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耐力训练对海人酸诱导的自发性高血压大鼠癫痫持续状态后癫痫易感性、行为变化及神经元损伤的影响。

Effect of endurance training on seizure susceptibility, behavioral changes and neuronal damage after kainate-induced status epilepticus in spontaneously hypertensive rats.

作者信息

Tchekalarova J, Shishmanova M, Atanasova D, Stefanova M, Alova L, Lazarov N, Georgieva K

机构信息

Institute of Neurobiology, Bulgarian Academy of Sciences, Bulgaria.

Department of Pharmacology and Drug Toxicology, Medical University - Plovdiv, Bulgaria.

出版信息

Brain Res. 2015 Nov 2;1625:39-53. doi: 10.1016/j.brainres.2015.08.022. Epub 2015 Aug 28.

Abstract

The therapeutic efficacy of regular physical exercises in an animal model of epilepsy and depression comorbidity has been confirmed previously. In the present study, we examined the effects of endurance training on susceptibility to kainate (KA)-induced status epilepticus (SE), behavioral changes and neuronal damage in spontaneously hypertensive rats (SHRs). Male SHRs were randomly divided into two groups. One group was exercised on a treadmill with submaximal loading for four weeks and the other group was sedentary. Immediately after the training period, SE was evoked in half of the sedentary and trained rats by KA, while the other half of the two groups received saline. Basal systolic (SP), diastolic (DP) and mean arterial pressure (MAP) of all rats were measured at the beginning and at the end of the training period. Anxiety, memory and depression-like behaviour were evaluated a month after SE. The release of 5-HT in the hippocampus was measured using a liquid scintillation method and neuronal damage was analyzed by hematoxylin and eosin staining. SP and MAP of exercised SHRs decreased in comparison with the initial values. The increased resistance of SHRs to KA-induced SE was accompanied by an elongated latent seizure-free period, improved object recognition memory and antidepressant effect after the training program. While the anticonvulsant and positive behavioral effects of endurance training were accompanied by an increase of 5-HT release in the hippocampus, it did not exert neuroprotective activity. Our results indicate that prior exercise is an effective means to attenuate KA-induced seizures and comorbid behavioral changes in a model of hypertension and epilepsy suggesting a potential influence of hippocampal 5-HT on a comorbid depression. However, this beneficial impact does not prevent the development of epilepsy and concomitant brain damage.

摘要

先前已证实规律体育锻炼在癫痫与抑郁共病动物模型中的治疗效果。在本研究中,我们检测了耐力训练对自发性高血压大鼠(SHRs)对海藻酸(KA)诱导的癫痫持续状态(SE)的易感性、行为变化及神经元损伤的影响。雄性SHRs被随机分为两组。一组在跑步机上进行次最大负荷运动四周,另一组为久坐不动组。训练期结束后,立即对一半的久坐组和运动组大鼠注射KA诱发SE,而两组的另一半大鼠注射生理盐水。在训练期开始和结束时测量所有大鼠的基础收缩压(SP)、舒张压(DP)和平均动脉压(MAP)。在SE发作一个月后评估焦虑、记忆和抑郁样行为。采用液体闪烁法测量海马中5-羟色胺(5-HT)的释放,并通过苏木精和伊红染色分析神经元损伤。与初始值相比,运动的SHRs的SP和MAP降低。训练后,SHRs对KA诱导的SE的抵抗力增强,同时癫痫发作潜伏期延长,物体识别记忆改善且具有抗抑郁作用。虽然耐力训练的抗惊厥和积极行为效应伴随着海马中5-HT释放的增加,但它并未发挥神经保护活性。我们的结果表明,预先运动是减轻KA诱导的癫痫发作以及高血压和癫痫模型中共病行为变化的有效手段,提示海马5-HT对共病抑郁可能有潜在影响。然而,这种有益影响并不能预防癫痫的发展和伴随的脑损伤。

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