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(Stroke. 2005;36:e144.)
© 2005 American Heart Association, Inc.

Original Contributions

Neuroprotective Properties of the Natural Vitamin E -Tocotrienol

Savita Khanna, PhD; Sashwati Roy, PhD; Andrew Slivka, MD; Tara K.S. Craft, MA; Soma Chaki, PhD; Cameron Rink, BS; Margaret A. Notestine, BA; A. Courtney DeVries, PhD; Narasimham L. Parinandi, PhD Chandan K. Sen, PhD

From the Departments of Surgery (S.K., S.R., S.C., C.R., C.K.S.), Neurology (A.S., M.A.N.), and Internal Medicine (N.L.P.), The Ohio State University Medical Center, Columbus, Ohio; and the Department of Psychology (T.K.S.C., A.C.D.), The Ohio State University, Columbus, Ohio.

Correspondence to Chandan K. Sen, PhD, 512 DHLRI, 473 W 12th Ave, OSU, Columbus, OH 43210. E-mail sen-1{at}medctr.osu.edu

Background and Purpose— The current work is based on our previous finding that in neuronal cells, nmol/L concentrations of -tocotrienol (TCT), but not -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.

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

Key Words: nutrition • pathophysiology • vitamin

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