Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China; State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China.
Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China.
J Ethnopharmacol. 2018 May 10;217:11-22. doi: 10.1016/j.jep.2018.02.004. Epub 2018 Feb 6.
Da Chuanxiong Formula (DCXF) is one of the famous herb pairs that contains dried rhizomes of Ligusticum chuanxiong Hort. and Gastrodia elata Bl. in the mass ratio of 4:1. This classic representative traditional Chinese medicine has been widely used to treat brain diseases like headache and migraine caused by blood stasis and wind pathogen. However, the therapeutic effect of DCXF on traumatic brain injury (TBI) has not been reported yet.
The present study was performed to investigate the neuroprotective effects of DCXF and its underlying mechanisms in the controlled cortical impact (CCI)-induced TBI rat model.
Male Sprague-Dawley rats were divided into four groups: Sham, TBI control, 1X DCXF (520.6 mg/kg) and 5X DCXF (2603.0 mg/kg). Two treatment groups (1X and 5X DCXF) were intragastrically administered daily for 7 days before CCI-induced TBI and then DCXF treatments were continued post-TBI until the animal behavioral tests, including Morris water maze test, acceleration rotarod motor test and CatWalk quantitative gait analysis test, were done. The brain water content and blood brain barrier (BBB) integrity were measured by wet-dry weight method and Evans blue method, respectively. The number of neuron cells, neural stem cells (NSCs), GFAP positive cells (astrocyte) as well as Iba-1 positive cells (microglia) were determined by histology and immunohistochemistry.
Treatment with DCXF significantly improved the learning ability and memory retention in Morris water maze test, and remarkably enhanced motor performances in acceleration rotarod motor test and catwalk quantitative gait analysis test after TBI. Moreover, DCXF treatment was able to reduce BBB permeability, brain edema, microglia and astrocyte activation, improve the proliferation of NSCs and decrease neurons loss in the brain with TBI.
The present study demonstrated that DCXF treatment could decrease BBB leakage and brain edema, reduce neuron loss, microglia and astrocyte activation, and increase NSCs proliferation, which may contribute to the cognitive and motor protection of DCXF in the TBI rats. It is the first time to provide potentially underlying mechanisms of the neuroprotective effect of DCXF on TBI-induced brain damage and functional outcomes.
大川芎方（DCXF）是一种著名的药对，由川芎和天麻的干根茎按 4:1 的质量比组成。这种经典的中药代表方剂已被广泛用于治疗血瘀和风邪引起的头痛和偏头痛等脑部疾病。然而，DCXF 对创伤性脑损伤（TBI）的治疗效果尚未报道。
本研究旨在探讨 DCXF 对皮质撞击（CCI）诱导的 TBI 大鼠模型的神经保护作用及其潜在机制。
雄性 Sprague-Dawley 大鼠分为四组：假手术组、TBI 对照组、1X DCXF（520.6mg/kg）组和 5X DCXF（2603.0mg/kg）组。两个治疗组（1X 和 5X DCXF）在 CCI 诱导 TBI 前每天灌胃给药 7 天，然后继续 TBI 后给药，直到进行动物行为测试，包括 Morris 水迷宫测试、加速转棒运动测试和 CatWalk 定量步态分析测试。采用干湿重法和 Evans 蓝法分别测量脑含水量和血脑屏障（BBB）完整性。通过组织学和免疫组织化学测定神经元细胞、神经干细胞（NSCs）、GFAP 阳性细胞（星形胶质细胞）和 Iba-1 阳性细胞（小胶质细胞）的数量。
DCXF 治疗可显著改善 TBI 后 Morris 水迷宫测试中的学习能力和记忆保留，显著增强加速转棒运动测试和 CatWalk 定量步态分析测试中的运动表现。此外，DCXF 治疗可降低 BBB 通透性、脑水肿、小胶质细胞和星形胶质细胞活化，促进 TBI 后 NSCs 的增殖，减少神经元丢失。
本研究表明，DCXF 治疗可降低 BBB 渗漏和脑水肿，减少神经元丢失、小胶质细胞和星形胶质细胞活化，增加 NSCs 增殖，从而有助于 DCXF 对 TBI 大鼠认知和运动功能的保护。这是首次提供 DCXF 对 TBI 诱导的脑损伤和功能结果的神经保护作用的潜在机制。
