Autotransplantation of the superior cervical ganglion into the brain

1988 ◽  
Vol 68 (6) ◽  
pp. 955-959 ◽  
Author(s):  
Toru Itakura ◽  
Ichiro Kamei ◽  
Kunio Nakai ◽  
Yutaka Naka ◽  
Kazuo Nakakita ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebral Cortex ◽  
Caudate Nucleus ◽  
Superior Cervical Ganglion ◽  
Content Type ◽  
Cervical Ganglion ◽  
6 Hydroxydopamine ◽  
The Brain ◽  
Fine Print

✓ 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.

Preparation of adrenal medullary tissue for transplantation in Parkinson's disease: a new procedure

1989 ◽  
Vol 71 (3) ◽  
pp. 452-454 ◽  
Author(s):  
Juan J. López-Lozano ◽  
Begoña Brera ◽  
Javier Abascal ◽  
Gonzalo Bravo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adrenal Gland ◽  
Caudate Nucleus ◽  
Culture Medium ◽  
Content Type ◽  
Potential Value ◽  
Medullary Tissue ◽  
And Storage ◽  
Fine Print

✓ The authors describe a technique by which adrenal medullary tissue can be easily dissected from the adrenal cortex. The method involves perfusion with Locke's modified buffer, dissection of adrenal gland in buffer free of calcium or magnesium, and storage in a culture medium before implantation into the caudate nucleus of patients with Parkinson's disease. This method seems to increase the viability and purity of adrenal medullary tissue. The results obtained in 15 parkinsonian patients implanted with perfused adrenal medulla indicate the potential value of this technique.

Fatal cyst formation after fetal mesencephalic allograft transplant for Parkinson's disease

1998 ◽  
Vol 89 (4) ◽  
pp. 592-598 ◽  
Author(s):  
Adam N. Mamelak ◽  
Faye A. Eggerding ◽  
Daniel S. Oh ◽  
Erika Wilson ◽  
Richard L. Davis ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Choroid Plexus ◽  
Cyst Formation ◽  
Mural Nodule ◽  
Content Type ◽  
Allograft Tissue ◽  
The Brain ◽  
Tissue Transplant ◽  
Fine Print

Object. In recent years, fetal mesencephalic tissue transplant for the treatment of Parkinson's disease (PD) has been demonstrated to hold promise, but potential complications related to growth of allograft tissue have not been well described. This report explores the development and possible causation of a fatal cyst arising from a fetal transplant in the brain. Methods. The authors report the case of a 52-year-old woman who underwent bilateral putamenal fetal mesencephalic allograft transplant for PD at another hospital. Twenty-three months later she presented to the authors' institution in a coma. Admission computerized tomography and magnetic resonance (MR) studies revealed a contrast-enhancing mural nodule and associated large cyst arising from the left putamen and causing brainstem compression. Despite surgical decompression of the cyst, the patient did not regain consciousness. Biopsy and autopsy specimens were obtained, along with an analysis of the cyst fluid. Genotyping of the nodule and the patient's peripheral lymphocytes by using polymerase chain reaction—based microsatellite analysis was also performed. Biopsy samples and autopsy histopathological studies showed inflammatory cells, hemosiderin-laden macrophages, and astrocytosis. Scattered neurons and multiple rests of choroid plexus were also noted. The cyst had a thin wall and contained liquid that was identical in composition to cerebrospinal fluid (CSF). Genotyping demonstrated the presence of alleles in the nodule DNA that were not present in lymphocytic DNA, indicating that the nodule contained allograft tissue. Conclusions. The authors hypothesize that the choroid plexus tissue contained in the allograft resulted in CSF production and cyst formation at the transplant site, ultimately leading to the patient's herniation syndrome. The clinical history and large size of the mural nodule indicate slow growth of this allograft site and cyst over time. This case demonstrates that unusual patterns of tissue growth can occur in the brain after fetal tissue transplant and emphasizes the need for long-term monitoring of posttransplant patients by means of MR imaging. Cell sorting should be considered to ensure transplant of pure neuronal and astroglial populations.

