| 1. |
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| 2. |
- Duan, W M, et al.
(författare)
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Sequential intrastriatal grafting of allogeneic embryonic dopamine-rich neuronal tissue in adult rats : will the second graft be rejected?
- 1993
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Ingår i: Neuroscience. - 0306-4522. ; 57:2, s. 74-261
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Tidskriftsartikel (refereegranskat)abstract
- An important issue in clinical neural grafting is whether a second instriatial allograft can survive well in a patient who has received an allograft before. In this study, the survival, immunogenicity and function of intrastriatal grafts of allogeneic or syngeneic embryonic dopamine-rich tissue in rats which had previously received either an intrastriatal allo- or syn-graft or sham injections were examined. The first graft tissue was taken from inbred Lewis or Sprague-Dawley rat embryos and grafted into an intact striatum of adult Sprague-Dawley rats subjected to a unilateral 6-hydroxydopamine lesion on the contralateral side. Eight weeks after the first transplantation, either allogeneic or syngeneic tissue was grafted as dissociated tissue into the dopamine depleted striatum. The function of the second grafts was assessed by rotational asymmetry at two different time points, i.e. eight and 14 weeks after the second transplantation. There were significant reductions of rotational asymmetry in all groups over time, but no significant difference between groups. Tyrosine hydroxylase immunocytochemistry was used to assess dopamine cell survival and graft size. Statistical analysis revealed no significant differnce in the mean number of tyrosine hydroxylase immunoreactive cells or the mean volume of the second grafts placed on the right side (lesioned side) between groups. Monoclonal antibodies were used to evaluate cellular immune reactions and the major histocompatibility complex class I and class II expression in and around grafts. No major histocompatibility complex class I expression was seen in any of the graft combinations. The expression of the major histocompatibility complex class II antigens was generally higher in patches in and around the second allograft of rats which had previously received an allograft than that in and around any other type of grafts. However, the expression of the major histocompatibility complex class II antigens was low throughout the grafts and did not appear as marked perivascular infiltrates. All the major histocompatibility complex class II positive cells displayed a microglia-like morphology, supported by the parallel microglia and macrophage-specific OX-42 immunostaining. The results show that there is no marked on-going immune reactions in or around the implantation site in any group fourteen weeks after a second transplantation. It may be concluded, therefore, that sequential allografting, using stereotaxic implantation of dissociated embryonic neural tissue into the striatal parenchyma, is possible to perform without a major risk of graft rejection, provided that an atraumatic technique is used.
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| 3. |
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| 4. |
- Johansson, K, et al.
(författare)
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Can sensory stimulation improve the functional outcome in stroke patients?
- 1993
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Ingår i: Neurology. - 1526-632X. ; 43:11, s. 2189-2192
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Tidskriftsartikel (refereegranskat)abstract
- After obtaining informed consent, we randomized 78 patients with severe hemiparesis of the left or right side within 10 days of stroke onset: 40 to a control group receiving daily physiotherapy and occupational therapy, and 38 to a group that, in addition, we treated with sensory stimulation (acupuncture) twice a week for 10 weeks. The median age was 76 years for both groups. Motor function, balance, and ADL (Barthel's Index) were assessed before the start of treatment and at 1 and 3 months after stroke onset; ADL was also assessed after 12 months. We assessed the quality of life (QL) using the Nottingham Health Profile 3, 6, and 12 months after stroke onset. Patients given sensory stimulation recovered faster and to a larger extent than the controls, with a significant difference for balance, mobility, ADL, QL, and days spent at hospitals/nursing homes. Whether acupuncture per se is responsible for the differences requires further study.
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| 5. |
- Karki, A, et al.
(författare)
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Tirilazad reduces brain edema after middle cerebral artery ligation in hypertensive rats
- 1994
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Ingår i: Acta Neurochirurgica, Supplement. - 0065-1419. ; 60, s. 3-310
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Tidskriftsartikel (refereegranskat)abstract
- Tirilazad (3 mg/kg i.v.) or vehicle was given 10 min, 3 and 12 hours after ligation of the right middle cerebral artery in male spontaneously hypertensive rats (n = 12 in each group). Brain specific gravity was determined in 23 predetermined cortical regions covering the core and penumbra areas 24 hours after the occlusion. The specific gravity was significantly higher in tirilazad-treated rats than in controls (p < 0.0001). When individual regions of the two groups were compared, the difference was significant in 9 of the 23 samples predominantly, but not exclusively, in the penumbra zone.
