Transplantation of autologous sympathetic neurons as a potential strategy to restore metabolic functions of the damaged nigrostriatal dopamine nerve terminals in Parkinson's disease.

Grafting of catecholamine-producing cells can be a possible therapeutic strategy for attenuating motor symptoms in Parkinson's disease (PD). The potential of autologous sympathetic neurons has been investigated as a donor for cell therapy of PD. The clinical trials of autotransplantation of sympathetic ganglion cells in PD have revealed that the grafts increase the duration of L-DOPA (L-dihydroxy phenyl alanine)-induced beneficial effects, and that the graft-mediated effect is detectable during a follow-up period of at least 1 year postgrafting. In an in vitro analysis of the ability of human sympathetic neurons to release catecholamines, although DA was not detectable under basal conditions, DA levels were significantly increased upon exposure to exogenous L-DOPA. Furthermore, animal experiments with xenografting of human sympathetic ganglionic neurons in the DA-denervated striatum of rats demonstrated that a significant increase in striatal DA levels is noted after systemic L-DOPA treatment, and that the DA levels remain high for longer periods of time in the grafted rats than in control animals with sham surgery. The L-DOPA-induced rise of striatal DA levels was significantly attenuated when given reserpine pretreatment. This suggests that DA derived from exogenously administered L-DOPA is subjected to, at least in part, vesicular storage in grafted sympathetic neurons. Histological examinations indeed showed that the grafts express aromatic-L-amino acid decarboxylase and vesicular monoamine transporter-2, both of which are important molecules for the synthesis and the storage of DA, respectively. Taken together, grafted sympathetic neurons can provide a site for both the conversion of exogenous L-DOPA to DA and the storage of the synthesized DA in the DA-denervated striatum. This might be an explanation for a mechanism by which sympathetic neuron autografts can increase the duration of L-DOPA effects in PD patients. This review article summarizes the clinical effect of transplantation of autologous sympathetic neurons in PD and discusses the underlying mechanism for the effect based on experimental evidence previously obtained.

Reconstruction of the Sympathetic Chain.

There is a small subset of patients who have undergone endoscopic thoracic sympathectomy for hyperhidrosis or facial blushing who are dissatisfied and would wish reversal. Compensatory sweating is the most common side effect that causes a person to regret surgery. Treatment options are limited and usually not effective in patients with severe side effects from sympathectomy. Nerve graft interposition has been proven to be effective in experimental models and small clinical series. Da Vinci robotic nerve graft reconstruction with interposition graft and direct suturing of nerve and high magnification dissection most closely mirrors standard nerve reconstruction principles when done as a minimally invasive procedure.

Alterations of the blood-brain barrier after transplantation of autonomic ganglia into the mammalian central nervous system.

Autonomic (superior cervical) ganglia, the vessels of which are freely permeable to macromolecules, from mature rat donors (allografts or autografts) were transplanted to different sites in the central nervous system (CNS). Minimal trauma was caused by grafts into the IVth ventricle while grafts to intraparenchymal locations such as cerebral cortex and spinal cord were necessarily traumatic and produced glial scarring. Postoperative periods were between 4 weeks and 30 months. A potentially significant aspect of neural transplantation is the functional vascular connections between host and graft. It is highly likely that grafting procedures alter the blood-brain barrier (BBB) in the recipient brain. In order to determine permanent BBB changes, the glycoprotein horseradish peroxidase (HRP) (M.W. 40,000) was injected intravascularly for circulation periods ranging between 50 seconds and 90 minutes. Protein exudation was monitored by using the chromogens DAB and the highly sensitive TMB. All autonomic ganglia transplants, regardless of postoperative or HRP circulation times, were permeable to the injected protein; no qualitative differences were found between allografts and autografts. The blood-borne protein traversed the autonomic graft and infiltrated into the host brain for distances between 200 micron in intraparenchymal grafts to over 1 mm in intraventricular grafts; a smaller exudate was found in the intraparenchymal model than in the intraventricular site probably due to glial scarring that impeded the protein movement in the interstitial spaces. Significantly, TMB demonstrated that the systemic protein entered the cerebrospinal fluid. HRP was detected on the ventricular floor and in the perivascular spaces of the microvasculature. Transplantation of an autonomic ganglion into the brain provides a biological portal that bypasses normal barriers to macromolecules. The vascular and extracellular confluences between host and graft could provide direct access for systematically administered substances to enter brain regions where they, normally, would be excluded.

