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Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-05-05 , DOI: 10.1007/s11064-020-03042-x
Mustafa Efendioglu 1 , Recep Basaran 2 , Metehan Akca 3 , Duygu Ceman 2 , Cumaali Demirtas 3 , Mehmet Yildirim 3
Affiliation  

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15 mg/kg, 30 min intervals, i.p.) 7 days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100 mg/kg), LEV (50 mg/kg), GBP (100 mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14 days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50 mg/kg LEV and 100 mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

中文翻译:

加巴喷丁和N-乙酰半胱氨酸联合治疗大鼠创伤后癫痫的疗效。

颅脑外伤(TBI)是世界范围内的主要公共卫生问题,与死亡率和发病率增加有关。创伤后癫痫(PTE)是TBI的后遗症之一。这项研究的目的是研究N-乙酰半胱氨酸(NAC)作为佐剂在戊烯四唑(PTZ)刺激的TTE刺激的男性Sprague-道利鼠。通过体重减轻法在雄性Sprague-Dawley大鼠中进行轻度TBI。通过在颅脑外伤后7天注射PTZ(30 + 15 + 15 mg / kg,间隔30分钟,腹腔注射)建立PTE模型。创伤后癫痫发作发展后,将大鼠用NAC(100 mg / kg),LEV(50 mg / kg),GBP(100 mg / kg),NAC + LEV和NAC + GBP腹膜内处理14天。通过视频脑电图记录对与PTE相关的癫痫发作进行评分。在旋转试验中也评估了动物的运动能力。50 mg / kg LEV和100 mg / kg GBP可减少与PTE相关的癫痫发作。仅LEV(p = 0.009),但GBP + NAC(p = 0.015)的给药对PTE相关的癫痫发作控制更为有效。但是,GBP + NAC的应用不利地影响了旋转脚架测试中的跌落潜伏期。就创伤相关的癫痫发作控制而言,使用预防性LEV和症状性LEV在统计学上无显着差异。单独使用LEV或将GBP与NAC结合使用,可在PTZ促进下对PTE进行更有效的癫痫发作控制。另一方面,预防性LEV的使用对创伤后癫痫发作的发展和控制没有任何额外的影响。50 mg / kg LEV和100 mg / kg GBP可减少与PTE相关的癫痫发作。仅LEV(p = 0.009),但GBP + NAC(p = 0.015)的给药对PTE相关的癫痫发作控制更为有效。但是,GBP + NAC的应用不利地影响了旋转脚架测试中的跌落潜伏期。就创伤相关的癫痫发作控制而言,使用预防性LEV和症状性LEV在统计学上没有显着差异。单独使用LEV或将GBP与NAC结合使用,可在PTZ促进下对PTE进行更有效的癫痫发作控制。另一方面,预防性LEV的使用对创伤后癫痫发作的发展和控制没有任何额外的影响。50 mg / kg LEV和100 mg / kg GBP可减少与PTE相关的癫痫发作。仅LEV(p = 0.009),但GBP + NAC(p = 0.015)的给药对PTE相关的癫痫发作控制更为有效。但是,GBP + NAC的应用不利地影响了旋转脚架测试中的跌落潜伏期。就创伤相关的癫痫发作控制而言,使用预防性LEV和症状性LEV在统计学上没有显着差异。单独使用LEV或将GBP与NAC结合使用,可通过PTZ促进PTE更有效地控制癫痫发作。另一方面,预防性LEV的使用对创伤后癫痫发作的发展和控制没有任何额外的影响。GBP + NAC的应用不利地影响了旋转脚架测试中的跌落潜伏期。就创伤相关的癫痫发作控制而言,使用预防性LEV和症状性LEV在统计学上无显着差异。单独使用LEV或将GBP与NAC结合使用,可在PTZ促进下对PTE进行更有效的癫痫发作控制。另一方面,预防性LEV的使用对创伤后癫痫发作的发展和控制没有任何额外的影响。GBP + NAC的应用不利地影响了旋转脚架测试中的跌落潜伏期。就创伤相关的癫痫发作控制而言,使用预防性LEV和症状性LEV在统计学上无显着差异。单独使用LEV或将GBP与NAC结合使用,可在PTZ促进下对PTE进行更有效的癫痫发作控制。另一方面,预防性LEV的使用对创伤后癫痫发作的发展和控制没有任何额外的影响。
更新日期:2020-05-05
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