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Updated: Nov 25, 2025
Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats
Published on: May 11, 2018
Noninvasive transcranial focal stimulation affects the convulsive seizure-induced P-glycoprotein expression and
Daniel Pérez-Pérez1, José Luis Castañeda-Cabral2, Sandra Orozco-Suárez3
1Plan of Combined Studies in Medicine (PECEM), Faculty of Medicine, UNAM, México City, Mexico.
Abstract:
Transcranial focal stimulation (TFS) is a noninvasive neuromodulation strategy that reduces seizure activity in different experimental models. Nevertheless, there is no information about the effects of TFS in the drug-resistant phenotype associated with P-glycoprotein (Pgp) overexpression. The present study focused on determining the effects of TFS on Pgp expression after an acute seizure induced by 3-mercaptopropionic acid (MPA). P-glycoprotein expression was analyzed by western blot in the cerebral cortex and hippocampus of rats receiving 5 min of TFS (300 Hz, 50 mA, 200 μs, biphasic charge-balanced squared pulses) using a tripolar concentric ring electrode (TCRE) prior to administration of a single dose of MPA. An acute administration of MPA induced Pgp overexpression in cortex (68 ± 13.4%, p < 0.05 vs the control group) and hippocampus (48.5 ± 14%, p < 0.05, vs the control group). This effect was avoided when TFS was applied prior to MPA. We also investigated if TFS augments the effects of phenytoin in an experimental model of drug-resistant seizures induced by repetitive MPA administration. Animals with MPA-induced drug-resistant seizures received TFS alone or associated with phenytoin (75 mg/kg, i.p.). TFS alone did not modify the expression of the drug-resistant seizures. However, TFS combined with phenytoin reduced seizure intensity, an effect associated with a lower prevalence of major seizures (50%, p = 0.03 vs phenytoin alone). Our experiments demonstrated that TFS avoids the Pgp overexpression induced after an acute convulsive seizure. In addition, TFS augments the phenytoin effects in an experimental model of drug-resistant seizures. According with these results, it is indicated that TFS may represent a new neuromodulatory strategy to revert the drug-resistant phenotype.
Insights
Transcranial focal stimulation (TFS) prevents P-glycoprotein (Pgp) overexpression after seizures. TFS also enhances phenytoin
Area of Science:
- Neuroscience
- Neuromodulation
- Epilepsy Research
Background:
- Transcranial focal stimulation (TFS) is a noninvasive neuromodulation technique with demonstrated efficacy in reducing seizure activity.
- The role of P-glycoprotein (Pgp) in drug-resistant epilepsy and the impact of TFS on Pgp expression remain largely unexplored.
- Drug resistance in epilepsy is a significant clinical challenge, often linked to altered drug efflux mechanisms like Pgp overexpression.
Purpose of the Study:
- To investigate the effects of TFS on P-glycoprotein (Pgp) expression following acute seizures induced by 3-mercaptopropionic acid (MPA).
- To evaluate whether TFS can augment the efficacy of phenytoin in an experimental model of drug-resistant seizures.
- To determine if TFS can potentially reverse the drug-resistant phenotype associated with Pgp overexpression.
Main Methods:
- Rats received 5 minutes of TFS (300 Hz, 50 mA, 200 μs pulses) using a tripolar concentric ring electrode before MPA administration.
- Pgp expression was quantified in the cerebral cortex and hippocampus via Western blot analysis.
- Drug-resistant seizure models were established using repetitive MPA administration, followed by treatment with TFS alone or in combination with phenytoin (75 mg/kg, i.p.).
Main Results:
- Acute MPA administration significantly increased Pgp expression in both the cortex (68%) and hippocampus (48.5%).
- Pre-treatment with TFS effectively prevented MPA-induced Pgp overexpression.
- TFS combined with phenytoin reduced seizure intensity and the prevalence of major seizures by 50% compared to phenytoin alone in the drug-resistant model.
Conclusions:
- Transcranial focal stimulation (TFS) effectively prevents P-glycoprotein (Pgp) overexpression induced by acute seizures.
- TFS potentiates the anticonvulsant effects of phenytoin in a model of drug-resistant epilepsy.
- TFS shows promise as a novel neuromodulatory strategy to combat the drug-resistant phenotype in epilepsy.
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