Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
UCLA Children's Discovery and Innovation Institute, Los Angeles, California, USA.
Epilepsia. 2021 Jun;62(6):1472-1481. doi: 10.1111/epi.16909. Epub 2021 Apr 23.
Traumatic brain injury (TBI) may lead to the disruption of the intestinal barrier (IB), and to the escape of products of commensal gut bacteria, including lipopolysaccharide (LPS), into the bloodstream. We examined whether lateral fluid percussion injury (LFPI) and post-traumatic epilepsy (PTE) are associated with the increased intestinal permeability and endotoxemia, and whether these events in turn are associated with PTE.
LFPI was delivered to adult male Sprague-Dawley rats. Before, 1 week, and 7 months after LFPI, the IB permeability was examined by measuring plasma concentration of fluorescein isothiocyanate-labeled dextran (FD4) upon its enteral administration. Plasma LPS concentration was measured in the same animals, using enzyme-linked immunosorbent assay. PTE was examined 7 months after LFPI, with use of video-EEG (electroencephalography) monitoring.
One week after LFPI, the IB disruption was detected in 14 of 17 and endotoxemia - in 10 of 17 rats, with a strong positive correlation between FD4 and LPS levels, and between plasma levels of each of the analytes and the severity of neuromotor deficit. Seven months after LFPI, IB disruption was detected in 13 of 15 and endotoxemia in 8 of 15 rats, with a strong positive correlation between plasma levels of the two analytes. Five of 15 LFPI rats developed PTE. Plasma levels of both FD4 and LPS were significantly higher in animals with PTE than among the animals without PTE. The analysis of seven rats, which were examined repeatedly at 1 week and at 7 months, confirmed that late IB disruption and endotoxemia were not due to lingering of impairments occurring shortly after LFPI.
LFPI leads to early and remote disruption of IB and a secondary endotoxemia. Early and late perturbations may occur in different subjects. Early changes reflect the severity of acute post-traumatic motor dysfunction, whereas late changes are associated with PTE.
创伤性脑损伤（TBI）可能导致肠道屏障（IB）破坏，并使共生肠道细菌的产物，包括脂多糖（LPS），进入血液。我们研究了外侧液冲击伤（LFPI）和创伤后癫痫（PTE）是否与肠通透性增加和内毒素血症有关，以及这些事件是否反过来与 PTE 有关。
对成年雄性 Sprague-Dawley 大鼠进行 LFPI。在 LFPI 之前、1 周和 7 个月后，通过测量经口给予荧光素异硫氰酸酯标记的葡聚糖（FD4）后血浆浓度来检查 IB 通透性。在相同动物中使用酶联免疫吸附测定法测量血浆 LPS 浓度。在 LFPI 后 7 个月，使用视频-EEG（脑电图）监测检查 PTE。
LFPI 后 1 周，17 只大鼠中有 14 只出现 IB 破坏，17 只大鼠中有 10 只出现内毒素血症，FD4 和 LPS 水平之间以及两种分析物的血浆水平与神经运动缺陷的严重程度之间存在强烈的正相关。LFPI 后 7 个月，15 只大鼠中有 13 只出现 IB 破坏，15 只大鼠中有 8 只出现内毒素血症，两种分析物的血浆水平之间存在强烈的正相关。15 只 LFPI 大鼠中有 5 只发生 PTE。患有 PTE 的动物的 FD4 和 LPS 血浆水平明显高于未患有 PTE 的动物。对 7 只在 1 周和 7 个月时重复检查的大鼠进行的分析证实，晚期 IB 破坏和内毒素血症不是由于 LFPI 后不久发生的持续性损伤所致。
LFPI 导致早期和晚期 IB 破坏和继发性内毒素血症。早期和晚期的变化可能发生在不同的个体中。早期变化反映了急性创伤后运动功能障碍的严重程度，而晚期变化与 PTE 有关。
