Xie Yao, Qin Shenglan, Zhang Rui, Wu Hong, Sun Guoyu, Liu Lili, Hou Xinlin
Pediatric Department, Peking University First Hospital, Beijing, China.
Pediatric Department, People's Hospital of Tibet Autonomous Region, Tibet, China.
Front Pediatr. 2020 Sep 10;8:561. doi: 10.3389/fped.2020.00561. eCollection 2020.
In this study, we examined the effects of high-altitude environment on the brain function of a young-rat seizure model. Two-hundred healthy, 3-week old, male rats were selected and equally divided into the plateau and plain groups. The plateau group was preconditioned in a simulated 5,000-m altitude (barometric pressure [PB], 405 mmHg; partial pressure of oxygen [PO], 84 mmHg) for 6 h/day for 7 days, while the plain group was kept in the ordinary atmospheric environment (PB, 760 mmHg; PO, 157 mmHg) for 7 days. After preconditioning, rats were administered pentylenetetrazol (PTZ) to generate level-4 or stronger seizures. Electroencephalogram (EEG) signals were recorded (16 rats/group); the histology and apoptosis of hippocampal tissue were evaluated (6 rats/group); and spatial learning and memory were examined in the Morris water maze (12 rats/group; 6-weeks old). To induce a level 4 or stronger seizure successfully, a significantly higher PTZ dose was used in the plateau (81.32 ± 21.57 mg/kg) than in the plain group (63.41 ± 19.77 mg/kg, < 0.01); however, the plateau group survival rate was significantly lower than that of the plain group (26.2 vs. 42.9%, < 0.05). EEG parameters did not differ between the two groups. Histological analysis revealed that in the plateau group, more neurons were observed ( < 0.001), especially in DG and CA1 areas, and less apoptotic cells were found in DG areas ( = 0.035), comparing with the plain group. No differences were found between the two groups in any of the parameters examined in the Morris water maze. Our results show that the disease outcome caused by low pressure and low oxygen environment in the plateau group was different to that in the plain group. The high drug dosage to induce seizures in the plateau group, accompanied by increased mortality rates after seizures, indicates that the seizure threshold may be higher in the plateau than in the plain group. Moreover, based on the histological findings, the plateau environment seems to exert a protective effect on brain development after seizures only for survived individuals with mild conditions.
在本研究中，我们检测了高海拔环境对幼鼠癫痫模型脑功能的影响。选取200只健康的3周龄雄性大鼠，将其平均分为高原组和平原组。高原组在模拟海拔5000米（气压[PB]，405 mmHg；氧分压[PO]，84 mmHg）的环境中预处理，每天6小时，共7天；而平原组在普通大气环境（PB，760 mmHg；PO，157 mmHg）中饲养7天。预处理后，给大鼠注射戊四氮（PTZ）以诱发4级或更强的癫痫发作。记录脑电图（EEG）信号（每组16只大鼠）；评估海马组织的组织学和细胞凋亡情况（每组6只大鼠）；并在莫里斯水迷宫中检测空间学习和记忆能力（每组12只大鼠；6周龄）。为成功诱发4级或更强的癫痫发作，高原组使用的PTZ剂量（81.32±21.57 mg/kg）显著高于平原组（63.41±19.77 mg/kg，P<0.01）；然而，高原组的存活率显著低于平原组（26.2%对42.9%，P<0.05）。两组的EEG参数没有差异。组织学分析显示，与平原组相比，高原组观察到更多的神经元（P<0.001），尤其是在齿状回（DG）和海马体1区（CA1），并且在DG区发现的凋亡细胞较少（P=0.035）。在莫里斯水迷宫中检测的任何参数上，两组之间均未发现差异。我们的结果表明，高原组由低压低氧环境导致的疾病结果与平原组不同。高原组诱发癫痫发作所需的药物剂量较高，且癫痫发作后的死亡率增加，这表明高原组的癫痫发作阈值可能高于平原组。此外，基于组织学结果，高原环境似乎仅对癫痫发作后病情较轻的存活个体的脑发育具有保护作用。