Long-term improvement in patients with severe Parkinson's disease after implantation of fetal ventral mesencephalic tissue in a cavity of the caudate nucleus: 5-year follow up in 10 patients

1997 ◽  
Vol 86 (6) ◽  
pp. 931-942 ◽  
Author(s):  
Juan J. López-Lozano ◽  
Gonzalo Bravo ◽  
Begoña Brera ◽  
Isabel Millán ◽  
Jose Dargallo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caudate Nucleus ◽  
Adrenal Medulla ◽  
Open Surgery ◽  
Clinical Symptoms ◽  
Content Type ◽  
Ventral Mesencephalic ◽  
Fine Print

✓ Different groups worldwide have observed in recent years that stereotactic implantation of fetal tissue can ameliorate the clinical symptoms of Parkinson's disease. The authors therefore investigated whether implantation of fetal ventral mesencephalic (FVM) tissue via open surgery is also capable of producing an improvement and whether this improvement is transient or long lasting. The authors report their findings in a 5-year follow-up study in 10 patients with Hoehn and Yahr Grade IV or V Parkinson's disease in whom a single FVM graft was implanted in a cavity created in the right caudate nucleus. The results indicate that the implants improved motor function and that clinical recovery persisted in seven of the 10 patients 5 years after implantation. Amelioration was observed in both the on and off phases and was accompanied by a 64% reduction in the levodopa dose and withdrawal of the dopamine agonist. The on phase was prolonged from 39% of the waking day to 72%, with reduced intensity and duration of dyskinesias. All symptoms that were analyzed showed improvement, although they differed in intensity and time of onset. The course of improvement seemed to be stepwise, with significant improvement between 5 and 7 months postimplantation followed by two waves of progress peaking in Months 15 and 36. Withdrawal of cyclosporine in three patients after more than 2 years of administration produced a decline in the patients' clinical conditions. In conclusion, the results indicate that open surgery implantation of FVM tissue in the caudate nucleus improves the clinical condition of parkinsonian patients and that this improvement can persist for at least 5 years. In comparison with two earlier series reported by the authors, which involved implants of perfused adrenal medulla and coimplantation of adrenal medulla and peripheral nerve, the course and pattern of improvement in these implant recipients suggests that their recovery can be attributed to more than one factor.

Autotransplantation of superior cervical ganglion to the caudate nucleus in three patients with Parkinson's disease (preliminary report)

1990 ◽  
Vol 13 (2) ◽  
pp. 119-122 ◽  
Author(s):  
Miklos Horvath ◽  
Emil Pasztor ◽  
Miklos Palkovits ◽  
Andras Solyom ◽  
Miklos Tarczy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caudate Nucleus ◽  
Superior Cervical Ganglion ◽  
Preliminary Report ◽  
Cervical Ganglion

Stereotactic pallidotomy performed without using microelectrode guidance in patients with Parkinson's disease: surgical technique and 2-year results

2000 ◽  
Vol 92 (3) ◽  
pp. 375-383 ◽  
Author(s):  
Emad N. Eskandar ◽  
Leslie A. Shinobu ◽  
John B. Penney ◽  
G. Rees Cosgrove ◽  
Timothy J. Counihan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Surgical Technique ◽  
Mr Imaging ◽  
Rating Scales ◽  
Lesion Volume ◽  
Content Type ◽  
Lesion Location ◽  
The Brain ◽  
Fine Print

Object. Pallidotomy for the treatment of medically refractory Parkinson's disease (PD) has enjoyed renewed popularity. However, the optimal surgical technique, lesion location, and long-term effectiveness of pallidotomy remain subjects of debate. In this article the authors describe their surgical technique for performing pallidotomy without using microelectrode guidance, and the clinical and radiological results of this procedure.Methods. Patients were evaluated preoperatively by using a battery of validated clinical rating scales and magnetic resonance (MR) imaging of the brain. Individuals with severe treatment-refractory idiopathic PD who were believed to be good candidates for surgery underwent computerized tomography scanning— and MR imaging—guided stereotactic pallidotomy. Intraoperative macrostimulation was used to optimize lesion placement and to avoid injury to nearby structures. Lesion location and size were calculated from MR imaging sequences of the brain obtained within the first 24 hours after surgery and again 3 months later. Clinical examinations were conducted at 1.5, 3, 6, 12, and 24 months after surgery.Seventy-five patients (mean age 61 years, range 38–79 years) underwent unilateral pallidotomy. Significant improvements were observed in the “off” period scores for the activities of daily living portion of the Unified Parkinson's Disease Rating Scale (UPDRS), the UPDRS motor scores, total “on” time, levodopa-induced dyskinesias, and contralateral tremor. These improvements were maintained 24 months postoperatively. The mean lesion volume measured on the immediate postoperative MR image was 73 ± 5.4 mm3. Radiological analysis suggests that initial lesion volume does not predict outcome. The only permanent major complication was a single visual field defect.Conclusions. Pallidotomy performed without using microelectrode guidance is a safe and effective treatment for selected patients with medically refractory PD.

