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Immune reactions following systemic immunization prior or subsequent to intrastriatal transplantation of allogeneic mesencephalic tissue in adult rats

We have previously found that dissociated mesencephalic tissue, which differs from the host at both major histocompatibility complex and non-major histocompatibility complex gene loci, can survive stereotaxic transplantation to the striatum of adult rats. We have now studied the outcome of intrastriatal neural allografts in rats that were systemically immunized by an orthotopic skin allograft eith

Temporal pattern of host responses against intrastriatal grafts of syngeneic, allogeneic or xenogeneic embryonic neuronal tissue in rats

The host response to immunologically incompatible intrastriatal neural grafts was studied using immunohistochemical techniques. Dissociated ventral mesencephalic tissue from embryonic donors of either syngeneic, allogeneic or xenogeneic (mouse) origin was stereotaxically implanted into adult rats. The brains were analysed 4 days, 2 weeks or 6 weeks after grafting with antibodies against the follow

Lazaroids improve the survival of grafted rat embryonic dopamine neurons

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 neuro

Evidence for long-term survival and function of dopaminergic grafts in progressive Parkinson's disease

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

Tirilazad reduces brain edema after middle cerebral artery ligation in hypertensive rats

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 th

Sequential intrastriatal grafting of allogeneic embryonic dopamine-rich neuronal tissue in adult rats : will the second graft be rejected?

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

Sequential intracerebral transplantation of allogeneic and syngeneic fetal dopamine-rich neuronal tissue in adult rats : will the first graft be rejected?

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

Transplantation and surgical treatment of parkinsonian syndromes

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, intra

Expression of platelet-derived growth factor in and around intrastriatal embryonic mesencephalic grafts

The expression of platelet-derived growth factor (PDGF) was investigated in the embryonic donor tissue and surrounding host brain before and after intracerebral transplantation in a rat model of Parkinson's disease (PD). Ventral mesencephalic tissue from E13-E15 rat embryos was dissociated and implanted into adult rats with unilateral lesions of the mesostriatal dopamine system. Immunohistochemica

Immature neural tissue grafts in Parkinson's disease

Intracerebral transplantation of immature neural tissue is a promising therapeutical approach that has the potential of restoring damaged neuronal circuitries and reversing functional deficits. The development of the technique as a human application has progressed the furthest in Parkinson's disease (PD), with the demonstration of significant longlasting functional improvements, in combination wit

Bilateral fetal mesencephalic grafting in two patients with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

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 gra

Transplantation of fetal dopamine neurons in Parkinson's disease : PET [18F]6-L-fluorodopa studies in two patients with putaminal implants

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 in

Transplantation of fetal dopamine neurons in Parkinson's disease : one-year clinical and neurophysiological observations in two patients with putaminal implants

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 pro

Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C : an observational cohort study

BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment w

Suicidal ideation in a European Huntington's disease population

BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's