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| 6. |
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| 7. |
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| 8. |
- Lindvall, O, et al.
(författare)
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Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease
- 1994
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134. ; 35:2, s. 80-172
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Tidskriftsartikel (refereegranskat)abstract
- Two patients with idiopathic Parkinson's disease (Patients 3 and 4 in our series) were followed up to 3 years after grafting of human embryonic dopamine-rich mesencephalic tissue unilaterally into the putamen. During the first postoperative year both patients showed significant amelioration of parkinsonian symptoms and increased 6-L-[18F]-fluorodopa uptake in the grafted putamen, as assessed with positron emission tomography. Three years after grafting the patients still exhibited increased fluorodopa uptake in the grafted putamen and significant clinical improvements, evidenced by a reduction of the severity of symptoms and of the time spent in the "off" phase, and by a prolongation of the effect of a single dose of L-dopa. Between 1 and 3 years after surgery, Patient 3 showed only minor changes of parkinsonian symptoms on the side contralateral to the graft, whereas there was a worsening on the ipsilateral side. Fluorodopa uptake decreased in the nongrafted putamen but was unchanged in the grafted putamen. Patient 4 continued to improve after the first postoperative year and L-dopa was withdrawn after 32 months. The reduction of parkinsonian symptoms on the side contralateral to the graft became more pronounced between 1 and 3 years after surgery. Fluorodopa uptake further increased in the grafted putamen, whereas no change was detected on the non-grafted side. These results indicate that grafts of embryonic dopamine neurons can survive, grow, and exert functional effects up to at least 3 years after surgery in the parkinsonian brain, despite an ongoing disease process leading to degeneration of the intrinsic dopamine system.
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| 9. |
- Lindvall, O, et al.
(författare)
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Grafts of fetal dopamine neurons survive and improve motor function in Parkinson's disease
- 1990
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 247:4942, s. 7-574
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Tidskriftsartikel (refereegranskat)abstract
- Neural transplantation can restore striatal dopaminergic neurotransmission in animal models of Parkinson's disease. It has now been shown that mesencephalic dopamine neurons, obtained from human fetuses of 8 to 9 weeks gestational age, can survive in the human brain and produce marked and sustained symptomatic relief in a patient severely affected with idiopathic Parkinson's disease. The grafts, which were implanted unilaterally into the putamen by stereotactic surgery, restored dopamine synthesis and storage in the grafted area, as assessed by positron emission tomography with 6-L-[18F]fluorodopa. This neurochemical change was accompanied by a therapeutically significant reduction in the patient's severe rigidity and bradykinesia and a marked diminuation of the fluctuations in the patient's condition during optimum medication (the "on-off" phenomenon). The clinical improvement was most marked on the side contralateral to the transplant.
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| 10. |
- Lindvall, O, et al.
(författare)
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In reply : Fetal brain grafts and Parkinson's disease
- 1990
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 250:4986, s. 1435-1435
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Lindvall, O, et al.
(författare)
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Transplantation of fetal dopamine neurons in Parkinson's disease : one-year clinical and neurophysiological observations in two patients with putaminal implants
- 1992
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 31:2, s. 65-155
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Tidskriftsartikel (refereegranskat)abstract
- Ventral mesencephalic tissue from aborted human fetuses (age, 6-7 weeks' postconception) was implanted unilaterally into the putamen using stereotaxic surgery in 2 immunosuppressed patients (Patients 3 and 4 in our series) with advanced idiopathic Parkinson's disease. Tissue from 4 fetuses was grafted to each patient. Compared with our previous 2 patients, the following changes in the grafting procedure were introduced: the implantation instrument was thinner, more tissue was placed in the operated structure, and the time between abortion and grafting was shorter. There were no postoperative complications. Both patients showed a gradual and significant amelioration of parkinsonian symptoms (most marked in Patient 3) starting at 6 and 12 weeks after grafting, respectively, reaching maximum stability at approximately 4 to 5 months; patients remained relatively stable thereafter during the 1-year follow-up period. Clinical improvement was observed as a reduction of the time spent in the "off" phase and the number of daily "off" periods; a lessening of bradykinesia and rigidity during the "off" phase, mainly but not solely on the side contralateral to the graft; and a prolongation and change in the pattern of the effect of a single dose of L-dopa. Neurophysiological measurements revealed a more rapid performance of simple and complex arm and hand movements bilaterally, but primarily contralateral to the graft. The results indicate that patients with Parkinson's disease can show significant and sustained improvement of motor function after intrastriatal implantation of fetal dopamine-rich mesencephalic tissue. The accompanying paper by Sawle and colleagues describes the results of repeated positron emission tomography scans in these patients.