Membrane specializations and extracellular material associated with host astrocytes in peripheral neural transplants.

The work of Aguayo and colleagues [Aguayo, David and Bray (1981) J. Exp. Biol. 95, 231-240] demonstrates that grafts of peripheral neural tissue are able to induce regenerative elongation of cut axons in the adult central nervous system. Elucidation of the mechanism of this response requires an understanding of the cellular interactions induced by these types of transplant. In previous studies [Zhou, Lawrence, Morris and Raisman (1986) Neuroscience 17, 815-827; Zhou, Lindsay, Lawrence and Raisman (1986) Neuroscience 17, 803-813] we have transplanted decapsulated adult superior cervical sympathetic ganglia or nodose ganglia into either the septal nuclei or the choroid fissure of adult syngeneic rat hosts. We found that host astrocytes invade the transplants along Schwann cell fascicles and around blood vessels. This raises the questions of what form the migrating astrocytes take, what routes they follow, and what is their fate. In the present study we have taken advantage of the fact that at longer survivals astrocytes accumulate as "paravascular cuffs", and we show that they have several specialized ultrastructural features, such as plasmalemmal caveolae, desmosomes, hemidesmosomes and accumulations of extracellular material. The specific stimuli inducing (or enhancing) these astrocytic specializations and their significance in relation to the wider morphogenetic events induced by peripheral neural transplants remain to be elucidated. However, the observations are further evidence of the remarkable mobility and plasticity of central astrocytes in transplantation situations, and in particular emphasize the involvement of the cell surface and its relationship to extracellular matrix.

Homotransplant of pelvic ganglion into bladder wall in adult rats.

In these experiments a large portion of the pelvic ganglion of adult female rats was transplanted into the wall of the urinary bladder of the same animals. The morphology and fine structure of the transplants were studied in whole-mounts and in sections for light and electron microscopy, from two days up to four months after operation. The general architecture of the ganglion was preserved in all the transplants. The vascularization was re-established. Nerves grew out of the transplant and connections with the original intramural nerves of the bladder wall were established. All the synapses degenerated at the time of transplantation; new synapses began to reappear on the ganglion neurons in the oldest transplants. Although some neurons in the transplant degenerated during the first few days, the majority of neurons survived for the full length of the experiments (four months). Satellite glial cells and small intensely fluorescent cells had a similar structure and distribution as in control ganglia. The results show that the homotransplant of pelvic neurons into the bladder has a high rate of success, in terms of survival, maintenance of fine structure, growth and re-connections; these neurons of adult organisms display plastic and regenerative abilities.

Migration of host astrocytes into superior cervical sympathetic ganglia autografted into the septal nuclei or choroid fissure of adult rats.

Adult astrocytes and their processes, identified by glial fibrillary acidic protein immunohistochemistry and by electron microscopy, migrate into superior cervical ganglia auto-transplanted into the choroid fissure or septal nuclei of adult rats. Migration routes were along the blood vessels, and along the Schwann cell bundles of the transplant. Ultrastructurally, astrocytic processes could be seen to lie in direct contact with Schwann cell processes within the basal lamina enwrapping the Schwann cell and its associated axons. Around the region of the host/transplant interface, the astrocytes were transformed into flattened cells with many short, irregular, fringe-like processes, but within the depths of the transplant mass they resumed a more stellate configuration. Glial fibrillary acidic protein immunoreactivity was present within the intrinsic satellite and Schwann cells of the grafted ganglia, but at a much lower level than in the host astrocytes. It is concluded that reactive astrocytes from adult host central nervous system migrate into peripheral ganglionic transplants, where they differentiate and establish organized arrangements with the ganglionic elements.

Extent of survival and vascularization of adult superior cervical sympathetic or nodose ganglia transplanted into the septal nuclei or choroid fissure of adult rats.

