Neuroprotective effect of Da Chuanxiong Formula against cognitive and motor deficits in a rat controlled cortical impact model of traumatic brain injury

J Ethnopharmacol. 2018 May 10:217:11-22. doi: 10.1016/j.jep.2018.02.004. Epub 2018 Feb 6.

Abstract

Ethnopharmacological relevance: 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.

Aim of study: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Chuanxiong Rhizoma; Da Chuanxiong Formula; Gastrodiae Rhizoma; Neuroprotective effect; Traumatic brain injury.

MeSH terms

  • Animals
  • Apiaceae
  • Astrocytes / drug effects
  • Astrocytes / pathology
  • Behavior, Animal / drug effects*
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology
  • Blood-Brain Barrier / physiopathology
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Brain Edema / prevention & control
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / physiopathology
  • Brain Injuries, Traumatic / psychology
  • Capillary Permeability / drug effects
  • Cell Proliferation / drug effects
  • Cerebral Cortex / drug effects*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Cognition / drug effects*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / pharmacology*
  • Gait / drug effects
  • Gastrodia
  • Male
  • Maze Learning / drug effects
  • Microglia / drug effects
  • Microglia / pathology
  • Motor Activity / drug effects*
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / pathology
  • Neurogenesis / drug effects
  • Neuroprotective Agents / pharmacology*
  • Rats, Sprague-Dawley
  • Rhizome
  • Rotarod Performance Test
  • Time Factors

Substances

  • Drugs, Chinese Herbal
  • Neuroprotective Agents