DL-3-n-butylphthalide-induced neuroprotection in rat models of asphyxia-induced cardiac arrest followed by cardiopulmonary resuscitation

J Cell Physiol. 2021 Nov;236(11):7464-7472. doi: 10.1002/jcp.30442. Epub 2021 Jun 1.

Abstract

Most patients that resuscitate successfully from cardiac arrest (CA) suffer from poor neurological prognosis. DL-3-n-butylphthalide (NBP) is known to have neuroprotective effects via multiple mechanisms. This study aimed to investigate whether NBP can decrease neurological impairment after CA. We studied the protective role of NBP in the hippocampus of a rat model of cardiac arrest induced by asphyxia. Thirty-nine rats were divided randomly into sham, control, and NBP groups. Rats in control and NBP groups underwent cardiopulmonary resuscitation (CPR) 6 min after asphyxia. NBP or vehicle (saline) was administered intravenously 10 min after the return of spontaneous circulation (ROSC). Ultrastructure of hippocampal neurons was observed under transmission electron microscope. NBP treatment improved neurological function up to 72 h after CA. The ultrastructural lesion in mitochondria recovered in the NBP-treated CA model. In conclusion, our study demonstrated multiple therapeutic benefits of NBP after CA.

Keywords: L-3-n-butylphthalide; asphyxia-induced cardiac arrest model; hippocampal neuron; neuroprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Asphyxia / complications
  • Benzofurans / pharmacology*
  • Brain Diseases / etiology
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Brain Diseases / prevention & control*
  • Cardiopulmonary Resuscitation / adverse effects*
  • Disease Models, Animal
  • Heart Arrest / etiology
  • Heart Arrest / physiopathology
  • Heart Arrest / therapy*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Neuroprotection / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Phosphorylation
  • Rats
  • Rats, Sprague-Dawley
  • Return of Spontaneous Circulation
  • Signal Transduction
  • Time Factors
  • p38 Mitogen-Activated Protein Kinases / metabolism
  • tau Proteins / metabolism

Substances

  • Benzofurans
  • Mapt protein, rat
  • NF-kappa B
  • Neuroprotective Agents
  • tau Proteins
  • 3-n-butylphthalide
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases