Resveratrol neuroprotection in stroke and traumatic CNS injury

Abstract

Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection.

Keywords: CNS injury; Inflammation; Ischemia; Neuroprotection; Oxidative stress; Polyphenols.

Fig. 1

Resveratrol induces a neuroprotective state via several disparate pathways. The exact mechanism of resveratrol-mediated neuroprotection is not yet understood, but the downstream anti-oxidative, anti-inflammatory and anti-apoptotic effectors have been well documented. This diagram illustrates the factors responsible for inducing a pro-survival state after resveratrol treatment in the CNS. Note that some effectors, particularly SIRT1 and AMPK can be activated or inhibited by more than one pathway. Arrows with a point indicate activation, while arrows with a flat tip indicate inhibition. White arrows indicate activation/inhibition via an indirect or poorly understood mechanism. Green = role in inflammation. Pink = role in oxidative stress. Blue = role in apoptosis. White = transcription factor or pathway intermediary.

Figure 2

Many pathophysiologic mechanisms that start within minutes and continue for days synergistically promote neuronal death following ischemic and traumatic injuries to CNS. Resveratrol treatment was shown to prevent secondary brain damage by curtailing several of these mechanisms, including excitotoxicity, edema, apoptosis, oxidative and nitrosative stress, inflammation and BBB disruption (shown by a purple box). Effects of resveratrol on mechanisms such as non-coding RNAs and epigenetics that are also important modulators of secondary brain damage were not yet evaluated.