Clinical outcome of cotransplantation of peripheral nerve and adrenal medulla in patients with Parkinson's disease

1999 ◽  
Vol 90 (5) ◽  
pp. 875-882 ◽  
Author(s):  
Juan J. López-Lozano ◽  
Gonzalo Bravo ◽  
Javier Abascal ◽  
Begoña Brera ◽  
Isabel Millan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Peripheral Nerve ◽  
Caudate Nucleus ◽  
Adrenal Medulla ◽  
Intercostal Nerve ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Content Type ◽  
Fine Print

Object. Transplants of adrenal medulla (AM) and fetal ventral mesencephalon (FVM) are currently being tested as therapeutic alternatives in patients with Parkinson's disease (PD). At the Clínica Puerta de Hierro in Madrid, a controlled clinical trial is underway to establish which donor tissue, if any, is the best for open surgical implantation in patients with PD.Methods. Since 1987, varying degrees of clinical improvement have been achieved in Grade IV and V parkinsonian patients by implanting perfused AM and FVM into the right caudate nucleus. To investigate further whether implantation of different types of donor tissues results in qualitatively and quantitatively different degrees of recovery, four patients with Grade IV or V PD received implants of pre-coincubated autologous AM and intercostal nerve in the caudate nucleus. Four nonsurgically treated patients served as a control group. Three years posttransplantation, longer on phases (46.2% ± 10.4% of the day presurgery to 87.5% ± 10.4% of the day 36 months postsurgery) and improved symptoms in on and off phases persist in all four cases, with reduced dyskinesias (67.1% ± 9.2% of the day in on phases presurgery to 17% ± 13.8% of the day in on phases 36 months postsurgery). Progress appears to be stepwise, starting within weeks of tranplantation and becoming clinically significant in the 2nd and 3rd months (similar to our AM- and sooner than in our FVM-implanted patients), followed by a period of stability and, after a second wave of improvement 12 to 18 months posttransplantation (similar to FVM implants), has continued (87.5 ± 7 points presurgery to 46 ± 5.6 points 36 months postsurgery). In the experimental group, doses of levodopa have been reduced by more than 60% and dopamine agonist use has not resumed. In contrast, there have been no significant clinical changes in the control group.Conclusions. Implantation of tissue other than fetal tissue can promote a long-term improvement in the clinical symptomatology of seriously disabled parkinsonian patients. This finding is supported by the autopsy report of a patient with PD who had undergone grafting of AM plus peripheral nerve in which it was demonstrated that a large number of tyrosine hydroxylase—positive cells survive 1 year after implantation. In addition, there was a dense network of host dopaminergic fibers around the graft.

Superior cervical ganglion regenerating axons through peripheral nerve grafts and reversal of behavioral deficits in hemiparkinsonian rats

1996 ◽  
Vol 84 (3) ◽  
pp. 487-493 ◽  
Author(s):  
Roberto Pallini ◽  
Eduardo Fernandez ◽  
Liverana Lauretti ◽  
Elisabetta Dell'Anna ◽  
Frank La Marca ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Superior Cervical Ganglion ◽  
Light And Electron Microscopy ◽  
Cervical Region ◽  
Adult Rats ◽  
Content Type ◽  
Cervical Ganglion ◽  
The Right ◽  
The Brain ◽  
Fine Print

✓ The superior cervical ganglion (SCG) has been grafted to the brain of adult rats in an attempt to reverse the parkinsonian syndrome that follows destruction of central dopamine systems. However, the main limitation to this approach is the massive cell death that occurs in the grafted SCG after direct transplantation into the brain. In adult rats, 6-hydroxydopamine (6-OHDA) was stereotactically injected into the right substantia nigra (SN). One month later, dopamine denervation was assessed using the apomorphine-induced rotational test. In rats with a positive test, an autologous peripheral nerve (PN) graft was tunneled from the right cervical region to the ipsilateral parietal cortex. One end of the PN graft was sutured to the transected postganglionic branch of the SCG and the other end was inserted into a surgically created cortical cavity. The apomorphine test was repeated at 3 days and again at 1, 3, and 5 months after surgery. The brain, SCG, and PN graft were studied under light and electron microscopy and with the tyrosine hydroxylase immunohistochemical and horseradish peroxidase tracing methods. Three days after grafting, there were no significant differences on the apomorphine test as compared to the preoperative test. Conversely, 1, 3, and 5 months after grafting, the number of rotations was reduced by 69% (± 20.2), 66.6% (± 17.1), and 72.5% (± 11.3), respectively. Control rats that received a free PN graft to the brain and underwent section of the postganglionic branch of the SCG did not show significant changes on the apomorphine test after surgery. Histological examination revealed that the PN graft was mostly reinnervated by amyelinic axons of small caliber. Approximately 40% of the SCG neuronal population that normally projects to the postganglionic branch survived axotomy and regenerated the transected axons into the PN graft. Axons arising from the SCG elongated the whole length of the graft, crossed the graft—brain interface and extended into brain regions adjacent to the denervated striatum up to 2037 µm from the graft insertion site. This work shows that the ingrowth of catecholamine-regenerating axons from the SCG to dopamine-depleted brain parenchyma significantly reduces behavioral abnormalities in hemiparkinsonian rats. This effect cannot be ascribed either to the brain cavitation or to the PN tissue placement in the brain.

Gamma knife radiosurgery as a lesioning technique in movement disorder surgery

1998 ◽  
Vol 89 (2) ◽  
pp. 183-193 ◽  
Author(s):  
Ronald F. Young ◽  
Anne Shumway-Cook ◽  
Sandra S. Vermeulen ◽  
Peter Grimm ◽  
John Blasko ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Movement Disorder ◽  
Gamma Knife ◽  
Movement Disorders ◽  
Gamma Knife Radiosurgery ◽  
Safety And Efficacy ◽  
Content Type ◽  
Fine Print

Object. To increase knowledge of the safety and efficacy of the use of gamma knife radiosurgery in patients with movement disorders, the authors describe their own experience in this field and include blinded independent assessments of their results. Methods. Fifty-five patients underwent radiosurgical placement of lesions either in the thalamus (27 patients) or globus pallidus (28 patients) for treatment of movement disorders. Patients were evaluated pre- and postoperatively by a team of observers skilled in the assessment of gait and movement disorders who were blinded to the procedure performed. The observers were not associated with the surgical team and concomitantly and blindly also assessed a group of 11 control patients with Parkinson's disease who did not undergo any surgical procedures. All stereotactic lesions were made with the Leksell gamma unit using the 4-mm secondary collimator helmet and a single isocenter with maximum doses from 120 to 160 Gy. Clinical follow-up evaluation indicated that 88% of patients who underwent thalamotomy became tremor free or nearly tremor free. Statistically significant improvements in performance were noted in the independent assessments of Unified Parkinson's Disease Rating Scale (UPDRS) scores in the patients undergoing thalamotomy. Of patients undergoing pallidotomy who had exhibited levodopainduced dyskinesias, 85.7% had total or near-total relief of that symptom. Clinical assessment indicated improvements in bradykinesia and rigidity in 64.3% of patients who underwent pallidotomy. Independent blinded assessments did not reveal statistically significant improvements in Hoehn and Yahr scores or UPDRS scores. On the other hand, 64.7% of patients showed improvements in subscores of the UPDRS, including activities of daily living (58%), total contralateral score (58%), and contralateral motor scores (47%). Total ipsilateral score and ipsilateral motor scores were both improved in 59% of patients. One (1.8%) of 55 patients experienced a homonymous hemianopsia 9 months after pallidotomy due to an unexpectedly large lesion. No other complications of any kind were seen. Neuropsychological test scores that were obtained for the combined pallidotomy and thalamotomy treatment groups preoperatively and at 6 months postoperatively demonstrated an absence of cognitive morbidity. Follow-up neuroimaging confirmed correct lesion location in all patients, with a mean maximum deviation from the planned target of 1 mm in the vertical axis. Measurements of lesions at regular intervals on postoperative magnetic resonance images demonstrated considerable variability in lesion volumes. The safety and efficacy of functional lesions made with the gamma knife appear to be similar to those made with the assistance of electrophysiological guidance with open functional stereotactic procedures. Conclusions. Functional lesions may be made safely and accurately using gamma knife radiosurgical techniques. The efficacy is equivalent to that reported for open techniques that use radiofrequency lesioning methods with electrophysiological guidance. Complications are very infrequent with the radiosurgical method. The use of functional radiosurgical lesioning to treat movement disorders is particularly attractive in older patients and in those with major systemic diseases or coagulopathies; its use in the general movement disorder population seems reasonable as well.

