恒河猴慢性颞叶癫痫模型的构建

Establishment of a rhesus monkey model of chronic temporal lobe epilepsy

目的建立一种灵长类慢性颞叶癫痫（TLE）模型，为致痫网络及相关研究提供实验基础。方法8只成年雄性恒河猴按照随机数字表法分为海人酸（KA）注射组（n=6），盐水注射组（n=2）。通过脑立体定向技术靶向右侧杏仁核植入微导管并连接皮下储液囊．视频脑电图监测下经皮穿刺储液囊重复注射KA或生理盐水，观察注射即刻及首次放电后至少6个月内2组恒河猴发作间期癫痫样放电（IEDs）、发作期放电情况及行为学表现。结果KA注射组6只恒河猴经过2-4次KA注射后均记录到典型的IEDs，表现为定位于右侧颞区的局灶性棘波放电：其中4只捕捉到发作期放电，表现为起源于右侧颞区并迅速向全脑扩散的放电模式，发作时恒河猴表现为突然停止活动，愣神或茫然四顾，无明显肢体抽搐表现。而盐水注射组在包括慢性期的整个实验过程中，均未记录到典型的癫痫样放电及发作表现。结论本实验方法可成功制作出现慢性自发性癫痫发作的恒河猴TLE模型，其脑电图及行为学表现与人类相似。

Objective To describe a rhesus monkey model of temporal lobe epilepsy （TLE） established via repetitive unilateral intra-amygdala kainic acid （KA） injection and provide experimental basis for epileptogenic network and related research. Methods Eight male adult rhesus monkeys wererandomly divided into KA injection group （n=6） and saline injection group （n=2）. Brain stereotaxic technique, micro catheter implantation into the right amygdaloid nucleus, subcutaneous bladder connection, and continuous video-EEG monitoring were perforrned, and KA or saline injection into their right arnygdala was achieved, lnterictal epileptic discharges （IEDs）, ictal discharges and behavioural perlbnnance between the two groups were compared right after injection and within 6 months of first discharge. Results Typical IEDs were recorded in the 6 monkeys from KA injection group after 2-4 times of KA injection, with focal spike waves discharges at the right temple area as manifestation; ictal discharges were recorded in 4 monkeys, with discharge patterns of discharges from the right temple area to the whole brain as manifestation, and during epileptic attack, these 4 monkeys suddenly stopped and dumbIbunded without obvious limb seizures. Monkeys from the saline injection group showed no obvious abnonnal behaviors. Conclusion Through a modified protocol of unilateral repetitive intra-amygda/a KA injection, a rhesus monkey model with high similarity of behavioral and brain electrical features to TLE is developed.