ArticleNeurobiology of disease2008
Benefits and risks of intranigral transplantation of GABA-producing cells subsequent to the establishment of kindling-induced seizures.
Article in Neurobiology of disease, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Sleep and Temporal Lobe Epilepsy - Associations, Mechanisms and Treatment Implications.Frontiers in human neuroscience · 2022Pooled it
- Human forebrain endothelial cell therapy for psychiatric disorders.Molecular psychiatry · 2021Article
- The Impacts of Surgery and Intracerebral Electrodes in C57BL/6J Mouse Kainate Model of Epileptogenesis: Seizure Threshold, Proteomics, and Cytokine Profiles.Frontiers in neurology · 2021Article
- Not Part of the Temporal Lobe, but Still of Importance? Substantia Nigra and Subthalamic Nucleus in Epilepsy.Frontiers in systems neuroscience · 2020Review
- Vascular Integrity and Signaling Determining Brain Development, Network Excitability, and Epileptogenesis.Frontiers in physiology · 2019Review
- GABA-ergic cell therapy for epilepsy: Advances, limitations and challenges.Neuroscience and biobehavioral reviews · 2016Review
- A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts.Molecular neurobiology · 2015Review
- Current prospects and challenges for epilepsy gene therapy.Experimental neurology · 2013Review
- Genetic strategies to investigate neuronal circuit properties using stem cell-derived neurons.Frontiers in cellular neuroscience · 2012Article
- Progress in cell grafting therapy for temporal lobe epilepsy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2011Review
- GABAergic neuronal precursor grafting: implications in brain regeneration and plasticity.Neural plasticity · 2011Review
- Recent advancements in stem cell and gene therapies for neurological disorders and intractable epilepsy.Neuropharmacology · 2010Review
- Transplantation of GABA-producing cells for seizure control in models of temporal lobe epilepsy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2009Review
- Intraventricular and intracerebral delivery of anti-epileptic drugs in the kindling model.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2009Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Neural transplantation has been investigated experimentally and clinically for the purpose of developing new treatment options for intractable epilepsy. In the present study we assessed the anticonvulsant efficacy and safety of bilateral allotransplantation of genetically engineered striatal GABAergic rat cell lines into the substantia nigra pars reticulata (SNr). Rats with previously-established seizures, induced by amygdala kindling, were used as a model of temporal lobe epilepsy. Three cell lines were transplanted: (1) immortalized GABAergic cells (M213-2O) derived from embryonic rat striatum; (2) M213-2O cells (CL4) transfected with human GAD67 cDNA to obtain higher GABA synthesis than the parent cell line; and (3) control cells (121-1I), also derived from embryonic rat striatum, but which did not show GAD expression. A second control group received injections of medium alone. Transplantation of M213-2O cells into the SNr of kindled rats resulted in significant but transient anticonvulsant effects. Neither control cells nor medium induced anticonvulsant effects. Strong tissue reactions were, however, induced in the host brain of kindled but not of non-kindled rats, and only in animals that received grafts of genetically modified CL4 cells. These tissue reactions included graft rejection, massive infiltration of inflammatory immune cells, and gliosis. The anticonvulsant effect of M213-2O cells emphasizes the feasibility of local manipulations of seizures by intranigral transplantation of GABA-producing cells. On the other hand, the present data suggest that kindling-induced activation of microglia in the SNr can enhance immune reactions to transplanted cells. In this case, under conditions of further immunological stimulation by CL4 cells, transfected with a human cDNA, substantial immune reactions occurred. Thus, it appears that the condition of the host brain and the production of foreign proteins by transplanted cells have to be considered in estimating the risks of rejection of transplants into the brain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.