Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats

Abstract

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.

“Optoanesthesia”: The Application of Transcranial Photobiomodulation to General Anesthesia

“…Correspondingly, Radwan et al [51] speculated that tPBM mimics benzodiazepine and barbiturates in its blocking effect on GABA B receptors (i.e. tPBM acts as a positive modulator of GABA B receptors [18]).…”

“…Amnesia elicited by etomidate is caused by the modulation of GABA type A (GABA A ) receptors in the hippocampus [52] [53] [54]. The study by Tsai et al [18] study indicated that tPBM can also modulate GABA A receptors by attenuating the noncompetitive antagonism of PTZ toward the GABA A receptor complex in postsynaptic principal cells.…”

“…The tPBM technique produced inhibitory effects in the cortex and hippocampus of normal healthy rats [25], while tPBM monotherapy attenuated seizures in peripubertal (808 nm wavelength) [17] [19] and adult rats (750 nm) [21]. In addition, tPBM (808 nm) add-on therapy combined with valproic acid attenuated pentylenetetrazole (PTZ)-induced seizures [18]. Further, Tsai [20] proposed the use of tPBM as an add-on therapy to be used with general anesthetics to treat pediatric refractory status epilepticus and super refractory status epilepticus.…”

Progress of Photobiomodulation for Parkinson’s Disease

“…Transcranial photobiomodulation (tPBM) is the application of PBM transcranially and noninvasively. tPBM has been applied to dementia including Alzheimer's disease, 23 traumatic brain injury, 24 stroke, 25 epilepsy, 17,21,26,27 PTSD, 28 anxiety and depression. 29 Corresponding to the two main mechanisms (α-synnuclein aggregation and mitochondrial dysfunction or failure of mitochondrial biogenesis) and a potential therapeutic target (microglial activation) in the pathogenesis of PD, PBM has correlated therapeutic effects against them respectively.…”

Photobiomodulation regulates adult neurogenesis in the hippocampus in a status epilepticus animal model

“…Photobiomodulation (PBM) therapy, previously known as low-level laser (light) therapy (LLLT) 10 , is a novel therapy for the treatment of various neurological disorders. Emerging evidence suggests that PBM protects neurons in epilepsy models, including an SE model [11][12][13][14] . In addition, PBM therapy causes hippocampal alterations 15 .…”