Reference

Type of Injury/Insult

Type of Study and Subjects

Treatment

Findings/Results

Singleton et al., 2010

Control cortical impact

Randomized, placebo-controlled study

Postinjury, 10 or 100 mg/kg of resveratrol or vehicle administered intraperitoneally at 5 minutes, 1 day, and 2 days after injury

Injured rats treated with 100 mg/kg of resveratrol and sham-injured rats treated with vehicle showed significantly better motor performance on beam-balance (p < 0.01), beam walk score (p < 0.01), and beam walk (p < 0.01 tests compared to injured, vehicle-treated rats). Rats treated with 10 mg/kg of resveratrol were not significantly different from vehicle-treated rats.

adult male Sprague-Dawley rats

Cognitive performance on Morris water maze was significantly better in sham rats (p < 0.001) and in rats treated with 100 mg/kg of resveratrol (p < 0.05) than vehicle-treated rats.

Rats treated with 100 mg/kg of resveratrol had a mean contusion volume that was 10.6 mm3 smaller than injured, vehicle-treated rats (p < 0.028). Rats treated with 100 mg/kg resveratrol had more cells in the CA1 region (difference: 334.9, p < 0.001) and the CA3 region (difference: 102.5, p=0.001) of the hippocampus than injured, vehicle-treated rats. Thus, resveratrol (100 mg/kg) was significantly associated with hippocampal preservation (p=0.033).

Animal Studies

Numerous studies using rat models of ischemia reperfusion have demonstrated the ability of resveratrol, administered either intravenously or orally, to improve ischemia outcomes. The outcomes evaluated include cerebral blood flow, infarct volume, indicators of oxidative stress and inflammation, apoptotic cell death, and mitochondrial function. Studies have looked at the effects of intake of resveratrol as early as 21 days before the injury (Sinha et al., 2002), but even oral intake 3 days before the injury showed positive effects. For example, in an ischemia model in rats, infarct volume decreased when resveratrol was given orally once daily for three days before the injury, but there was no decrease when it was given one hour prior to injury (Inoue et al., 2003). Likewise, when administered intraperitoneally immediately after occlusion and at the time of reperfusion, oxyresveratrol (an analogue of resveratrol) at 10 and 20 mg/kg reduced the infarct volume and, in the range of 10–30 mg/kg, improved neurological outcomes. It also reduced apoptotic cell death and damage to the mitochondria. Similar results in infarct volume reduction were reported by Gao and colleagues (2006) when resveratrol was given seven days before the injury at 50 mg/kg, and by Li and colleagues (2010) when rats were injected with 30 mg/kg of resveratrol intraperitoneally for 6 days before the injury. Li and colleagues (2010) also showed a reduction in neurological deficit scores when evaluated with a neuromotor test two hours after reperfusion. When the release of neurotransmitters was measured, rats that received resveratrol showed lower levels of glutamine and aspartate and higher levels of gamma-aminobutyric acid, glycine, and taurine than control ischemic rats. The excitotoxicity index, measured as excitation versus inhibition (i.e., glutamate × glycine/gamma-aminobutyric acid), was also lower in resveratrol-treated animals than in the injured controls. Resveratrol’s effects on resilience were also observed in younger animals. When administered before injury, resveratrol



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