Evaluation of the ameliorative effects of oral administration of metformin on epileptogenesis in the temporal lobe epilepsy model in rats

Vazifehkhah, Somayeh; Ali, Mohammad Khanizadeh; Babae, Javad Fahanik; Hashemi, Paria; Alireza, Moein Sadat; Nikbakht, Farnaz

doi:10.1016/j.lfs.2020.118066

Cited by 14 publications

(3 citation statements)

References 47 publications

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“…The sclerotic hippocampus has an abnormal neuronal activity initiation region, which spreads to the frontal cortex [21].Some projections from the ventral hippocampus and ventral cingulate to the NAcSh, while efferent fibers mainly project to the VTA and frontal cortex [22,23]. Stereotactic ablations of the NAcSh have been applied to treat drug addiction, and refractory psychiatric disorders have also been identified as effective targets [24,25].When treatment of drug refractory epilepsy (DRE) with neuropsychological disorders, seizures were significantly alleviated [6,26]. In some studies, in which the NAc was electrically stimulated in a rat model combined with pilocarpine to initiate seizures, highfrequency stimulation of the NAc significantly prolonged the incubation period of seizures and inhibited their severity [13,27].…”

Section: Discussionmentioning

confidence: 99%

Nucleus accumbens shell lesions alleviate symptoms in kainic acid-induced epileptic rats

Xue

2023

Preprint

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Epilepsy is a recurrent neurological disease caused by hypersynchronous firing of neurons in the brain. Neuronal apoptosis, microgliosis, or astrogliosis in hippocampus are considered to be important features of temporal lobe epilepsy. As an important part of the ventral striatum, the nucleus accumbens is closely connected to the hippocampus. As the findings of the reviewed articles indicated, the nuleus accumbens is divided into the shell and the core. The nucleus accumbens shell is a relevant brain region to process reward-related and motivated behaviours, emotional process and social information. Nucleus accumbens shell has a good application effect in the field of drug addiction and mania. Our previous studies have shown that the nucleus accumbens shows abnormal excitation after seizures. In our previous experiments, the number of seizures decreased when this excitation was disrupted. However, the mechanisms of action of Nucleus accumbens shell lesions remain unclear. In this paper, we explored the hippocampal changes inhibited by nucleus accumbens lesions on the basis of the kainic acid animal model of epilepsy. We explored the anti-epileptic effect and mechanism of action of electrical lesions in nucleus accumbens, and found that the mechanism may be to reduce the toxic effects caused by the proliferation of astrocytes and microglia in the hippocampus. It can also inhibit the reduction of neurons and thus play a role in controlling seizures. These results suggest that the nucleus accumbens plays an important role in inhibiting seizures.

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Section: Discussionmentioning

confidence: 99%

Nucleus accumbens shell lesions alleviate symptoms in kainic acid-induced epileptic rats

Xue

2023

Preprint

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“…Mossy fiber sprouting is considered a major feature of aberrant tissue remodeling after neural loss caused by epilepsy in both humans and animal models [ 23 , 24 ]. Recent studies also suggest that reduced mossy fiber sprouting is a potential mechanism of action of several anti-epilepsy therapies, which may reduce hippocampal neuronal injury [ 25 – 27 ]. Importantly, we found new evidence for a lower Timm score in NBP-treated epilepsy rats, which is likely associated with the reduced frequency of seizure onset.…”

Section: Discussionmentioning

confidence: 99%

DL-3-n-butylphthalide promotes hippocampal neurogenesis and reduces mossy fiber sprouting in chronic temporal lobe epilepsy rats

Zhao

Liu

Shi³

et al. 2022

BMC Neurol

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Background A decrease in hippocampal neurogenesis is considered an important cause of cognitive impairment, while changes in mossy fiber sprouting are closely related to development of spontaneous recurrent seizures in chronic temporal lobe epilepsy (TLE). Racemic l-3-n-butylphthalide (DL-NBP) can alleviate cognitive impairment in ischemic stroke and Alzheimer’s disease by promoting neurogenesis. DL-NBP treatment can also improve cognitive function and reduce seizure incidence in chronic epileptic mice. However, the mechanisms of action of DL-NBP remain unclear. The aim of the present study was to examine the effects of DL-NBP on mossy fiber sprouting, hippocampal neurogenesis, spontaneous epileptic seizures, and cognitive functioning in the chronic phase of TLE. Methods Nissl staining was used to evaluate hippocampal injury, while immunofluorescent staining was used to analyze hippocampal neurogenesis. The duration of spontaneous seizures was measured by electroencephalography. The Morris water maze was used to evaluate cognitive function. Timm staining was used to assess mossy fiber sprouting. Results TLE animals showed reduced proliferation of newborn neurons, cognitive dysfunction, and spontaneous seizures. Treatment with DL-NBP after TLE increased the proliferation and survival of newborn neurons in the dentate gyrus, reversed the neural loss in the hippocampus, alleviated cognitive impairments, and decreased mossy fiber sprouting and long-term spontaneous seizure activity. Conclusions We provided pathophysiological and morphological evidence that DL-NBP might be a useful therapeutic for the treatment of TLE.

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“…AMPK activation by metformin also exhibits an anti-inflammatory effect in kainateinduced status epilepticus by inhibiting IL-1beta production and reducing the expression of glial fibrillary acidic protein (GFAP) and S100beta markers of astrogliosis, as well as by increasing secretion of the anti-inflammatory cytokine IL-10 [71]. In this model, metformin exerted a neuroprotective role against the kainate-induced epileptogenic process by preventing neuronal cell death, aberrant neurogenesis, and mossy fiber sprouting [72].…”

Section: Epilepsymentioning

confidence: 93%

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

Sanz

Serratosa

Sánchez

2021

IJMS

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Metformin is a drug in the family of biguanide compounds that is widely used in the treatment of type 2 diabetes (T2D). Interestingly, the therapeutic potential of metformin expands its prescribed use as an anti-diabetic drug. In this sense, it has been described that metformin administration has beneficial effects on different neurological conditions. In this work, we review the beneficial effects of this drug as a neuroprotective agent in different neurological diseases, with a special focus on epileptic disorders and Lafora disease, a particular type of progressive myoclonus epilepsy. In addition, we review the different proposed mechanisms of action of metformin to understand its function at the neurological level.

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Evaluation of the ameliorative effects of oral administration of metformin on epileptogenesis in the temporal lobe epilepsy model in rats

Cited by 14 publications

References 47 publications

Nucleus accumbens shell lesions alleviate symptoms in kainic acid-induced epileptic rats

Nucleus accumbens shell lesions alleviate symptoms in kainic acid-induced epileptic rats

DL-3-n-butylphthalide promotes hippocampal neurogenesis and reduces mossy fiber sprouting in chronic temporal lobe epilepsy rats

Beneficial Effects of Metformin on the Central Nervous System, with a Focus on Epilepsy and Lafora Disease

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