Adult superior cervical sympathetic ganglia were auto-transplanted, and adult nodose ganglia were homografted into the septal nuclei or the choroid fissure of adult Wistar rats. At times from 4 h to 9 weeks after operation, the distribution of surviving transplanted neurons was compared with the development of the transplant vascularization, as visualized by transcardial Indian ink filling of the host vascular system. Within 24 h, the ganglionic neurons and Schwann cells of the interior of the transplants in both sites were necrotic. The surviving neurons and Schwann cells formed a shell, occupying those areas of the transplant periphery which were in direct contact with the host circulation. Occasional ink-filled vessels were evident at this time in transplants in the choroid fissure, but there were none in the septal nuclei, where vessels did not appear until the next day. Blood vessels reached the centre of the ganglia by 3-4 days in the choroid fissure and one week in the septal nuclei, the finest diameter capillaries forming last. At longer survivals there was a slow loss of neurons, notable between 1 and 2 months, and leading progressively (especially in the septal transplantation site) to the disappearance of all but a very small number of ganglionic neurons. The general findings were similar for both types of ganglion, and in both sites, but the initial cell loss was much greater for both types of ganglia in the septum (over 90%) as compared with about a 50% loss in the choroid fissure. The initial rapid cell loss was probably a result of ischaemia. The subsequent, slow progressive loss may be associated with failure to make or receive neuronal connections, or the absence of appropriate growth factors.

Xenografting human T2 sympathetic ganglion from hyperhidrotic patients provides short-term restoration of catecholaminergic functions in hemiparkinsonian athymic rats.

Previous studies have suggested that allografting peripheral sympathetic ganglia, such as superior cervical ganglia, partially relieves clinical or behavioral deficits in parkinsonian patients and animals. However, removal of these ganglia can cause Homer's syndrome, which limits the utilization of this approach. Hyperhidrosis, a disease of excessive sweating, is commonly seen in young Orientals. Treatment of hyperhidrosis often involves surgical removal of the second thoracic sympathetic ganglia (T2G), which contain catecholaminergic neurons. The purpose of our study was to investigate behavioral responses and tyrosine hydroxylase (TH) immunoreactivity in hemiparkinsonian rats at different time points after transplantation of human T2G from hyperhidrotic patients. Athymic Fisher 344 rats were injected unilaterally with 6-hydroxydopamine into the medial forebrain bundle to destroy the nigrostriatal dopaminergic (DA) pathway. The effectiveness of lesions was tested by measuring methamphetamine (MA)-induced rotations. These unilaterally lesioned rats were later transplanted with T2G or T2 fiber tract (T2F) obtained from adult hyperhidrotic patients. Animals grafted with T2G showed a reduction in MA-induced rotation by 2 weeks; however, rotation returned to the pregrafting levels by 3 months. Animals receiving T2F grafts did not show any reduction of rotation over a 3-month period. Animals were later sacrificed for TH immunostaining at different time points. Tyrosine hydroxylase-positive [TH(+)] cell bodies and fibers were found in the lesioned striatum 2-4 weeks after T2G grafting, suggesting the survival of transplants. Two to 3 months after grafting, TH(+) fibers were still found in almost all the recipients. However, TH(+) cell bodies were found in only three of seven rats studied. Animals receiving T2F grafting did not show any TH immunoreactivity in the lesioned striatum over the 3-month period. These data indicate that T2G transplants from adult hyperhidrotic patients can survive and provide transient normalization of the motor behavior in the hemiparkinsonian athymic rats. Because of the short-term improvement in behavior after grafting, the use of T2G in human trials should be cautious at the present time. Further laboratory research is required.

Viability of mature superior cervical ganglia transplants in peripheral nerve of adult rat.

Allografts of mature rat superior cervical ganglia (SCG) survived for up to 120 days following transplantation to regenerating and degenerating peripheral nerves of adult rats. Transplants contained the constituents of normal superior cervical ganglia and there was evidence of outgrowth of catecholamine containing fibers from the transplants. However, fibers did not attain the length necessary to enter peripheral muscles and no muscle response could be elicited by electrical stimulation of the implanted nerve where the transplanted mature SCG was the only source of nerve fibers.

Focal circumvention of blood-brain barrier with grafts of muscle, skin and autonomic ganglia.

