Convulsive status epilepticus is the most common neurological emergency in children. Transcranial photobiomodulation (tPBM) reverses elevated rodent neurotransmitters after status epilepticus (SE) yet whether tPBM can attenuate seizure behaviors remains unknown. Here, we applied near‐infrared laser at wavelength 808 nm transcranially to peripubertal Sprague‐Dawley rats prior to pentylenetetrazole (PTZ) injection. Hematoxylin‐eosin, immunofluorescence (IF) staining with anti‐parvalbumin (PV) and terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) assay after IF staining was performed. Behaviorally, tPBM attenuated the mean seizure score and reduced the incidence of SE and mortality. Histochemically, tPBM reduced dark neurons in the cortex, hippocampus, thalamus and hypothalamus, lessened the apoptotic ratio of parvalbumin‐positive interneurons (PV‐INs) and alleviated the aberrant extent of PV‐positive unstained somata of PCs in the hippocampus. Conclusively, tPBM attenuated PTZ‐induced seizures, SE and mortality in peripubertal rats and reduced PTZ‐induced neuronal injury, apoptosis of PV‐INs and preserved PV positive perisomatic inhibitory network in the hippocampus.

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. Significance: Transcranial photobiomodulation (tPBM) at 808 nm attenuates pentylenetetrazole (PTZ)-induced seizures and convulsive status epilepticus (CSE) in peripubertal rats by protecting neurons from injury and parvalbumin-positive interneurons from apoptosis, and preserving the integrity of perisomatic inhibitory networks. However, the effects of tPBM on neuroinflammation, astrogliosis, and microgliosis in epileptic rat brains are unknown. Thus, further study to unveil these aspects is needed for understanding the phenomena of tPBM on pediatric CSE prevention. Aim: To evaluate the effects of tPBM on neuroinflammation, astrogliosis, and microgliosis in peripubertal rat hippocampus with PTZ-induced seizures and SE. Approach: An 808-nm diode laser was applied transcranially to peripubertal rats prior to PTZ injection. Immunofluorescence staining of neuron-specific enolase (NSE) was used as a marker of neuroinflammation, glial fibrillary acid protein (GFAP) for astrogliosis, ionized calcium-binding adapter molecule 1 (Iba-1) for microgliosis, and mitochondrial cytochrome c oxidase subunit 1 (MT-CO1) for confirming the involvement of cytochrome c oxidase (CCO). Results: tPBM significantly reduced NSE immunoreactivity in CA3 in PTZ-treated rats, GFAP immunoreactivity in CA1, and Iba-1 immunoreactivity in CA3. Enhancement of hippocampal MT-CO1 reflected that tPBM acted in CCO-dependent manner. Conclusions: tPBM (808) attenuated PTZ-induced seizures and SE by suppressing neuroinflammation, astrogliosis, and microgliosis in peripubertal rats.

Recently, the structure-function relationships between amphotericin B (AmB) and ergosterol have been solved using synthetic techniques that require a mycosamine-mediated direct binding interaction between AmB and ergosterol to form AmB ion channels. However, studies to directly probe the AmB-induced membrane permeability changes have not been conducted. In the present work, we investigate the following fundamental question: does AmB induce concentration- and time-dependent permeability changes across ergosterol-containing membranes? Herein, we employ fluorescent dyes of known average diameter to quantify the diameters of AmB ion channels. In addition, we take a single-particle tracking approach to define the intracellular microrheology in the absence and presence of AmB ion channels. Present results show that increasing AmB concentration tends to increase the preferential accumulation of AmB ion channels in the presence of the excess membrane-embedded ergosterol. We found that AmB induces time-dependent membrane permeability; increases approaching 50% in both the velocity fluctuations and diffusion coefficients of vesicles occur on the same time scale as the efflux of potassium ions (≅30min). Furthermore, we propose a two-dimensional, semi-regular tessellation model to geometrically assess the pore size of the AmB ion channels in response to the AmB dose. This approach offers one possibility for the design of AmB ion channels with tunable aqueous pore size, which could provide an opportunity to replace damaged membrane water channels of the aquaporin family in future applications.

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.

Our data revealed multiple SEPCs in normal-term neonates as a risk factor for neurobehavioral outcome, particularly in ADHD and ASD. Simultaneously, the utility of CUS examination as a health examination item for neonates was confirmed.

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