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| 12. |
- Nakao, Naoyuki, et al.
(författare)
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Lazaroids improve the survival of grafted rat embryonic dopamine neurons
- 1994
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 91:26, s. 12-12408
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Tidskriftsartikel (refereegranskat)abstract
- In rodent models of Parkinson disease in which transplants of dissociated rodent and human embryonic mesencephalic tissue, rich in dopamine neurons, have been studied, only 5-20% of the dopamine neurons survive the implantation procedure. We have investigated the effects of inhibiting free radical generation with two lazaroids, U-74389G and U-83836E, on the survival of embryonic rat dopamine neurons. U-74389G is a 21-aminosteroid, and U-83836E combines the piperazinyl pyrimidine portion of 21-aminosteroids with the antioxidant ring of alpha-tocopherol. In an initial study, we found that the lazaroids markedly prolonged the period after tissue dissociation that an embryonic mesencephalic cell suspension exhibits high cell viability in vitro, as assessed by using a dye exclusion method. In a second series of experiments, addition of lazaroids to dissociated mesencephalic graft tissue increased the yield of surviving rat dopamine neurons 2.6-fold after implantation in the dopamine-denervated rat striatum. The improved survival correlated with an earlier onset of graft-induced functional effects in the amphetamine-induced rotation test. Thus, inhibition of free radical generation can significantly increase the yield of grafted embryonic dopamine neurons. Addition of lazaroids to the graft preparation is a relatively simple modification of the transplantation protocol and could readily be applied in a clinical setting. Moreover, since iron-dependent lipid peroxidation has been suggested to play a role in the death of nigral dopamine neurons in Parkinson disease and lazaroids are particularly potent inhibitors of such processes, the findings may have implications for the pathogenesis of this disease.
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| 13. |
- Sawle, G V, et al.
(författare)
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Transplantation of fetal dopamine neurons in Parkinson's disease : PET [18F]6-L-fluorodopa studies in two patients with putaminal implants
- 1992
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 31:2, s. 73-166
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Tidskriftsartikel (refereegranskat)abstract
- Two patients with Parkinson's disease who underwent implantation of fetal mesencephalic tissue into the putamen were serially studied using positron emission tomography and [18F]6-L-fluorodopa ([18F]dopa). The uptake of [18F]dopa is related to the functional integrity of the presynaptic dopaminergic system. Preoperative studies revealed a marked decrease in putamen [18F]dopa uptake, with lesser involvement of the caudate. Two and 4 months, respectively, after operation, both patients demonstrated functional improvement, as described elsewhere. One patient was scanned 5, 8, and 13 months after the operation and the other was scanned 7 and 12 months after the operation. In both patients, [18F]dopa uptake increased within the operated putamen despite a progressive decrease in tracer uptake in the unoperated striatal structures. We believe that this increased uptake of [18F]dopa at the implantation site represents functional integrity within a surviving neural graft. While there has been little further clinical improvement beyond the fifth postoperative month, the uptake of [18F]dopa at the operation site in both patients has progressively increased. The kinetic data provide evidence of disease progression in the unoperated striatum, which, balanced against increasing graft function, may explain why clinical improvement reached a plateau within months after surgery.
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| 14. |
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| 15. |
- Widner, H, et al.