The efficacy with which circulating horseradish peroxidase (HRP) spreads from transplants into the brain's interstitial spaces (IS), was assessed by 3 factors: graft type, site and age. Pieces of skeletal muscle, skin or entire superior cervical ganglion (SCG) were inserted into the IV ventricle (ventricular) or substance of the brain (parenchymal). The age of the grafts, i.e. the intervals after transplantation, were 1, 3, 6 and 12 months. Generally, HRP spread into the IS to about the same extent from ventricular muscle and skin autografts--1 mm, but less from parenchymal SCG allografts--0.5 mm. The spread from all grafts--ventricular and parenchymal--diminished with time. Exudation distance from muscle was the same as that from skin grafts for the first 6 months, but by 1 year, the penetration was significantly greater from muscle than from skin transplants. The flow of HRP was more extensive from parenchymal SCG grafts than from parenchymal muscle and skin grafts at 6 and 12 months. In some of the 6 and 12 month old parenchymal grafts of muscle and skin, no detectable HRP was extravasated. HRP consistently penetrated the brain more deeply from ventricular skin and muscle grafts than from parenchymal ones because more tissue mass survived in ventricular than in parenchymal autografts. Though care was taken not to damage the brain surface during ventricular insertion, there was a consistent, vigorous, collateral sprouting of, as yet unidentified, cranial nerves. These sprouts innervated muscle and skin autografts which, consequently, were able to survive for at least 1 year and contained vessels permeable to HRP. Allografts of muscle between inbred strains did not become innervated, survived for only 2 months and contained the central, barrier type of vessels, but not their intrinsic, permeable type. Thus, it is the muscle cell or its basal lamina within muscle grafts that determines the type of surviving vessel. In SCG allografts, even when all their ganglion cells had disappeared, leaving only connective tissue, Schwann cells and their basal lamina, the ganglion's capillaries survived and remained permeable to HRP. Therefore, the characteristics of the SCG vessels are determined by the Schwann cell-fibroblast milieu rather than the neuronal one.

Growth of central substance P-containing neurons into superior cervical ganglia transplanted in the spinal cord of adult rats.

Superior cervical ganglia (SCG) contain substance P-like immunoreactive (SP-IR) fibers but not SP-IR neurons. In the present study, SCG were excised from adult rats and transplanted into the same animal's spinal thoracic cord (Th10). One or two weeks after the operation, SP-IR fibers from the host spinal cord or a higher level had grown and entered the transplanted SCG where they formed direct contacts with SCG neurons. However, these phenomena could not be observed when dorsal root ganglia (L4), which contained numerous SP-IR cells, were transplanted into their own spinal cord (Th10). This suggests that the SP-IR neuron system in the adult is able to grow "new axons' to the grafted tissue to form a "new SP-IR' neuronal circuit when the grafted tissue has lost its own SP-IR input.

Local blood flow and vascular permeability of autonomic ganglion-transplants in the brain.

The purpose of this study was to determine whether the blood vessels of transplanted neural tissue retain their functional characteristics. Quantitative autoradiography was used to measure local blood flow (F) with iodoantipyrine and the blood-to-tissue transfer constant (K) with alpha-aminoisobutyric acid in superior cervical ganglion (SCG) allografted to the surface of ventricle IV and into the cerebellum of the same rat. The F of the intraparenchymal grafts was slightly lower than that of the intraventricular grafts; F decreased between 1 and 4 weeks in SCG grafts at both sites. The permeability-surface area (PS) product of the microvessels and extraction fraction of AIB were calculated from these results and indicated restricted transvascular passage of the amino acid in both the in situ and grafted SCG. Surface area (S) and average length (L) of the microvessels were determined morphometrically and their permeability (P) was calculated from these data. Although K and PS decreased in the grafts compared to in situ SCG, a comparable decrease in S indicated that P was similar for the microvessels of both in situ and 1-week-old SCG transplants: 3.5-4.3 x 10(-6) cm/s. Between 1 and 4 weeks after transplantation, the P of the microvessels decreased to approximately 1.6-2.3 x 10(-6) cm/s without any change in S. Thus, the blood vessels of SCG grafts within or upon the brain initially retain the functional attributes of in situ SCG microvessels, but the average permeability of the graft microvessels decreases to approximately one half of the initial value by 4 weeks after transplantation.

The astroglial response to autonomic tissue grafts.

