Resveratrol has been shown to exert anti-inflammatory and anti-aging effects in vitro and in animal models. Resveratrol inhibits the activity of several inflammatory enzymes in vitro, including cyclooxygenase and lipoxygenase, resulting in a suppressive effect upon inflammatory and oxidative stress (Ghanim et al., 2010). Resveratrol also may inhibit proinflammatory transcription factors, such as NFκB or AP-1. Other mechanisms by which resveratrol may improve brain injury effects are restoration of cerebral blood flow, repair of neural loss, and scavenging of free radicals.
Recent evidence suggests that SIRT12 inhibitors may be neuroprotective; however, resveratrol does not appear to act directly as a SIRT1 inhibitor (Tang, 2010), because it does not activate SIRT1 during the acute phase of neuronal cell demise. Resveratrol may indirectly increase SIRT1 activity in recovering or spared cells via elevation by 5′ AMP-activated protein kinase (AMPK) of NAD+ levels, which then translates into an overall beneficial outcome (activation of AMPK, another enzyme with a key role in cellular energy homeostasis, may be neuroprotective). Table 14-2 lists studies (from 1990 and after) evaluating the effectiveness of resveratrol in providing resilience or treating TBI or related diseases or conditions (i.e., subarachnoid hemorrhage, intracranial aneurysm, stroke, anoxic or hypoxic ischemia, epilepsy) in the acute phases.
An expanding body of preclinical evidence suggests resveratrol may be beneficial in treating a variety of human diseases. For this reason, resveratrol is being sold as a dietary supplement, despite the absence of definitive information about resveratrol’s effects in humans, and while research into the potential health benefits of resveratrol is continuing. As with other food components, it appears that the health benefits of resveratrol are dose-dependent. Low doses of resveratrol have been found to lead to beneficial health outcomes, while high doses of resveratrol can be detrimental to health (Mukherjee et al., 2010). High doses of resveratrol may, however, be required for treatment of pathological conditions, such as destruction of cancer cells (Mukherjee et al., 2010).
A 2011 review describes the available clinical data on safety and potential mechanisms of action following multiple dosing with resveratrol (Patel et al., 2011). The review acknowledged that a complete picture of the safety of resveratrol could not be asserted, because out of 16 clinical trials, only 5 included information on adverse effects, and only 1 of these studies included a placebo control group. Still, the authors found resveratrol to be safe and reasonably well tolerated at doses of up to 5 g/day. The review found some mild to moderate side effects, such as gastrointestinal disturbances, if used at doses higher than 1 g/day.
There have been no human trials or observational studies conducted to study resveratrol’s potential to impart resilience against TBI. Likewise, there are no human studies to assess the effect of resveratrol on subarachnoid or intracranial hemorrhage, intracranial aneurysm, ischemia, stroke, or epilepsy.