(författare)
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Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
- 1992
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 327:22, s. 63-1556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intracerebral transplantation of fetal dopaminergic neurons is a promising new approach for the treatment of Parkinson's disease. Patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) have a relatively stable lesion limited to the nigrostriatal system, rendering them ideal candidates for transplantation. Improvement of motor function after neural grafting has previously been observed in nonhuman primates with MPTP-induced parkinsonism.METHODS: We grafted human fetal tissue from the ventral mesencephalon (obtained six to eight weeks after conception) bilaterally to the caudate and putamen in two immunosuppressed patients with severe MPTP-induced parkinsonism, using a stereotaxic technique. The patients were assessed regularly with clinical rating scales, timed tests of motor performance, and [18F]fluorodopa positron-emission tomography during the 18 months before the operation and the 22 to 24 months after the operation.RESULTS: Both patients had substantial, sustained improvement in motor function and became much more independent. Postoperatively, the second patient's maintenance dose of levodopa was decreased to 150 mg daily, which was 30 percent of the original dose. Striatal uptake of fluorodopa was unchanged 5 to 6 months postoperatively but was markedly and bilaterally increased at 12 to 13 and 22 to 24 months in both patients, closely paralleling the patients' clinical improvement. There were no serious complications.CONCLUSIONS: Bilateral implantation of fetal mesencephalic tissue can induce substantial long-term functional improvement in patients with parkinsonism and severe dopamine depletion and is accompanied by increased uptake of fluorodopa by the striatum. The results in these patients resemble those obtained in MPTP-treated primates and suggest that this will be a useful model for the assessment of transplantation therapies in Parkinson's disease.
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| 16. |
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| 17. |
- Widner, H
(författare)
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NIH neural transplantation funding
- 1994
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Ingår i: Science (New York, N.Y.). - 0036-8075. ; 263:5148, s. 737-737
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Widner, H, et al.
(författare)
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Sequential intracerebral transplantation of allogeneic and syngeneic fetal dopamine-rich neuronal tissue in adult rats : will the first graft be rejected?
- 1993
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Ingår i: Cell Transplantation. - 0963-6897. ; 2:4, s. 17-307
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Tidskriftsartikel (refereegranskat)abstract
- The immune response against intracerebral grafts of allogeneic fetal dopamine-rich tissue was assessed in adult rats. Sprague-Dawley rats, now outbred, but originating from an inbred stock, were given unilateral 6-hydroxy-dopamine lesions of the mesostriatal pathway, and grafted intrastriatally with mechanically dissociated ventral mesencephalic tissue (embryonic day 13-15) obtained from an inbred Lewis strain. Graft survival was assessed by functional recovery of amphetamine-induced rotational behavior on four different occasions postsurgery, and histologically using catecholamine histofluorescence and tyrosine hydroxylase immunohistochemistry. The following groups were analysed: long-term survival of a single allogeneic graft; survival of a first allogeneic graft with a syngeneic second graft; survival of a first allograft combined with a second allogeneic graft; the survival of bilateral allogeneic grafts following a subsequent orthotopic allogeneic skin graft. Evidence for recipient immunization was obtained using an indirect fluorescent antibody detection technique, Simonsen's Spleen Index (S I) test. Viable grafts, giving rise to behavioral compensation, were present after 40 wk in rats from all groups. The "first" allograft always displayed good survival and function, even following a second intracerebral allograft. However, five of nine "second" allogeneic intracerebral grafts survived poorly. In contrast, all secondary syngeneic grafts survived well. Following the application of a subsequent orthotopic allogeneic skin graft in a subgroup of rats, there was a significantly lower survival of grafted dopamine neurons in the "first" graft.
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| 19. |
- Widner, H, et al.
(författare)
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Transplantation and surgical treatment of parkinsonian syndromes
- 1993
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Ingår i: Current Opinion in Neurology and Neurosurgery. - 0951-7383. ; 6:3, s. 9-344
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Tidskriftsartikel (refereegranskat)abstract
- Neurosurgical attempts to correct parkinsonism use strategies aimed either at alleviating the underlying dopamine deficiency or at correcting abnormal compensatory effects in neural circuits within the basal ganglia. During the review period, clinical trials of four different neurosurgical approaches were reported. These approaches are intracerebral transplantation of fetal dopamine neurons, intracerebral transplantation of adrenal medullary tissue, tremor-reducing surgical lesions in the ventrolateral thalamus, and ventroposterior pallidotomy aimed at reducing akinesia and rigidity. Experimental studies in rats and monkeys designed to explore mechanisms of graft actions were also reported.
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| 20. |
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