Following this crucial finding, a series of studies funded by the NIH continued to establish further unique mechanisms instrumental to the neuroprotective and stroke prevention properties of tocotrienols. Tocomin and Tocomin SupraBio were used in these studies.

The neuroprotection against stroke-induced cell death by tocotrienols can be classified into actions at the cellular and cerebrovascular levels:

1) Neuroprotection at cellular (neuronal) level: Tocotrienol-mediated neuroprotection includes at least three key cytosolic targets: c-Src kinase, 12-lypoxygenase and phospholipase A2 (Sen et al, 2000; Khanna et al, 2005, 2010). Both c-Src kinase and 12-lypoxygenase are capable of triggering a cascade of events that lead to eventual neuronal cell degeneration and death. Tocotrienol was found to reduce c-Src kinase activation and 12-lypoxygenase phosphorylation. 

2) Neuroprotection at cerebrovascular level: In ischemic stroke, the primary event stems from a reduction in cerebral blood to a level that cannot sustain neuronal survival. Work with catheter angiography in canine models showed that tocotrienol (Tocomin SupraBio) supplementation enhanced leptomeningeal collateralization, specifically from the anterior cerebral and posterior cerebral arteries to the middle cerebral artery territory. Increasing this secondary source of blood supply reduces the volume of induced middle cerebral artery territory infarcts, as seen in animal stroke models on MRI.

This is further explained and supported by a subsequent study, which shows increased expression of arteriogenic genes with tocotrienol supplementation, including gene expression of chloride intracellular channel 1 and TIMP1. Perhaps more importantly, the study also shows that the increased gene expression occurred not only on the induced stroke site but also normal brain tissue (Rink and others, 2011).