Autonomic (superior cervical) ganglia were grafted either into the IV ventricle where minimal trauma occurred or directly into the cerebral cortex which was necessarily traumatic. Previous studies have shown that host astroglia may migrate into autonomic tissue grafts. The purpose of the present study was to compare and contrast the astroglial response in allo- and autografts. By monitoring the host response in the two model sites using glial fibrillary acidic protein (GFAP) immunostaining in 1 micron plastic sections we sought to determine the role of injury stimulus in astroglial migration. In addition, these models could be used to investigate any potential differences in glial reactivity produced by allo- or autograft antigenic stimulation. In both ventricular and parenchymal locations, astroglia migrated progressively into allografts. Migration, which could have taken place along anastomotic vascular connections, began after one week and was continual, eventually replacing graft neural tissue. Astrocytic processes appeared enlarged and highly immunoreactive only as they entered the allografts or were in close association with the choroid plexus; adjacent host astrocytes were unaltered. Glial migration was greatly reduced in ventricular autografts but in the parenchymal site was nearly comparable to that of allografts. It was suggested that certain immunological factors may be involved in glial reactivity or migration considering the observed differences in the non-traumatic model whereas tissue damage stimulus played a major role in migration in both allo- and autografts. In no instances were typical astrocytic end-feet found on the autonomic graft vessels. The host astrocytic response to grafted autonomic tissue occurred significantly later (5-7 days) than the host endothelial response. This observation indicates that the graft vessels were original, intrinsic ones and the astrocytic invasion played no role in influencing endothelium with regards to brain-barrier properties.

Functional recovery in a rat model of Parkinson's disease following transplantation of cultured human sympathetic neurons.

Rats subjected to a unilateral 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal dopamine pathway were given transplants of cultured fetal human sympathetic neurons. Amphetamine-induced turning behavior in these rats was reversed by the transplants after 1.5-4.5 months. The presence of transplanted neurons and their processes was demonstrated by immunohistochemistry for tyrosine hydroxylase.

Autotransplantation of the superior cervical ganglion into the brain. A possible therapy for Parkinson's disease.

The superior cervical ganglion (SCG) of rats was transplanted into their own parietal cortex. Four weeks after implantation, catecholamine histofluorescence revealed many transplanted catecholamine cells in the cortex. However, no fibers extended from the transplanted tissue to the cerebral cortex. In a second group of rats which had been pretreated with 6-hydroxydopamine (a specific neurotoxin to the catecholamine neuron), some showed extension of catecholamine fibers to the cerebral cortex. To simulate an animal model of Parkinson's disease, MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) was administered to five monkeys. Two weeks after MPTP administration, dopamine terminals in the caudate nucleus disappeared. After autotransplantation of the SCG into the caudate nucleus of these monkeys, many of the transplanted SCG cells extended axons beyond the graft into the caudate nucleus. These results show that transplanted SCG cells survived well in the brain. Under special circumstances, such as a shortage of catecholamine in the brain, implanted SCG cells extended their axons into the brain. It is suggested that autotransplantation of SCG grafts may be a new therapy for Parkinson's disease.

Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease.

OBJECT: There is growing evidence to indicate that tissue transplantation can potentially be a restorative neurosurgical treatment for patients with Parkinson disease (PD). In this study the authors investigated the clinical effect of unilateral intrastriatal grafting of autologous sympathetic neurons in patients with PD. METHODS: Four patients with PD who had been observed for 1 year after graft placement of autologous sympathetic neurons were selected for an analysis of the effect of that procedure. Sympathetic ganglion tissue was endoscopically excised from the thoracic sympathetic trunk and grafted into the unilateral caudate head and putamen of the PD patients. No changes were made in the patients' preoperative regimens of antiparkinsonian medications, and clinical evaluations were made principally according to those established by the Core Assessment Program for Intracerebral Transplantation Committee. Whereas the sympathetic neuron grafts failed to affect clinical scores reflecting the patients' motor performance, which was evaluated during either the "on" or "off' phases, the grafts significantly increased the duration of the levodopa-induced on period with consequent reduction in the percentage of time spent in the off phase. This beneficial effect may be explained by the results of the present in vitro experiment, which show that human sympathetic neurons have the ability to convert exogenous levodopa to dopamine and to store this synthesized dopamine. CONCLUSIONS: Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits.

[Improvement of memory function of fornix-fimbria transected rats by transplantation of the superior cervical ganglion into hippocampus].

