Sewal Rakesh K, Modi Manish, Saikia Uma Nahar, Chakrabarti Amitava, Medhi Bikash
Department of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh, 160012, India.
Department of Pharmacology, Post Graduate Institute of Medical Education & Research, Chandigarh, 160012, India.
Epilepsy Res. 2017 Sep;135:176-186. doi: 10.1016/j.eplepsyres.2017.05.012. Epub 2017 Jun 15.
Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis.
Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted.
Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals.
Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon.
癫痫是一种以反复无诱因发作为特征的神经系统疾病。脓毒症是一种引发一系列炎症介质激增的病症。癫痫发作与非脑源性炎症之间的相互作用尚待探索。本研究旨在评估脂多糖（LPS）诱导的脓毒症实验模型中的癫痫易感性。
在Wistar大鼠中使用脂多糖诱导实验性脓毒症。将丙戊酸、地塞米松分别给予两组不同的动物，同时给予LPS。两组动物分别给予溶媒和LPS，不进行其他治疗。24小时后，通过最大电休克或戊四氮使动物发生癫痫发作。评估癫痫相关参数、氧化应激以及血清和脑样本中TNF-α、IL-6、IL-1β、ICAM-1、ICAM-2、VCAM-1、MMP-9水平。进行组织病理学和血脑屏障通透性研究。
丙戊酸治疗的动物癫痫发作减少。与单独LPS治疗组相比，地塞米松加丙戊酸治疗组的氧化应激降低。LPS治疗的动物中TNF-α、IL-6、IL-1β、ICAM-1、VCAM-1、MMP-9水平升高，而脑和血清中ICAM-2水平则相反。组织病理学结果证实动物成功建立了类似脓毒症的状态。LPS治疗的动物组血脑屏障通透性增加。
在类似脓毒症的炎症状态下癫痫易感性可能会升高，控制炎症状态可能会逆转这一现象。
