Abstract
Vigabatrin (VGB), a potent selective γ-aminobutyric acid transaminase (GABA-T) inhibitor, is an approved non-traditional anti-seizure drug for patients with intractable epilepsy. Nevertheless, its effect on epileptogenesis, and whether this effect is correlated with post-epileptogenic cognitive function remain unclear. Based on lithium-pilocarpine-induced seizure modeling, we evaluated the effect of VGB on epileptogenesis and neuronal damage following status epilepticus in Sprague–Dawley rats. Cognitive evaluations were performed with the aid of inhibitory avoidance testing. We found that VGB could interrupt epileptogenesis by reducing spontaneous recurrent seizures, hippocampal neuronal damage, and chronic mossy fiber sprouting. Nevertheless, VGB did not help with the retention of cognitive performance. Our findings suggest that further research into the role of VGB in epileptogenesis and the treatment of epilepsy in clinical practice is warranted.
Highlights
Life 2021, 11, 1213. https://doi.org/Vigabatrin (VGB) is a potent selective γ-aminobutyric acid transaminase (GABA-T)inhibitor with anti-seizure activity which has been approved as a monotherapy for infantile spasms and as an adjunctive therapy for refractory complex partial seizures [1,2,3].Earlier studies have demonstrated that it increases the levels of the inhibitory neurotransmitter GABA in a dose-dependent manner in the brains of mice and rats and in the cerebrospinal fluid of patients with epilepsy [4,5,6,7]
In addition to its GABAergic effect, we have recently found that VGB modulates neuronal calcium-activated potassium channels, suggesting that it is equipped with various mechanisms of action [8]
The mean number of daily spontaneous seizures exhibited per rat was calculated based on regular daily 4-h visual monitoring from 14 to 28 days after pilocarpine-induced status epilepticus
Summary
Life 2021, 11, 1213. https://doi.org/Vigabatrin (VGB) is a potent selective γ-aminobutyric acid transaminase (GABA-T)inhibitor with anti-seizure activity which has been approved as a monotherapy for infantile spasms and as an adjunctive therapy for refractory complex partial seizures [1,2,3].Earlier studies have demonstrated that it increases the levels of the inhibitory neurotransmitter GABA in a dose-dependent manner in the brains of mice and rats and in the cerebrospinal fluid of patients with epilepsy [4,5,6,7]. It has been demonstrated that VGB can abort acute focally evoked pilocarpine-induced seizures [9], pentylenetetrazole (PTZ)-induced seizures [10], and tetrodotoxin-induced infantile spasms [11]. It has exhibited variable anticonvulsant potential, it generally shows broad-spectrum anticonvulsant activity [4,12]. Another study has reported that VGB results in incomplete protection of the hippocampus, which is widely believed to be involved in temporal lobe seizure activity, and there is evidence that VGB has no influence on the generation of epilepsy [14], suggesting that the expression of the protein glutamic acid decarboxylase is independent of seizures. A recent study on a TSC/mTOR-dependent epilepsy mouse model has shown that VGB does not prevent epilepsy but significantly delays the onset of seizures and lowers their frequency [15]
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