Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway

Lotfy, Dina M.; Safar, Marwa M.; Mohamed, Seham H.; Kenawy, Sanaa A.

doi:10.1016/j.lfs.2018.10.007

Cited by 6 publications

(2 citation statements)

References 37 publications

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“…Consequently, the expression of REST/NRSF target genes was also similar in both treatment groups, and minor differences did not reach statistical significance, suggesting that the mild neuroprotective effects of VPA after TBI were not mediated via the de-repression of the REST/NRSF complex. Previous data indeed suggest that autophagy and the Nrf2/ARE pathway may be more relevant for VPA-mediated protection in this context [25], and further mechanisms of actions of VPA may contribute to the overall outcome including the potentiation of gamma-aminobutyric acid (GABA) signaling via the modulation of GABA metabolism [60] and activation of mTOR signaling [61].…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines

Hummel,

Dorochow,

Zander

et al. 2024

Cells

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The histone deacetylase inhibitor (HDACi) valproic acid (VPA) has neuroprotective and anti-inflammatory effects in experimental traumatic brain injury (TBI), which have been partially attributed to the epigenetic disinhibition of the transcription repressor RE1-Silencing Transcription Factor/Neuron-Restrictive Silencer Factor (REST/NRSF). Additionally, VPA changes post-traumatic brain injury (TBI) brain metabolism to create a neuroprotective environment. To address the interconnection of neuroprotection, metabolism, inflammation and REST/NRSF after TBI, we subjected C57BL/6N mice to experimental TBI and intraperitoneal VPA administration or vehicle solution at 15 min, 1, 2, and 3 days post-injury (dpi). At 7 dpi, TBI-induced an up-regulation of REST/NRSF gene expression and HDACi function of VPA on histone H3 acetylation were confirmed. Neurological deficits, brain lesion size, blood–brain barrier permeability, or astrogliosis were not affected, and REST/NRSF target genes were only marginally influenced by VPA. However, VPA attenuated structural damage in the hippocampus, microgliosis and expression of the pro-inflammatory marker genes. Analyses of plasma lipidomic and polar metabolomic patterns revealed that VPA treatment increased lysophosphatidylcholines (LPCs), which were inversely associated with interleukin 1 beta (Il1b) and tumor necrosis factor (Tnf) gene expression in the brain. The results show that VPA has mild neuroprotective and anti-inflammatory effects likely originating from favorable systemic metabolic changes resulting in increased plasma LPCs that are known to be actively taken up by the brain and function as carriers for neuroprotective polyunsaturated fatty acids.

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Section: Discussionmentioning

confidence: 99%

Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines

Hummel,

Dorochow,

Zander

et al. 2024

Cells

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“…The benefits of polytherapy (combination or add-on therapy) using tPBM and AEDs, such as VPA, remained unknown. Combination therapy for seizures that administered AEDs and other electromagnetic waves was first demonstrated by Lotfy et al who reported that VPA combined with whole-body low-dose gamma irradiation (LDR) exerted synergistic effects on PTZ-induced seizures in rats [ 64 ]. However, the adverse side effects of LDR, such as DNA mutation, are concerning, particularly in the context of treating children [ 65 ].…”

Section: Introductionmentioning

confidence: 99%

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

Tsai

Chang

2022

BMC Complement Med Ther

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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.

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Neuroprotective effect of Wogonin on Rat's brain exposed to gamma irradiation

Wang

Sreeharsha

et al. 2020

Journal of Photochemistry and Photobiology B: Biology

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Effect of valproic acid alone or combined with low dose gamma irradiation in modulating PTZ-induced convulsions in rats involving AKT/m-TOR pathway

Cited by 6 publications

References 37 publications

Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines

Valproic Acid Treatment after Traumatic Brain Injury in Mice Alleviates Neuronal Death and Inflammation in Association with Increased Plasma Lysophosphatidylcholines

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

Neuroprotective effect of Wogonin on Rat's brain exposed to gamma irradiation

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