Neuroprotective Effects of Tocovid Pretreatment in a Mouse Stroke Model

J Stroke Cerebrovasc Dis. 2018 Aug;27(8):2166-2174. doi: 10.1016/j.jstrokecerebrovasdis.2018.03.014. Epub 2018 May 24.

Abstract

Background: Tocovid is a new combination of tocotrienols and tocopherol, both of which are neuroprotective agents for preventing cerebral infarction in mice. However, the effects of tocovid on anti-inflammation in ischemic model remain elusive. In the present study, we assessed the effects of Tocovid pretreatment on anti-inflammatory effects after transient middle cerebral occlusion (tMCAO) in mice.

Materials and methods: We evaluated the therapeutic and anti-inflammatory effects of tocovid pretreatment (200 mg/kg per day, for 1 month) on mice brain under 60 minutes of tMCAO. The expressive changes of inflammatory markers were observed after tMCAO in mice.

Results: Tocovid pretreatment greatly improved the mice neurobehaviors, reduced infarct volumes and decreased expressions of inflammatory markers such as tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1) and ionized calcium binding adapter molecule-1 (Iba-1), and improved the damage of neurovascular units including matrix metallopeptidase 9, IgG and collagen IV after tMCAO.

Conclusions: Our present findings demonstrated that oral tocovid pretreatment showed obviously neuroprotective and at least in part by anti-inflammatory effects in ischemic mice brain.

Keywords: Neuroinflammation; neurovascular unit dissociation; tocovid; transient middle cerebral occlusion.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Brain / drug effects
  • Brain / immunology
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism
  • Chemokine CCL2 / metabolism
  • Collagen / metabolism
  • Disease Models, Animal
  • Immunoglobulin G / metabolism
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / immunology
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, Inbred ICR
  • Microfilament Proteins / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neurovascular Coupling / drug effects
  • Neurovascular Coupling / physiology
  • Random Allocation
  • Time Factors
  • Tocotrienols / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Aif1 protein, mouse
  • Anti-Inflammatory Agents
  • Calcium-Binding Proteins
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Immunoglobulin G
  • Microfilament Proteins
  • Neuroprotective Agents
  • Tocotrienols
  • Tocovid
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse