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Background
The process by which a brain insult elicits epilepsy is termed epileptogenesis and it is characterized by numerous molecular and functional alterations. Statins are first-line drugs for hypercholesterolemia and related diseases, and display neuroprotective properties in clinical and experimental studies. Considering the importance in developing therapeutic strategies to prevent or modify epileptogenesis, we aimed the present study to test the hypothesis that atorvastatin modifies seizure susceptibility of mice after status epilepticus (SE).Methods
Male and female C57BL/6 mice were submitted to the pilocarpine-induced SE and then treated with atorvastatin (10 or 100 mg/kg, once daily by gavage) for 14 days. At days 7 and 14 post SE we evaluated the susceptibility of mice to the convulsant effects of a low dose of PTZ (30 mg/kg). Cell loss in the hilus of dentate gyrus was evaluated by Giemsa staining.Results
Latencies to myoclonic jerks and to tonic-clonic seizures decreased between baseline (before SE) and days 7 and 14 after SE, confirming the development of seizure susceptibility. Atorvastatin protected against PTZ-induced tonic-clonic seizures in both sexes at day 14 post-SE. Protective effects were similar in both female and male mice, except that a high dose of atorvastatin was required for females (protection at 100 mg/kg versus 10 mg/kg in males). Giemsa staining did not reveal neuroprotective effects of atorvastatin.Conclusions
Atorvastatin treatment during epileptogenesis had slight beneficial effects on seizure susceptibility. These seem not related to neuroprotection. Further studies are needed to determine the disease-modifying potential of atorvastatin in epilepsy. 相似文献Areas covered: This review describes the mechanisms underlying the natural tolerance to food components and the development of an allergic response in sensitized individuals. Furthermore, therapeutic approaches proposed to manage these abnormal immunologic responses food are also presented and discussed.
Expert opinion: In the past, management of food allergies has consisted of the education of patients to avoid the ingestion of the culprit food and to initiate the therapy (e.g. self-injectable epinephrine) in case of accidental ingestion. In recent years, sublingual/oral immunotherapies based on the continuous administration of small amounts of the allergen have been developed. However, the long periods of time needed to obtain significant desensitization and the generation of adverse effects, limit their use. In order to solve these drawbacks, strategies to induce tolerance are being studied, such as the use of either adjuvant immunotherapy in order to facilitate the reversion of the Th2 response towards Th1 or the use of monoclonal antibodies to block the main immunogenic elements. 相似文献