Multimodal Rehabilitation Program Promotes Motor Function Recovery of Rats After Ischemic Stroke by Upregulating Expressions of GAP-43, SYN, HSP70, and C-MYC

J Stroke Cerebrovasc Dis. 2018 Oct;27(10):2829-2839. doi: 10.1016/j.jstrokecerebrovasdis.2018.06.018. Epub 2018 Aug 6.

Abstract

Background: Despite the intense efforts devoted to preventing and treating cerebral ischemia, some individuals will continue to have completed infarctions. Failure of prevention or intervention does not, however, preclude therapeutic approaches to enhance recovery. Our study aims to explore the effect of multimodal rehabilitation program on the motor function recovery of rats with ischemic stroke.

Methods: Rat models of ischemic stroke were established using clean-grade adult male Sprague-Dawley rats. Motor function of rats was scored by the Bederson neurological function, balance beam test, and screen test. Nissl staining was conducted for morphological and structural changes of nerve cells in the arteriae cerebri anterior zone. Immunohistochemistry was applied to detect the expressions of growth-associated protein (GAP-43), synaptophysin (SYN) and Caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining was carried out in the corpus striatum 21 days after operation; reverse transcription quantitative polymerase chain reaction and Western blot analysis were conducted for testing messager RNA (mRNA) and protein expressions of heat shock protein 70 (Hsp70) and MYC proto-oncogene (c-Myc).

Results: Rats receiving multimodal rehabilitation program had lower Bederson neurological function, balance beam, and screen test scores on the 7th, 14th and 21st days after operation; more number of neurons surviving in the arteriae cerebri anterior zone at each time point after operation, higher GAP-43 expression on the 7th and 14th days after operation, and higher SYN expression on the 14th and 21st days after operation, on the 7th, 14th and 21st days after operation, higher mRNA and protein expressions of HSP70 and C-MYC, lower Caspase-3 positive expression and TUNEL positive stained cells.

Conclusions: Multimodal rehabilitation program could promote motor function recovery of rats after ischemic stroke by upregulating GAP-43 and SYN expressions at arteriae cerebri anterior zone and upregulating HSP70 and C-MYC expressions in the brain tissues.

Keywords: Multimodal rehabilitation program—ischemic stroke—motor function—neural function—heat shock protein 70—cellular-myelocytomatosis—growth-associated protein-43—synaptophysin.

MeSH terms

  • Animals
  • Apoptosis
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology
  • Brain Ischemia / rehabilitation*
  • Combined Modality Therapy
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • Corpus Striatum / physiopathology
  • Disease Models, Animal
  • GAP-43 Protein / genetics
  • GAP-43 Protein / metabolism*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Male
  • Motor Activity*
  • Neurons / metabolism
  • Neurons / pathology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Stroke / metabolism
  • Stroke / physiopathology
  • Stroke / therapy*
  • Stroke Rehabilitation / methods*
  • Synaptophysin / genetics
  • Synaptophysin / metabolism*
  • Time Factors
  • Up-Regulation

Substances

  • GAP-43 Protein
  • HSP70 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-myc
  • Synaptophysin
  • Syp protein, rat