Nordihydroguaiaretic Acid (NDGA) Promotes Functional Recovery after Transient Focal Cerebral Ischemia in Rats

Nordihydroguaiaretic acid (NDGA), isolated from Larrea tridentata, is a lipoxygenase (LOX) inhibitor with potent antioxidant activities. It has been demonstrated that NDGA shows protective effect in the acute phase of stroke. However, the effect of NDGA on the long-term outcomes after focal cerebral ischemia is not clear. The current study was designed to investigate the role of NDGA in a transient ischemia rat model to determine whether it promotes functional recovery and the underlying mechanism. The results showed that NDGA improved functional outcomes as measured by adhesive-removal and foot fault test. NDGA significantly promotes both neurogenesis and angiogenesis 28 days after ischemia and reperfusion. NDGA suppressed the expression of semaphorin 3A (Sema3A), whereas exogenous 12-HETE attenuated this effect. In conclusion, these results suggest that NDGA's protective effect on the functional recovery is mediated by the suppression of Sema3A pathway. This effect is probably due to its 12-LOX inhibitor property.