Department of Spinal Cord Injury and Repair, Trauma and Orthopedics Institute of Chinese PLA, the 960th Hospital of Joint Logistics Support Force of PLA, Shandong Province, PR China; Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, PR China.
Department of Spinal Cord Injury and Repair, Trauma and Orthopedics Institute of Chinese PLA, the 960th Hospital of Joint Logistics Support Force of PLA, Shandong Province, PR China; Institute of Military Cognitive and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, PR China; Department of Orthopaedics, Shandong Provincial Third Hospital, Shandong University, Shandong province, PR China.
Biomed Pharmacother. 2022 Sep;153:113397. doi: 10.1016/j.biopha.2022.113397. Epub 2022 Jul 13.
7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level.
Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated.
Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals.
Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.
7,8-二羟基黄酮（DHF）模拟脑源性神经营养因子（BDNF）的生理作用。由于局部 BDNF 递送到损伤的脊髓增强了膈呼吸功能，我们旨在确定 DHF 是否可能在 T9 水平脊髓侧半切（HX）大鼠模型中具有类似的有益作用Brown-Sequard 综合征后。
三组成年雌性大鼠包括：假手术+载体组、T9HX+载体组和 T9HX+DHF 组。在手术当天，HX+DHF 组给予 DHF（5mg/kg），而 HX+载体组给予载体。评估神经行为功能、支配胫骨前肌的运动神经元形态和下行运动通路的传递。
成年雌性大鼠接受 T9 HX 后出现同侧瘫痪和本体感觉丧失，对侧疼痛和温度丧失。我们发现，在这种 Brown-Sequard 综合征模型中，T9HX 后出现脊髓树突复杂性降低、脊髓运动神经元数量减少、脊髓损伤体积增大、运动诱发电位降低以及脊髓星形胶质细胞和小胶质细胞增生。所有上述异常在手术后第 28 天均有恢复。DHF 治疗显著加速了这些 T9HX 动物的电生理、组织学和功能恢复。
我们的数据为 DHF 作为一种神经治疗剂提供了生物学基础，以改善 Brown-Sequard 综合征后的恢复。这种作用可能是通过 T9HX 中剩余腰髓运动神经元池的突触可塑性和胶质细胞介导的炎症介导的。
