4.7 Article

7,8-Dihydroxyflavone accelerates recovery of Brown-Sequard syndrome in adult female rats with spinal cord lateral hemisection

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 153, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113397

Keywords

7 8-Dihydroxyflavone. Brown-Sequard Syndrome. Spinal cord hemisection. Motor evoked potentials

Funding

  1. Innovation Project in Military Medicine Research Project, PLA [19QNP087]
  2. Foundation of the Director of the 960th Hospital Joint Logistics Support Force of PLA [2018ZX03]
  3. Logistics Research Program, PLA [2019-JCJQ-ZNM-02]
  4. Ministry of Science and Technology (Taipei, Taiwan) [MOST 108-2314-B-715-001]
  5. Mackay Memorial Hospital [MMH-MM-10807]
  6. Mackay Medical College [1081A01]

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This study investigated the therapeutic effects of 7,8-Dihydroxyflavone (DHF) in a rat model of Brown-Sequard Syndrome. The results showed that DHF accelerated the electrical, histological, and functional recovery in animals with Brown-Sequard Syndrome.
Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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