Presentation Title

Potential therapeutic role of inhibitory cell transplants for treating epilepsy after cerebrocortical stroke

Start Date

November 2016

End Date

November 2016

Location

HUB 367

Type of Presentation

Oral Talk

Abstract

Authors: Dale Tager, Stephanie Holden, Stefanie Makinson, Jeanne T. Paz

Stroke is the most common cause of seizures in the elderly population1 and 11.5% of patients with stroke are at risk of developing post-stroke (delayed) seizures within five years.2 The development of epilepsy after stroke may result from a maladaptive circuit recovery and an imbalance between excitation and inhibition resulting in a hyper-excitable peri-stroke cortex. Our project aimed to determine the potential anti-epileptic role of mouse embryonic stem cells in a cerebrocortical stroke rat model of epilepsy. The pluripotent stem cells, derived from the mouse medial ganglionic eminence (MGE), differentiate to inhibitory GABAergic interneurons. We hypothesized that the MGE transplants in the peri-stroke cortical area would enhance inhibition, reduce the hyperexcitability in the peri-stroke cortex, and thus prevent seizures. To test this hypothesis, we utilized the Rose Bengal (RB) ~40mg/kg photothrombosis stroke model to induce an ischemic cortical stroke in adult Sprague-Dawley rats. The rat cohorts include those with only stroke induction, those with stroke induction + MGE injection, and a Rose Bengal injection negative control group. After implanting the rats with EEG devices, we recorded EEG in freely behaving rats before and after an intraperitoneal injection of the proconvulsant Pentylenetetrazol (PTZ). The EEG data was used to compare the latency, frequency, and the number of epileptic spikes. We showed that a PTZ dose of 25mg/kg was subthreshold for seizure induction in control rats without stroke and induced seizures in rats with stroke but less in rats with stroke + MGE transplants (frequency and quantity of seizure activity, p<.05; among the MGE injected animals as compared to the stroke-only and RB-only control groups). Based on these preliminary data, we propose that inhibitory stem cell transplants could be a potential therapeutic approach to prevent epileptogenesis after cortical lesions.

1 National Stroke Association, 2 Myint et al 2008

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Nov 12th, 2:15 PM Nov 12th, 2:30 PM

Potential therapeutic role of inhibitory cell transplants for treating epilepsy after cerebrocortical stroke

HUB 367

Authors: Dale Tager, Stephanie Holden, Stefanie Makinson, Jeanne T. Paz

Stroke is the most common cause of seizures in the elderly population1 and 11.5% of patients with stroke are at risk of developing post-stroke (delayed) seizures within five years.2 The development of epilepsy after stroke may result from a maladaptive circuit recovery and an imbalance between excitation and inhibition resulting in a hyper-excitable peri-stroke cortex. Our project aimed to determine the potential anti-epileptic role of mouse embryonic stem cells in a cerebrocortical stroke rat model of epilepsy. The pluripotent stem cells, derived from the mouse medial ganglionic eminence (MGE), differentiate to inhibitory GABAergic interneurons. We hypothesized that the MGE transplants in the peri-stroke cortical area would enhance inhibition, reduce the hyperexcitability in the peri-stroke cortex, and thus prevent seizures. To test this hypothesis, we utilized the Rose Bengal (RB) ~40mg/kg photothrombosis stroke model to induce an ischemic cortical stroke in adult Sprague-Dawley rats. The rat cohorts include those with only stroke induction, those with stroke induction + MGE injection, and a Rose Bengal injection negative control group. After implanting the rats with EEG devices, we recorded EEG in freely behaving rats before and after an intraperitoneal injection of the proconvulsant Pentylenetetrazol (PTZ). The EEG data was used to compare the latency, frequency, and the number of epileptic spikes. We showed that a PTZ dose of 25mg/kg was subthreshold for seizure induction in control rats without stroke and induced seizures in rats with stroke but less in rats with stroke + MGE transplants (frequency and quantity of seizure activity, p<.05; among the MGE injected animals as compared to the stroke-only and RB-only control groups). Based on these preliminary data, we propose that inhibitory stem cell transplants could be a potential therapeutic approach to prevent epileptogenesis after cortical lesions.

1 National Stroke Association, 2 Myint et al 2008