Neurology Department, Hunan Academy of Chinese Medicine Affiliated Hospital.
Foreign Languages Department, School of Humanities and Management, Hunan University of Chinese Medicine.
Neuroreport. 2021 Oct 6;32(14):1183-1191. doi: 10.1097/WNR.0000000000001709.
K+-Cl- cotransporter-2 (KCC2), which primarily extrudes chloride in mature neurons, triggers hemiplegia limb spasticity after ischemic stroke by affecting neuronal excitability. Our previous study revealed that the Chinese herb Baishaoluoshi Decoction decreases hemiplegia limb spasticity in poststroke spasticity (PSS) patients. This study aimed at elucidating on the effects of Baishaoluoshi Decoction on the BDNF/TrKB-KCC2 pathway in PSS rat models.
Middle cerebral artery occlusion (MCAO) was adopted for the establishment of PSS rat models. Muscle tension was evaluated by Modified Ashworth Scale. Nissl staining and transmission electron microscopy were used to measure the protective effects of Baishaoluoshi Decoction on ischemic injury-induced neuronal damage due to MCAO. Expression levels of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were detected by immunohistochemical staining.
It was found that Baishaoluoshi Decoction suppressed hemiplegia limb spasticity and alleviated the damage in neurons and synapses in PSS rat models. Importantly, the expression of BDNF, TrKB, and KCC2 in brain tissues around the infarct and brainstem were significantly upregulated after treatment with low-dose and high-dose Baishaoluoshi Decoction.
Suppression of spasticity by Baishaoluoshi Decoction in PSS rat models may be correlated with upregulated BDNF/TrKB-KCC2 pathway, which may be a complementary therapeutic strategy for PSS.
K+-Cl-共转运蛋白-2(KCC2)主要在成熟神经元中排出氯离子,通过影响神经元兴奋性引发缺血性中风后的偏瘫肢体痉挛。我们之前的研究表明,中药白沙络石汤可降低中风后痉挛(PSS)患者的偏瘫肢体痉挛。本研究旨在阐明白沙络石汤对 PSS 大鼠模型中脑源性神经营养因子/TrKB-KCC2 通路的影响。
采用大脑中动脉闭塞(MCAO)建立 PSS 大鼠模型。改良 Ashworth 量表评估肌肉张力。尼氏染色和透射电镜测量白沙络石汤对 MCAO 引起的缺血性损伤诱导的神经元损伤的保护作用。免疫组织化学染色检测脑梗死周围和脑干脑组织中脑源性神经营养因子(BDNF)、TrKB 和 KCC2 的表达水平。
发现白沙络石汤抑制偏瘫肢体痉挛,减轻 PSS 大鼠模型中神经元和突触的损伤。重要的是,低剂量和高剂量白沙络石汤治疗后,脑梗死周围和脑干脑组织中 BDNF、TrKB 和 KCC2 的表达明显上调。
白沙络石汤抑制 PSS 大鼠模型痉挛可能与上调的 BDNF/TrKB-KCC2 通路有关,这可能是 PSS 的一种补充治疗策略。