Neuroprotective Effects of Gabapentin Against Cerebral Ischemia Reperfusion-Induced Neuronal Autophagic Injury via Regulation of the PI3K/Akt/mTOR Signaling Pathways

Yan, Bing Chun; Wang, Jie; Rui, Yanggang; Cao, Jianwen; Xu, Pei; Jiang, Dan; Zhu, Xiaolu; Won, Moo‐Ho; Bo, Ping; Su, Peiqing

doi:10.1093/jnen/nly119

Cited by 45 publications

(31 citation statements)

References 58 publications

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“…Furthermore, there is substantial evidence that the mammalian targets of rapamycin complex 1 (mTORC1) have an important effect on autophagy after ischemic stroke (Liu et al, 2016). Gabapentin (GBP) pretreatment has been shown to reduce brain IR injury by activating the PI3K/Akt/mTOR pathway, which exerted the neuroprotective effect via inhibiting the neurons autophagy associated with oxidative stress (Yan et al, 2019). Moreover, EA treatment could suppress hippocampal neuron apoptosis and improve neurological impairments in rats with cerebral palsy via regulating the PI3K/AKT signaling pathway .…”

Section: The Effect Of Ea Treatment On Autophagy and Apoptosis Of Neumentioning

confidence: 99%

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke

Wang

Zhang

Feng

et al. 2020

Front. Cell. Neurosci.

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Electroacupuncture (EA) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings. However, the underlying mechanism behind EA treatment for stroke remains unclear. Here, we aimed to evaluate whether EA treatment at the acupoints of Zusanli (ST36) and Quchi (LI11) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosis via the PI3K/AKT/mTOR signaling pathway. EA was performed at 24 h following brain ischemia/reperfusion (I/R) for 30 min per day for 3 days. Our results indicated that EA treatment significantly decreased neurological deficits and cerebral infarct volume in ischemic stroke rats. Also, EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 (CCAS3) at 72 h following I/R, as shown by a Western blot analysis. Furthermore, EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K, phosphorylation of mTOR, phosphorylation of AKT, P62 and LAMP1, hence mediating the autophagy level of the neurocyte, which was reversed by the PI3K inhibitor Dactolisib. In summary, our results indicate that the protective effects of EA treatment at points of Quchi (LI11) and Zusanli (ST36) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagy via activating the PI3K/AKT/mTOR signaling pathway.

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Section: The Effect Of Ea Treatment On Autophagy and Apoptosis Of Neumentioning

confidence: 99%

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke

Wang

Zhang

Feng

et al. 2020

Front. Cell. Neurosci.

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“…Gabapentin is a voltage-gated calcium channel (VGCC) inhibitor that indirectly affects the glutamate system. In cerebral ischemia-reperfusion mice, gabapentin treatment showed a neuroprotective effect and reduced neural injury in a dose-dependent manner [ 240 ]. In healthy populations, administration of a single dose of 50–400 mg of gabapentin promoted a subtle cognitive improvement [ 241 ].…”

Section: Novel Therapeutic Approachmentioning

confidence: 99%

Novel Therapeutic Approaches for Alzheimer’s Disease: An Updated Review

Lane

Lin

2021

IJMS

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease and accounts for most cases of dementia. The prevalence of AD has increased in the current rapidly aging society and contributes to a heavy burden on families and society. Despite the profound impact of AD, current treatments are unable to achieve satisfactory therapeutic effects or stop the progression of the disease. Finding novel treatments for AD has become urgent. In this paper, we reviewed novel therapeutic approaches in five categories: anti-amyloid therapy, anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents including N-methyl-D-aspartate (NMDA) receptor modulators, and brain stimulation. The trend of therapeutic development is shifting from a single pathological target to a more complex mechanism, such as the neuroinflammatory and neurodegenerative processes. While drug repositioning may accelerate pharmacological development, non-pharmacological interventions, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), also have the potential for clinical application. In the future, it is possible for physicians to choose appropriate interventions individually on the basis of precision medicine.

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“…The procedure is following that described above (28). The mice were killed with 10% chloral hydrate (Aladdin, Shanghai, China), and decapitation was performed immediately after full reperfusion (1 day).…”

Section: Ttc Staining and Quantifying Infarct Volumementioning

confidence: 99%

“…Western blot experiment was carried out on the basis of a procedure published before (28). The mice brains (n = 7 in each group) were cut into 400-µm thickness serially and transversely on a vibratome, and the hippocampus was carved with a scalpel.…”

Section: Western Blot Analysismentioning

confidence: 99%

A Network-Based Method for Mechanistic Investigation and Neuroprotective Effect on Post-treatment of Senkyunolid-H Against Cerebral Ischemic Stroke in Mouse

Zhang

Jiang

Liu³

et al. 2019

Front. Neurol.

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activation of PI3K/Akt/nuclear factor kappa B pathway, and the therapeutic effect of SEH was obviously inhibited by 10 µM LY294002. In summary, these results suggested that SEH carries a therapeutic potential in CIS involving multiple targets and pathways, and the most crucial mechanism might be through the activation of PI3K/Akt/nuclear factor kappa B (NF-κB) signaling pathway to inhibit inflammatory factor releases and increase the antiapoptosis capacity. Our study furnishes the future traditional Chinese medicine research with a network pharmacology framework.

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Neuroprotective Effects of Gabapentin Against Cerebral Ischemia Reperfusion-Induced Neuronal Autophagic Injury via Regulation of the PI3K/Akt/mTOR Signaling Pathways

Cited by 45 publications

References 58 publications

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke

Electroacupuncture Inhibits Neuronal Autophagy and Apoptosis via the PI3K/AKT Pathway Following Ischemic Stroke

Novel Therapeutic Approaches for Alzheimer’s Disease: An Updated Review

A Network-Based Method for Mechanistic Investigation and Neuroprotective Effect on Post-treatment of Senkyunolid-H Against Cerebral Ischemic Stroke in Mouse

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