The Effect of Thymoquinone on the Characteristics of the Brain Extracellular Space in Transient Middle Cerebral Artery Occlusion Rats

Biol Pharm Bull. 2020;43(9):1306-1314. doi: 10.1248/bpb.b19-00991.

Abstract

The extracellular space (ECS) is the space between the neurons and the capillaries in the brain. The volume fraction (α) and the tortuosity (λ) are the main parameters used to describe its characteristics. Thymoquinone has been proved to possess anti-oxidant and anti-inflammatory activity. In this study, we used a gadolinium-diethylenetriaminepentacetate (Gd-DTPA)-enhanced magnetic resonance imaging (MRI) system to determine the effects of thymoquinone on ECS parameters in transient middle cerebral artery occlusion rats (tMCAO) to prove the neuroprotective effect of thymoquinone on brain tissue damage caused by ischemic stroke. Neurological examinations, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining and assaying of ECS parameters using MRI were performed 24 h after surgery. We found that thymoquinone could improve the behavioural performance by neurological examinations. TTC staining indicated that thymoquinone significantly decreased the percentage of hemi-cerebral infarction. Also, H&E staining showed that thymoquinone could inhibit the neuron necrosis in the hippocampal CA1 region. We found that thymoquinone treatment could inhibit the changes in ECS diffusion parameters, which might prove that thymoquinone might protect brain tissue damage caused by ischemic stroke. Thymoquinone can protect the brain against cerebral ischemia-reperfusion injury, effectively ameliorate abnormalities in characteristics of ECS and decrease cerebral infarction in tMCAO rats.

Keywords: brain extracellular space (ECS); ischemia–reperfusion injury; magnetic resonance imaging (MRI); thymoquinone; tortuosity; volume fraction.

MeSH terms

  • Animals
  • Benzoquinones / administration & dosage*
  • Brain / cytology
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / pathology
  • Disease Models, Animal
  • Extracellular Space / diagnostic imaging
  • Extracellular Space / drug effects
  • Humans
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / diagnosis
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology
  • Ischemic Stroke / diagnosis
  • Ischemic Stroke / drug therapy*
  • Ischemic Stroke / etiology
  • Ischemic Stroke / pathology
  • Magnetic Resonance Imaging
  • Male
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Benzoquinones
  • Neuroprotective Agents
  • thymoquinone