Memory impairments of passive avoidance response were observed in 38 Wistar rats with bilateral fornix-fimbria transection. After fornix-fimbria lesions the degree of performance decreased from 65.3% to 13.6% (P < 0.01). Autotransplantation of superior cervical ganglion (SCG) into bilateral dorsal hippocampi improved memory function to a considerable extent. In the end of the behavioral experiments, implanted rats were sacrificed for histofluorescence study of grafts and measurement of norepinephrine (NA) content in the hippocampus. These experiments showed that the hippocampal NA content in implanted rats was considerably higher than that in untransplanted fornix-fimbria transected rats and consequently suggested that improvement of memory function was to some extent due to supplement of monoamine transmitter by the transplanted SCG.

[A pathological study on the autotransplantation of monkey's cervical sympathetic ganglion into brain for the treatment of Parkinson's disease].

OBJECTIVE: In order to find out evidences in explicating whether the transplanted ganglion cells can be kept surviving longer in the brain and to find out an ideal transplantation way for the surgical treatment of Parkinson's disease. METHODS: Cervical sympathetic ganglions autotransplantation into the caudate nuclei of the brain in 9 rhesus monkeys known to have the symptoms and signs of the Parkinson's disease beforehand induced by using 1-methy1-4-phen-1, 2, 3, 6-tetrahydropynidne (MPTP) and in addition, muscle tendon tissue was also grafted for comparison. The experimental animals were followed up for 2 years. All the specimens taken were processed and prepared in continuous frozen sections for H & E, glyoxlyic acid induced dopamine fluorescence and immunochemistry stainings including anti-chromogranin A, synaptophysin, neurofilament, NSE, GFAP as markers. RESULTS: Two years after the autotransplantation operation, there were still surviving ganglion cells left in the caudate nuclei. The grafted ganglion cells were connected by the neurodendrites with the brain tissue which showed dopamine fluorescence positive and also had expression of chromogramin A, synaptophysin and neurofilaments. CONCLUSIONS: The grafted cells survived in the brain over 2 years. It's considered that the sympathetic ganglion is the first choice in comparing with other tissues as the graft for the surgical treatment of Parkinson's disease. Continuous frozen sections accompanying with inducing fluorescence and immunohistochemistry staining are seemed reliable as the parameters in checking the result after neural transplantation.

[Transplantation of the superior cervical ganglion into the brain--a new experimental therapy of Parkinson disease].

To supplement catecholamine deficit in the brain with Parkinson disease, we have aimed to transplant the superior cervical ganglion (SCG), which contains norepinephrine and dopamine, into the brain. 1. Transplantation of SCG into rat cerebral cortex SCG was transplanted into the same rat's parietal cortex. Three weeks after the transplantation, catecholamine histofluorescence revealed many transplanted catecholamine cells in the cortex. However, no fibers extended from the transplanted tissue to the cerebral cortex. Some catecholamine fibers extended to the cerebral cortex where 6-OHDA (a specific neurotoxin to the catecholamine neuron) had been pretreated. 2. Transplantation of SCG into the caudate nucleus of MPTP-induced Parkinson monkey For animal model of Parkinson disease, MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) was administered to 5 monkeys. Tow weeks after MPTP administration, dopamine terminals disappeared in the caudate nucleus. After transplantation of SCG in the same animal, many transplanted SCG cells extended their axons to the caudate nucleus. The present results showed that transplanted SCG cells were well survived in the brain. Under a special circumstance such as shortage of catecholamine in the brain, transplanted SCG cells extended their axons into the brain. It is suggested that the transplantation of SCG can be a new therapy for Parkinson disease.

[Transplantation of nerve tissue]. / Transplantatsiia nervnoi tkani.

The results of transplantation of various parts of the central and peripheral nervous system are considered. Transplantation of nerve trunks is used clinically, and heterogenous regeneration of the nerves results in reinnervation of tissues and organs. The spinal ganglion transplantation is successfully used in experiments with both embryonic and mature differentiated neurons. Transplantation of different parts of the cortex, some subcortical structures, hyppocampus, hypothalamus, cerebellum and the spinal cord is made using immature neurons. Some attempts have been made to transplant the nerve tissue grown in vitro into a host.