Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats
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Published on: May 11, 2018
Chung-Min Tsai1,2, Shwu-Fen Chang1, Hsi Chang3,4
1Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Insights
Adding low-dose valproic acid (VPA) with transcranial photobiomodulation (tPBM) synergistically prevents seizures. However, high-dose VPA combined with tPBM worsened seizure severity in rats.
Area of Science:
- Neuroscience
- Biomedical Engineering
Background:
- Convulsive status epilepticus (CSE) prevention is crucial in pediatric epilepsy.
- Valproic acid (VPA) is an anticonvulsant but has dose-dependent hepatotoxicity.
- Transcranial photobiomodulation (tPBM) may allow for reduced VPA dosage.
Purpose of the Study:
- To investigate the synergistic effect of VPA and tPBM for CSE prevention.
- To determine if tPBM can enhance the efficacy of low-dose VPA.
- To evaluate the impact of combined VPA and tPBM on seizure severity.
Main Methods:
- Rats received pentylenetetrazole (PTZ) to induce seizures.
- VPA (100-400 mg/kg) was administered 30 minutes prior to PTZ.
- tPBM (808 nm wavelength) was applied transcranially 30 minutes after VPA.
- Seizure severity was assessed using the revised Racine scale.
Main Results:
- Low-dose VPA combined with tPBM reduced CSE incidence and delayed seizure onset.
- High-dose VPA with tPBM increased seizure stage and duration.
- tPBM offset the seizure-attenuating effect of high-dose VPA.
Conclusions:
- Low-dose VPA plus tPBM shows synergistic seizure prevention.
- High-dose VPA plus tPBM diminishes the therapeutic effect.
- This combination therapy warrants further investigation for optimized VPA dosing.
Background:
Convulsive status epilepticus (CSE) prevention is critical for pediatric patients with epilepsy. Immediate intervention before CSE reduce severity. Despite its wide usage as an anticonvulsant, valproic acid (VPA) results in harmful side effects such as dose-dependent hepatotoxicity. Hence, reducing VPA dosage to minimize side effects while maintaining its efficacy is necessary, and transcranial photobiomodulation (tPBM) add-on therapy could facilitate this. We recently demonstrated for the first time that tPBM at a wavelength of 808 nm attenuated CSE in peripubertal rats. However, the effects of VPA with the add-on therapy of tPBM prior to seizures have not yet been explored. This study investigated whether adding tPBM to VPA exerts synergistic effect for CSE prevention in peripubertal rats.
Methods:
A gallium-aluminum-arsenide laser (wavelength of 808 nm with an exposure duration of 100 s and irradiance of 1.333 W/cm2 at the target) was applied transcranially 30 min after VPA injection in Sprague Dawley rats. All the rats received 90 mg/kg of pentylenetetrazole (PTZ). Except for the saline (n = 3), tPBM + saline (n = 3), and PTZ group (n = 6), all the rats received a PTZ injection 30 min after VPA injection. The rats received add-on tPBM with PTZ immediately after tPBM. In the VPA + PTZ group, the rats received low-dose (100 mg/kg, n = 6), medium-dose (200 mg/kg, n = 6), and high-dose (400 mg/kg, n = 7) VPA. In the VPA + tPBM + PTZ group, the rats received low (100 mg/kg, n = 5), medium (200 mg/kg, n = 6), and high (400 mg/kg, n = 3) doses of VPA. Seizures were evaluated according to the revised Racine's scale in a non-blinded manner.
Results:
Adding tPBM to low-dose VPA reduced the incidence of severe status epilepticus and significantly delayed the latency to stage 2 seizures. However, adding tPBM to high-dose VPA increased the maximum seizure stage, prolonged the duration of stage 4-7 seizures, and shortened the latency to stage 6 seizures.
Conclusions:
Adding tPBM to low-dose VPA exerted a synergistic prevention effect on PTZ-induced seizures, whereas adding tPBM to high-dose VPA offset the attenuation effect.
