Neuroprotective properties of the natural vitamin E alpha-tocotrienol

Stroke. 2005 Oct;36(10):2258-64. doi: 10.1161/01.STR.0000181082.70763.22. Epub 2005 Sep 15.


Background and purpose: The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of alpha-tocotrienol (TCT), but not alpha-tocopherol (TCP), blocked glutamate-induced death by suppressing early activation of c-Src kinase and 12-lipoxygenase.

Methods: The single neuron microinjection technique was used to compare the neuroprotective effects of TCT with that of the more widely known TCP. Stroke-dependent brain tissue damage was studied in 12-Lox-deficient mice and spontaneously hypertensive rats orally supplemented with TCT.

Results: Subattomole quantity of TCT, but not TCP, protected neurons from glutamate challenge. Pharmacological as well as genetic approaches revealed that 12-Lox is rapidly tyrosine phosphorylated in the glutamate-challenged neuron and that this phosphorylation is catalyzed by c-Src. 12-Lox-deficient mice were more resistant to stroke-induced brain injury than their wild-type controls. Oral supplementation of TCT to spontaneously hypertensive rats led to increased TCT levels in the brain. TCT-supplemented rats showed more protection against stroke-induced injury compared with matched controls. Such protection was associated with lower c-Src activation and 12-Lox phosphorylation at the stroke site.

Conclusions: The natural vitamin E, TCT, acts on key molecular checkpoints to protect against glutamate- and stroke-induced neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antioxidants / pharmacology*
  • Arachidonate 12-Lipoxygenase / metabolism
  • Brain / pathology
  • CSK Tyrosine-Protein Kinase
  • Cell Death
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • Cerebral Cortex / embryology
  • Fluoresceins
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Hippocampus / cytology
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / metabolism
  • Neuroprotective Agents / pharmacology*
  • Organic Chemicals / pharmacology
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins pp60(c-src) / metabolism
  • Random Allocation
  • Rats
  • Rats, Inbred SHR
  • Stroke / metabolism
  • Stroke / pathology
  • Time Factors
  • Tocotrienols
  • Transfection
  • Tyrosine / chemistry
  • Vitamin E / analogs & derivatives*
  • Vitamin E / chemistry
  • Vitamin E / metabolism
  • Vitamin E / pharmacology
  • src-Family Kinases / metabolism


  • Antioxidants
  • Fluoresceins
  • Neuroprotective Agents
  • Organic Chemicals
  • Tocotrienols
  • fluoro jade
  • Vitamin E
  • Glutamic Acid
  • Tyrosine
  • tocotrienol, alpha
  • Arachidonate 12-Lipoxygenase
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases