Hashemi Paria, Roshan-Milani Shiva, Saboory Ehsan, Ebrahimi Loghman, Soltanineghad Maryam
Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran; Physiology Research Center, Department of Physiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Iran; Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.
Alcohol. 2016 Nov;56:51-57. doi: 10.1016/j.alcohol.2016.07.003. Epub 2016 Jul 28.
Prenatal exposure to stress or alcohol increases vulnerability of brain regions involved in neurobehavioral development and programs susceptibility to seizure. To examine how prenatal alcohol interferes with stress-sensitive seizures, corticosterone (COS) blood levels and pentylenetetrazol (PTZ)-induced seizure behaviors were investigated in rat pups, prenatally exposed to stress, alcohol, or both. Pregnant rats were exposed to stress and saline/alcohol on 17, 18, and 19 days of pregnancy and divided into four groups of control-saline (CS), control-alcohol (CA), restraint stress-saline (RS), and restraint stress-alcohol (RA). In CS/CA groups, rats received saline/alcohol (20%, 2 g/kg, intraperitoneally [i.p.]). In RS/RA groups, rats were exposed to restraint stress by being held immobile in a Plexiglas tube (twice/day, 1 h/session), and received saline/alcohol, simultaneously. After parturition, on postnatal days 6 and 15 (P6 & P15), blood samples were collected from the pups to determine COS level. On P15 and P25, PTZ (45 mg/kg) was injected into the rest of the pups and seizure behaviors were then recorded. COS levels increased in pups of the RS group but not in pups of the RA group. Both focal and tonic-clonic seizures were prevalent and severe in pups of the RS group, whereas only focal seizures were prominent in pups of the CA group. However, pups prenatally exposed to co-administration of alcohol and stress, unexpectedly, did not show additive epileptic effects. The failure of pups prenatally exposed to alcohol to show progressive or facilitatory epileptic responses to stressors, indicates decreased plasticity and adaptability, which may negatively affect HPA-axis performance or hippocampal structure/function.
产前暴露于应激或酒精会增加参与神经行为发育的脑区的易损性,并使癫痫易感性增强。为了研究产前酒精如何干扰应激敏感性癫痫发作,我们对产前暴露于应激、酒精或两者的大鼠幼崽的皮质酮(COS)血药浓度和戊四氮(PTZ)诱导的癫痫发作行为进行了研究。将怀孕大鼠在妊娠第17、18和19天暴露于应激和生理盐水/酒精中,并分为四组:对照-生理盐水组(CS)、对照-酒精组(CA)、束缚应激-生理盐水组(RS)和束缚应激-酒精组(RA)。在CS/CA组中,大鼠接受生理盐水/酒精(20%,2 g/kg,腹腔注射[i.p.])。在RS/RA组中,大鼠被固定在有机玻璃管中以暴露于束缚应激(每天两次,每次1小时),并同时接受生理盐水/酒精。分娩后,在出生后第6天和第15天(P6和P15),从幼崽中采集血样以测定COS水平。在P15和P25时,将PTZ(45 mg/kg)注射到其余幼崽体内,然后记录癫痫发作行为。RS组幼崽的COS水平升高,而RA组幼崽的COS水平未升高。RS组幼崽中局灶性和强直-阵挛性癫痫发作均普遍且严重,而CA组幼崽中仅局灶性癫痫发作明显。然而,产前同时暴露于酒精和应激的幼崽出人意料地未表现出叠加性癫痫效应。产前暴露于酒精的幼崽未能对应激源表现出渐进性或促进性癫痫反应,这表明可塑性和适应性降低,这可能会对下丘脑-垂体-肾上腺(HPA)轴功能或海马结构/功能产生负面影响。