Transplantation of M213-2O Cells with Enhanced GAD67 Expression into the Inferior Colliculus Alters Audiogenic Seizures

Intranigral transplants of a GABAergic cell line produce long-term alleviation of established motor seizures

“…The incidence of stage III, IV, and V seizures, defined according to Racine's observations [38], was quantified during the light phase of the daily cycle for 6-8 h/week, totaling 24-32 h/month. Between transplantation and euthanasia, each animal was observed 72-96 h.…”

“…three weeks. Ross and coworkers [38] found that cells engineered to express human GAD67 decreased audiogenic seizures for two weeks. Thompson [42] found that transplantation of cells engineered to express GAD65 into the dentate gyrus increased the threshold and reduced the duration of the after discharge induced by granule cell stimulation and also slowed the appearance of stage V seizures after stimulation of the entorhinal cortex.…”

“…Second, GABA production was enhanced by introducing the GAD67 gene, the presumed non-synaptic GAD isoform, using an episomal Epstein-Barr virus based plasmid. These cells were found to produce relatively high levels of GABA [8] and to suppress audiogenic seizures on a short-term basis [38] and kainic acid-induced seizures eight weeks after transplantation [5]. In this study we sought to determine whether grafts of M213-2O/Cl4 cells could suppress established kainic acid-induced behavioral seizures on a long-term basis.…”

Evaluation of plasmid permanence in transfected cells after transplantation into the rat brain

“…This approach is illustrated using the cell line M213-2O CL-4 engineered with human GAD 67 (hGAD 67 ), which produces GABA in larger amounts than the parent cell line without hGAD 67 . These cells have been transplanted previously to evaluate their antiepileptogenic and anticonvulsant effects in seizure models; however, the mechanism underlying these effects remains unclear (Castillo et al, 2006(Castillo et al, , 2008Ross et al, 2002). The methodology described in this article may be readily applicable for quantification of plasmid present at low concentration in other transplantation models.…”

The Role of Cell Therapy in the Treatment of Epilepsy: Lessons from Animal Models and Clinical Trials

“…From the clones obtained, one was selected, the M213-2O CL-4 that synthesizes and releases significantly more GABA than the parent cell line (Conejero-Goldberg et al, 2000), reuptakes GABA, responds to glutamate, presents calcium transients, and releases the neurotransmitter in a calcium-dependent manner (Mejia-Toiber et al, 2010). This cell line when transplanted into the inferior colliculus increases the latency for audiogenic seizures (Ross, et al, 2002); it increases the latency for tonic-clonic seizures induced by kainic acid, and decreases their severity when transplanted into the SNr (Castillo et al, 2006) (Table 2). In a more recent www.intechopen.com study, it was found that intranigral transplants of this GABAergic cell line decrease the percentage of rats showing spontaneous seizures induced by kainic acid, at 4 and 12 weeks after transplantation into the SNr (Castillo et al, 2008) (Table 2).…”