from retrograde death

Rubrospinal tract cells undergo massive retrograde degeneration following spinal cord damage in newborn rats (Prendergast and Stelzner, J. Comp. Neurol. 166:163-172, '76b). In the current study, fetal spinal cord tissue (E12-14) was grafted into midthoracic spinal cord lesions in newborn rats (less than 72 hours old) in order to determine whether such transplants could modify the response of the immature host central nervous system (CNS) to axotomy. These transplants grew, differentiated, and formed extensive areas of apposition with the recipient spinal cords. Counts of red nucleus (RN) neurons indicated a significant loss of RN neurons in animals with lesion alone, but a rescuing of most of these cells if a transplant was placed into the lesion site. In fact, the number of neurons in animals with lesions and transplants was not significantly different from control animals. Horseradish peroxidase injected 10-15 mm caudal to the transplant (at 1-12 months post-transplantation) labeled neurons within the transplant and RN neurons contralateral to the spinal cord lesions and transplant. In animals with spinal cord lesion but no transplant, only the unaxotomized RN was labeled. Thus, spinal cord transplants prevented the massive retrograde cell death of immature axotomized rubrospinal neurons. Some of these rescued neurons projected to the host spinal cord caudal to the transplant.

Neural Tissue Transplantation Research. Proceedings in Life Sciences Series.

Neural Tissue Transplantation Research. Proceedings in Life Sciences Series.

Hippocampal deafferentation: transplant-derived reinnervation and functional recovery.

A brief review of the capacity of neural tissue transplants to reinnervate the deafferented hippocampus and repair functional deficits induced by the lesion. The techniques for transplantation of solid pieces of embryonic septum, locus coeruleus or raphe nuclei, or tissue suspensions of embryonic septum, to the adult rat hippocampus are described. Such grafts manifest good long-term survival, provide a good reinnervation of the hippocampus that is histochemically and biochemically appropriate and specific, can establish ultrastructural synaptic contacts with the host, and are electrophysiologically active. Rats with septal grafts manifest recovery of the capacity to learn certain aspects of radial 8-arm maze. T-maze alternation and Morris water-maze tasks. Rats with locus coeruleus grafts manifest an amelioration of lesion-induced hyperactivity. It is concluded that neural tissue transplantation provides a powerful new tool in the study of the functional organization of the hippocampus and its various neurotransmitter-specific afferent systems.

Hippocampal deafferentation: transplant-derived reinnervation and functional recovery.

A brief review is provided of the capacity of neural tissue transplants to reinnervate the deafferented hippocampus and repair functional deficits induced by the lesion. The techniques for transplantation of solid pieces of embryonic septum, locus coeruleus or raphe nuclei, or tissue suspensions of embryonic septum, to the adult rat hippocampus are described. Such grafts manifest good long‐term survival, provide a good reinnervation of the hippocampus that is histochemically and biochemically appropriate and specific, can establish ultrastructural synaptic contacts with the host, and are electrophysiologically active. Rats with septal grafts manifest recovery of the capacity to learn certain aspects of radial 8‐arm maze, T‐maze alternation and Morris water‐maze tasks. Rats with locus coeruleus grafts manifest an amelioration of lesion‐induced hyperactivity. It is concluded that neural tissue transplantation provides a powerful new tool in the study of the functional organization of the hippocampus and its various neurotransmitter‐specific afferent systems.