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The causes of death of transplanted neurons are not known in detail, but apoptotic mechanisms involving caspase activation are likely to play a role. We examined whether overexpression of the anti-apoptotic protein Bcl-2 may enhance the survival of dopaminergic [tyrosine hydroxylase (TH)-immunoreactive] grafted neurons. For this purpose, we prepared cells from embryonic day 13 ventral mesencephalo
Transplantation of porcine embryonic brain cells, including dopaminergic neurons, from ventral mesencephalon (VM) is considered a potential treatment for patients with Parkinson's disease. In the present study, we characterized the distribution among VM cells of the major porcine endothelial xenoantigen, the Galalpha1,3Gal epitope, and evaluated the cytotoxic effect of anti-Galalpha1,3Gal antibody
Embryonic neural tissue obtained from other species has been considered as a donor tissue source in repair strategies for human neurodegenerative disorders. The neuro- and immunobiology of distantly related species combinations, discordant xenografts, need to be characterised. For this purpose, a small animal model would be an important research tool. Adult guinea-pigs, and adult rats as controls,
In 1992 the Core Assessment Program for Intracerebral Transplantations (CAPIT) was published providing the minimal requirements for a common patient evaluation protocol. Despite the intent, the program was thought to be too laborious to carry out in large scale trials, and it also lacked evaluations of cognitive functions and quality of life. Moreover, the CAPIT was designed for neural transplanta
Neural tissue grafting can be highly effective and constitutes a potentially curative approach for progressive neurodegenerative disorders such as PD. Virtually all signs and symptoms of PD have been shown to improve after grafting but not necessarily simultaneously in one patient. Several technical aspects require improvement before widespread use of neural tissue implants can be recommended. The
It has been suggested that inflammation related to intracerebral transplantation surgery can affect the survival of intrastriatal neural allografts. To test this hypothesis, we transplanted dissociated embryonic mesencephalic tissue from one of two rat strains, Lewis (allogeneic grafts) or Sprague-Dawley (syngeneic grafts), to the striatum of Sprague-Dawley rats. The target striatum was either int
The present study was designed to address two questions. First, can an intrastriatal neural allograft exhibit long-term survival (18 weeks) if the host is immunized by an orthotopic skin graft 6 weeks after neural transplantation (the 6w-Long group)? Second, can an intrastriatal neural allograft survive when the host is challenged by an orthotopic skin allograft either simultaneously (Sim) with th
To address the importance of antigen-presenting cells for the survival of intracerebral neural allografts, allogeneic spleen cells were added to the graft tissue before transplantation. Dissociated embryonic, dopamine-rich mesencephalic and adult spleen tissues were prepared from either inbred Lewis or Sprague-Dawley rats. A mixture of neural and spleen cells was sterotaxically transplanted into t
Grafts of striatal tissue comprise two different types of tissue: regions with (P-zones) and without (NP-zones) neurons that express markers characteristic of the striatum, such as dopamine- and cyclic AMP-regulated phosphoprotein with a mol. wt of 32,000 (DARPP-32). It remains unclear whether P-zones alone play a crucial role in functional effects of striatal grafts in an animal model of Huntingt
It has been suggested that oxidative stress plays an important role in mediating excitotoxic neuronal death. We have therefore investigated the protective effects of antioxidants against excitotoxic injury in the rat on striatal neurons both in vitro and in vivo. In the first part of the study, we determined whether two different types of antioxidants, the spin trapping agent, alpha-phenyl-tert-bu
We studied the effects of high-dose methylprednisolone on the survival of intrastriatal neural xenografts and the host responses against them. Dissociated mesencephalic tissue from inbred mouse (CBA-strain) embryos was transplanted to the intact striatum of adult Sprague-Dawley rats. The rats received either daily injections of methylprednisolone (30 mg/kg), or cyclosporin A (10 mg/kg), or no immu
A high survival rate of grafted dopamine neurons is crucial for reversing neurological deficits following brain tissue transplantation in Parkinson's disease. For unknown reasons the survival rate of transplanted dopamine neurons is only around 10% in experimental animals. The hypothesis that oxidative stress causes the loss of transplanted neurons was tested by grafting neurons from transgenic mi
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
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
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
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
