Prenatal alcohol exposure exacerbates acute sensorimotor deficits and impedes long-term behavioral recovery from the effects of an adult-onset cerebrovascular ischemic stroke.
Prenatal alcohol exposure exacerbates acute sensorimotor deficits and impedes long-term behavioral recovery from the effects of an adult-onset cerebrovascular ischemic stroke.
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DOI：
10.1111/acer.14952
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发表时间：
2022-12
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影响因子：
--
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产前酒精暴露（PAE）是发育障碍的一个重要风险因素，尽管其在整个生命周期中的健康后果知之甚少。在此，我们假设PAE的潜在脑和全身后果影响对成人发作的神经系统疾病（特别是脑血管缺血性卒中）的恢复能力。妊娠Sprague-Dawley大鼠在胎儿神经发生期间歇性暴露于乙醇。对成年（5个月）雄性和雌性PAE以及对照后代进行内皮素-1诱导的单侧大脑中动脉闭塞。在急性损伤阶段，评估了包括每搏输出量和神经、内分泌和肠道通透性标志物在内的结局。由于中风对人群的影响会在数月至数年内演变，因此我们还评估了中风后6个月内中年后代的海马和杏仁核依赖性记忆功能和社会互动偏好。产前酒精暴露并没有改变梗死体积，但显着增加神经功能缺损的两种性别，和受损的大脑半球间感觉运动整合的PAE女性。在PAE雄性动物中，IGF-1/IGFBP 3比值（生物可利用IGF-1的指标）显著降低，而细菌脂多糖（一种炎症原）的循环水平显著升高。在PAE女性中，循环IGF-1/IGFBP 3比值显著升高，雌二醇-17 b水平显著降低。肠脂肪酸结合蛋白（肠道通透性的替代标志物）在PAE雌性动物中也显著增加。在PAE雄性动物中观察到海马相关记忆和社会互动的长期缺陷，而在PAE雌性动物中观察到杏仁核依赖性记忆缺陷。PAE可对大脑健康产生不良影响，并降低常见成人发作性神经血管疾病（脑血管缺血性卒中）的弹性。本研究评估了产前酒精暴露（PAE）对5至12个月大的成年大鼠缺血性卒中（一种急性成人发病疾病）后神经行为和内分泌结局的影响。PAE后代表现出更大的神经和内分泌缺陷。在急性期，与非PAE对照组相比，PAE雌性动物在卒中后表现出感觉运动整合降低。PAE雄性动物在海马相关记忆和社会互动方面表现出长期缺陷，而PAE雌性动物在海马杏仁核依赖性学习方面表现出缺陷。总的来说，PAE降低了对常见成人发病神经系统疾病的恢复力。
Prenatal alcohol exposure (PAE) is a significant risk factor for developmental disability, although its health consequences across the lifespan are poorly understood. Here, we hypothesized that latent brain and systemic consequences of PAE influence resiliency to adult‐onset neurological disease, specifically, cerebrovascular ischemic stroke. Pregnant Sprague–Dawley rats were exposed episodically to ethanol during the fetal neurogenic period. Adult (5 months) male and female PAE and control offspring were subjected to endothelin‐1‐induced unilateral middle cerebral artery occlusion. In the acute injury phase outcomes including stroke volume and neurological, endocrine, and gut permeability markers were assessed. Because the effects of stroke in human populations evolve over months to years, we also assessed hippocampal‐ and amygdala‐dependent memory function and social interaction preference up to 6 months following a stroke, in middle‐aged offspring. Prenatal alcohol exposure did not alter infarct volume, but significantly increased neurological deficits in both sexes, and impaired interhemispheric sensorimotor integration in PAE females. The IGF‐1/IGFBP3 ratio, a measure of bioavailable IGF‐1, was significantly reduced, while circulating levels of bacterial lipopolysaccharide, an inflammagen, were significantly increased in PAE males. In PAE females, the circulating IGF‐1/IGFBP3 ratio was significantly increased and estradiol‐17b levels were significantly reduced. The intestinal fatty acid binding protein, a surrogate marker of gut permeability was also significantly increased in PAE females. Longer‐term deficits in hippocampal‐associated memory and social interactions were observed in PAE males, while deficits in amygdala‐dependent memory were observed in PAE females. PAE contributes to adverse effects on brain health and decreased resiliency in response to a common adult‐onset neurovascular disease, cerebrovascular ischemic stroke. This study assessed the impact of prenatal alcohol exposure (PAE) on neurobehavioral and endocrine outcomes in 5 to12 month‐old adult rats following ischemic stroke, an acute adult‐onset disease. PAE offspring exhibited greater neurological and endocrine deficits. PAE‐females exhibited decreased sensorimotor integration after stroke compared to non‐PAE controls during the acute phase. PAE males exhibited longer‐term deficits in hippocampal‐associated memory and social interactions, while PAE females showed deficits in hippocampal‐amygdala‐dependent learning. Collectively, PAE reduces resiliency to a common adult‐onset neurological disease.
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影响因子：
7.9
作者：
El-Hakim Y;Mani KK;Eldouh A;Pandey S;Grimaldo MT;Dabney A;Pilla R;Sohrabji F
通讯作者：
Sohrabji F
影响因子：
5.3
作者：
Manwani, Bharti;Liu, Fudong;Scranton, Victoria;Hammond, Matthew D.;Sansing, Lauren H.;McCullough, Louise D.
通讯作者：
McCullough, Louise D.
DOI：
10.1111/acer.13277
发表时间：
2017-01
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Bake S;Gardner R;Tingling JD;Miranda RC;Sohrabji F
通讯作者：
Sohrabji F
影响因子：
5.9
作者：
Denti, L;Annoni, V;Ceda, GP
通讯作者：
Ceda, GP
影响因子：
8
作者：
Hoyme, H. Eugene;Kalberg, Wendy O.;May, Philip A.
通讯作者：
May, Philip A.