Eslami Mansoureh, Ghanbari Elham, Sayyah Mohammad, Etemadi Fatemeh, Choopani Samira, Soleimani Mansoureh, Amiri Zohreh, Hadjighassem Mahmoudreza
a Department of Physiology and Pharmacology , Pasteur Institute of Iran , Tehran , Iran.
b Department of Physiology , Paramedical Faculty, Shaheed Beheshti University of Medical Sciences , Tehran , Iran.
Neurol Res. 2016 Mar;38(3):269-74. doi: 10.1179/1743132815Y.0000000086. Epub 2016 Apr 19.
Traumatic brain injury (TBI) is a well-known cause of symptomatic epilepsy. In animal models of post-traumatic epilepsy (PTE), progression of trauma to epilepsy takes several weeks to months. Although this long process is similar to clinical PTE, it is costly and laborious. We used a combination of TBI and kindling as an accelerated animal model to develop epilepsy in much shorter period compared to that occurring in PTE.
Traumatic brain injury was exerted to parieto-temporal cortex of anaesthetised rats by controlled cortical impact (CCI, 5 mm round tip, 4.5 mm/seconds velocity and 150 ms duration). Chemical kindling started 24 hours after CCI by intraperitoneal injection of 30 mg/kg pentylenetetrazole (PTZ) every other day until manifestation of three consecutive generalised seizures. Rapid electrical kindling of the amygdala began 1 week after TBI by exertion of 12 daily threshold stimuli (50 Hz mono-phasic square-wave stimulus of 1 ms per wave for 3 seconds) with 5 minutes interval between each stimulation until the rats became kindled.
Controlled cortical impact injury accelerated rate of both chemical and electrical kindling. Number of PTZ injections required for acquisition of generalised seizures decreased from 13.1 ± 1.6 in sham-operated animals to 7.1 ± 0.3 in traumatic rats (p < 0.05). The required number of stimuli to elicit electrically kindled focal and generalised seizures decreased from 24.0 ± 3.9 and 80 ± 6.5 in sham-operated animals to 6.6 ± 0.9 and 53 ± 6.5 in traumatic rats (p < 0.01), respectively.
Unlike the animal models of PTE in which recurrent seizures occur spontaneously after TBI, in our study, epilepsy is elicited by kindling stimulations.
Traumatic brain injury facilitates acquisition of epilepsy in both chemical and electrical kindling models. Combination of trauma and kindling can be considered as an inexpensive and time-saving animal model in PTE studies.
创伤性脑损伤（TBI）是症状性癫痫的一个众所周知的病因。在创伤后癫痫（PTE）的动物模型中，从创伤发展到癫痫需要数周至数月的时间。尽管这个漫长的过程与临床PTE相似，但成本高昂且费力。我们采用TBI和点燃相结合的方法作为一种加速动物模型，与PTE模型相比，能在更短的时间内诱发癫痫。
通过控制性皮质撞击（CCI，圆头5毫米，速度4.5毫米/秒，持续时间150毫秒）对麻醉大鼠的颞顶叶皮质施加创伤性脑损伤。化学点燃在CCI后24小时开始，每隔一天腹腔注射30毫克/千克戊四氮（PTZ），直至出现连续三次全身性癫痫发作。TBI后1周开始对杏仁核进行快速电点燃，每天施加12次阈刺激（50赫兹单相方波刺激，每波1毫秒，持续3秒），每次刺激间隔5分钟，直至大鼠被点燃。
控制性皮质撞击损伤加快了化学和电点燃的速度。获得全身性癫痫发作所需的PTZ注射次数从假手术动物的13.1±1.6次减少到创伤大鼠的7.1±0.3次（p<0.05）。诱发电点燃性局灶性和全身性癫痫发作所需的刺激次数分别从假手术动物的24.0±3.9次和80±6.5次减少到创伤大鼠的6.6±0.9次和53±6.5次（p<0.01）。
与TBI后自发出现复发性癫痫发作的PTE动物模型不同，在我们的研究中，癫痫是由点燃刺激诱发的。
创伤性脑损伤在化学和电点燃模型中都促进了癫痫的获得。创伤和点燃相结合可被视为PTE研究中一种廉价且省时的动物模型。
