RESUMEN
Cannabidiol (CBD), the main nonpsychotomimetic compound from Cannabis sativa, inhibits experimental seizures in animal models and alleviates certain types of intractable epilepsies in patients. Its pharmacological profile, however, is still uncertain. Here we tested the hypothesis that CBD anticonvulsant mechanisms are prevented by cannabinoid (CB1 and CB2) and vanilloid (TRPV1) receptor blockers. We also investigated its effects on electroencephalographic (EEG) activity and hippocampal cytokines in the pentylenetetrazole (PTZ) model. Pretreatment with CBD (60mg/kg) attenuated seizures induced by intraperitoneal, subcutaneous, and intravenous PTZ administration in mice. The effects were reversed by CB1, CB2, and TRPV1 selective antagonists (AM251, AM630, and SB366791, respectively). Additionally, CBD delayed seizure sensitization resulting from repeated PTZ administration (kindling). This cannabinoid also prevented PTZ-induced EEG activity and interleukin-6 increase in prefrontal cortex. In conclusion, the robust anticonvulsant effects of CBD may result from multiple pharmacological mechanisms, including facilitation of endocannabinoid signaling and TRPV1 mechanisms. These findings advance our understanding on CBD inhibition of seizures, EEG activity, and cytokine actions, with potential implications for the development of new treatments for certain epileptic syndromes.
Asunto(s)
Anticonvulsivantes/farmacología , Encéfalo , Cannabidiol/farmacología , Citocinas/metabolismo , Convulsiones/prevención & control , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Convulsivantes/farmacología , Modelos Animales de Enfermedad , Masculino , Ratones , Pentilenotetrazol/farmacología , Convulsiones/inducido químicamente , Convulsiones/metabolismo , Convulsiones/fisiopatologíaRESUMEN
The pathogenesis of autism spectrum disorder (ASD) is unknown, and the immune system has been appointed to play an important role. The interleukin 33 (IL-33), a member of the IL-1, may act as an alarmin. This study aimed to evaluate plasma levels of IL-33, sST2, and IL-1ß in 30 patients with ASD in comparison with 18 controls matched by gender, age and maternal age at childbirth. Patients did not differ from controls in IL-33, sST2, and IL-1ß plasma levels. Alarmin levels were not correlated with age, and neither was influenced by clinical parameters. Our results undermine the role of IL-33/ST2 in ASD.