Preliminary study of the behavioral effects of LBS-neuron implantation on seizure susceptibility following middle cerebral artery occlusion in the rats.

Neural transplantation is a promising treatment strategy that can restore the motor, sensory and cognitive functions in the rat middle cerebral artery occlusion (MCAO) model of stroke. In particular, neuronal cells derived from a human teratocarcinoma cell line, called hNT neurons or LBS neurons (clinical grade preparation), are effective in improving behavioral recovery after stroke. In the elderly, epilepsy is a common sequela of stroke, especially if the infarction involves cerebral cortex. However, the effect of implanting neural cells on seizure susceptibility in the MCAO model has not yet been determined. The purpose of this study was to determine the susceptibility to pentylenetetrazol (PTZ)-induced seizures in normal, MCAO-lesioned and MCAO-lesioned rats in which the LBS neurons were injected. Adult, male Sprague-Dawley rats were subjected to 60 min of MCAO using the intraluminal filament technique followed 3-4 weeks later by transplantation of 80,000 LBS-neurons into the ipsilateral cortex. Susceptibility to PTZ-induced seizures was tested 4-6 weeks post-transplant at doses of 35, 50 and 70 mg/kg, administered subcutaneously. Latency to the first lethal response, latency to first generalized seizure, duration of the first generalized seizure, and the number of generalized seizures in an hour post-PTZ treatment observation period was determined. Even thought there was a tendency for groups that underwent MCAO to be more susceptible to seizures, there were no statistically significant differences between the groups and no differences between MCAO alone and MCAO animals in which cells had been implanted. While grafted cells were identified in all but one injected animal, the results suggest that the grafts may not have been healthy either from immunological rejection or PTZ-induced injury. These results suggest that while placing cells within the cortex does not reduce seizure susceptibility, it also does not increase the incidence of seizures. Further investigations are warranted.