Proteomic changes in the hippocampus and motor cortex in a rat model of cerebral palsy: Effects of topical treatment

Biomed Pharmacother. 2021 Jan:133:110844. doi: 10.1016/j.biopha.2020.110844. Epub 2020 Nov 11.

Abstract

Cerebral palsy (CP) is a non-progressive motor-impairment disorder related to brain injury early in development. To gain new insights into the mechanisms of CP and the therapeutic efficacy of Baimai ointment, we used a high-throughput quantitative proteomic approach to evaluate proteomic changes in the hippocampus and motor cortex in a rat model of CP induced by lipopolysaccharide (LPS) combined with hypoxia/ischemia (H/I). More than 2000 proteins were identified in each brain region with high confidence. Quantitative analysis demonstrated profound disturbances in the proteomes of the hippocampus and motor cortex after LPS + H/I, in addition to the disruption of the motor system. In contrast, the topical application of Baimai ointment not only alleviated the motor deficit in the CP model rats, but also restored the proteomes in the brain cortex. Furthermore, astrocytes in the hippocampus were strongly activated in the Baimai-treated CP rat brains, associated with an increase in neurotrophic factors. Proteomic analysis demonstrated that the CP model induced neuroinflammatory responses in the brain which were reversed by the topical application of Baimai ointment. This study highlights the unexpected roles of hippocampus and motor cortex neurons in CP progress and treatment, thus providing potentially novel therapeutic targets for CP.

Keywords: Cerebral palsy; Hippocampus; Motor cortex; Proteomics.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Behavior, Animal / drug effects*
  • Cerebral Palsy / drug therapy*
  • Cerebral Palsy / metabolism
  • Cerebral Palsy / physiopathology
  • Chromatography, High Pressure Liquid
  • Chromatography, Reverse-Phase
  • Disease Models, Animal
  • Drugs, Chinese Herbal / administration & dosage*
  • Drugs, Chinese Herbal / pharmacology
  • Female
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / physiopathology
  • Male
  • Motor Activity / drug effects*
  • Motor Cortex / drug effects*
  • Motor Cortex / metabolism
  • Motor Cortex / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism
  • Ointments
  • Pregnancy
  • Proteome*
  • Proteomics*
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry

Substances

  • Drugs, Chinese Herbal
  • Ointments
  • Proteome
  • baimai ointment