Reversal of experimental parkinsonism by using selective chemical ablation of the medial globus pallidus

1999 ◽  
Vol 90 (5) ◽  
pp. 928-934 ◽  
Author(s):  
Daniel M. Lieberman ◽  
Marc-Etienne Corthesy ◽  
Alex Cummins ◽  
Edward H. Oldfield
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Kainic Acid ◽  
Globus Pallidus ◽  
Optic Tract ◽  
High Flow ◽  
Content Type ◽  
Chemical Ablation ◽  
Selective Chemical ◽  
Fine Print

Object. Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined the feasibility of convection-enhanced distribution of a neurotoxin by high-flow microinfusion to ablate the neurons of the GPm selectively and reverse experimental Parkinson's disease (akinesia, tremor, and rigidity).Methods. Initially, to test the feasibility of this approach, the GPms of two naive rhesus macaques were infused with kainic acid or ibotenic acid through two cannulas that had been placed using the magnetic resonance imaging—guided stereotactic technique. Two weeks later the animals were killed and their brains were examined histologically to determine the presence of neurons in the GPm and the integrity of the optic tract and the internal capsule. To examine the therapeutic potential of this paradigm, unilateral experimental Parkinson's disease was induced in six macaques by intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and their behavior was studied for 12 weeks after chemopallidotomy was performed using kainic acid (three animals) or control infusion (three animals).Conclusions. Chemopallidotomy using kainic acid permanently reversed the stigmata of MPTP-induced parkinsonism. By contrast, the control animals exhibited a transient recovery following intrapallidal infusion and then relapsed back to their baseline state. The use of high-flow microinfusion of selectively active toxins has the potential for treatment of Parkinson's disease and, by expanding the range of approachable targets to include large nuclei, for broad applications in clinical and experimental neuroscience.

scholarly journals AnIn VivoMicrodialysis Study of FLZ Penetration through the Blood-Brain Barrier in Normal and 6-Hydroxydopamine Induced Parkinson’s Disease Model Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jinfeng Hou ◽  
Qian Liu ◽  
Yingfei Li ◽  
Hua Sun ◽  
Jinlan Zhang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Time Curve ◽  
Liquid Chromatography Tandem Mass ◽  
Bbb Permeability ◽  
6 Hydroxydopamine ◽  
The Brain ◽  
Active Substances

FLZ (N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide) is a novel synthetic squamosamide derivative and a potential anti-Parkinson’s disease (PD) agent. The objective of the present study was to investigate the penetration of free FLZ across the BBB and the effects of P-gp inhibition on FLZ transport in normal and 6-hydroxydopamine (6-OHDA) induced PD model rats.In vivomicrodialysis was used to collect FLZ containing brain and blood dialysates following intravenous (i.v.) drug administration either with or without pretreatment with the specific P-gp inhibitor, zosuquidar trihydrochloride (zosuquidar·3HCl). A sensitive, rapid, and reliable ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to quantitate free FLZ levels in the dialysates. No significant differences were observed in the brain/blood FLZ area under the concentration-time curve (AUC) ratio between normal and PD model rats. However, pretreatment with zosuquidar·3HCl markedly increased the AUC ratio in both rat models. In addition, FLZ penetration was similar in zosuquidar·3HCl-pretreated normal and PD rats. These results suggest that P-gp inhibition increases BBB permeability to FLZ, thereby supporting the hypothesis that P-gp normally restricts FLZ transfer to the brain. These findings could provide reference data for future clinical trials and may aid investigation of the BBB permeability of other CNS-active substances.

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