Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

Nociceptin/orphanin and substance P concentrations in critically III patients with sepsis

Sepsis is estimated to affect eighteen million people worldwide each year and kill 1, 400 people each day. Sepsis affects about 700, 000 people annually in the United States alone. The neuropeptide nociceptin/orphanin [N/OFQ] and substance P [SP] are two neuropathies involved in control of pain pathways. They have been implicated in neural, immune, inflammatory process and cardiovascular system function. In this study we evaluated the N/OFQ plasma levels and SP serum levels in critically ill patients with severe sepsis. Blood samples were collected from twenty patients with the diagnosis of severe sepsis. They were admitted in the intensive care unit. Plasma N/OFQ concentrations were determined by radio immunoassay. SP in the serum was evaluated by enzyme-linked immunoassay. Samples were collected within twenty four hours of diagnosis of sepsis in all cases. Another set of samples were collected in nine patients before death [non-survivors] and eleven patient upon recovery from severe sepsis [survivors]. The results revealed significant high levels of N/OFQ in patients with severe sepsis [non-survivors] compared with the other group of survivors [p<0.031]. The levels were significantly high in cases near death [non-survivors] compared to the survivors [p<0.012] near recovery. SP levels were significantly high in sepsis non-survivors compared to survivors [p<0.001] and significantly elevated in non-survivors before death compared to survivors near recovery [p<0.001]. Plasma N/OFQ and Serum SP, concentrations were increased in critically ill patients with sepsis and more elevated in patients who subsequently died. These two neuropeptides represent an important item for further studies to confirm their prognostic value as predictive indicators of lethal outcome or recovery. Also this study invites more work to determine the neuroendocrine system critical role in the pathogenesis of sepsis

effect of breast feeding on plasma cholecystokinin in neonates

this prospective study was conducted to evaluate the effect of breast-feeding on cholecystokinin in neonates. this study was conducted in King Abdul-Aziz University Hospital. Plasma concentration of cholecystokinin [CCK] was estimated in 41 neonates [19 boys, 22 girls]. The study was done in the neonates on the third day after delivery. Serum CCK was estimated by radioimmunoassy. it was found that CCK rises immediately after breast feeding and declines 10 minutes later. CCK rises immediately after breast-feeding and declines 10 minutes later