Abstract 2675: Acute Curcumin Treatment Reduces Cerebrovascular Injury and Neurological Deficit in Stroked Type 2 Diabetic Rats

Abstract

Background: Curcumin, a derivative of the rhizome Curcuma longa , has antioxidant, anti-inflammatory, and anti-apoptotic properties that make it an attractive potential threrapeutic agent for acute ischemic stroke. Studies using curcumin have shown that it provides neuroprotection when administered prior to focal cerebral ischemia or within 30 min to 1h after middle cerebral artery occlusion (MCAO) in normoglycemic animals. We previously reported that 3 h MCAO followed by 21 h reperfusion induces greater edema, hemorrhage, and neurological deficits in type 2 diabetic rats when compared to normoglycemic controls. Therefore, the goal of this study was to test the hypothesis that curcumin, when administered at recanalization, will decrease neurovascular injury, incidence of bleeding, and improve functional outcome in diabetic rats. Methods: Focal ischemia was induced by 3 h MCAO and 21 h reperfusion in sham, untreated, and curcumin-treated groups (n=5-7 per group). A single dose of curcumin (250 mg/kg, i.p.) or vehicle (EtOH + ethyl oleate) was administered at recanalization in control or diabetic (Goto-Kakizaki) rats. Percent (%) infarct, edema ratio (edema/infarct), and incidence of macroscopic bleeding was assessed in all groups. Neurological tests were performed at baseline and 23 h after MCAO to assess locomotor ability (beam walk), grip strength, and the presence or absence of postural reflexes (circling, resistance to push, forearm flexion, and hindlimb extension). Results: Within the untreated groups, % infarct was greater in controls (57.7±5.8% vs. 9.1±1.0%), while edema ratio was greater in diabetic animals (1.8±0.2 vs. 0.2±0.03). Bleeding was present in the ischemic hemispheres of all diabetic rats and in 43% of the controls. Compared to controls, neurological deficits were greater in diabetic animals after focal ischemia (p<0.05). Curcumin reduced % infarct in controls (30.0±9.9% vs. 9.8±1.8%) and improved edema ratio in diabetic rats (0.7±0.05 vs. 0.2±0.04). Curcumin also reduced the incidence of bleeding in both control and diabetic animals (20% vs. 50%). Incidence of pathological postural reflexes in both control and diabetic animals was decreased following curcumin treatment however it did not improve beam walk scores or grip strength in either group (p<0.05). Vehicle-treated animals were similar to untreated controls at all endpoints. Conclusion: Curcumin provides protection against infarct in normoglycemic animals and vascular protection in diabetic animals when administered at recanalization, suggesting that its use as a therapeutic agent at this clinically relevant time point may be beneficial in both groups but through different mechanisms. Additional long-term studies are needed to determine whether acute curcumin treatment at recanalization is sufficient to improve locomotor ability and grip strength deficits beyond 24 h post-MCAO.