Protective Effects of Curcumin and Menthol in Rat Models of Global Cerebral Ischemia: A Comparative Study of Combined and Separate Treatments

Objective Global cerebral ischemia (GCI) is a critical condition that arises in events such as cardiac arrest, leading to memory impairment and neuronal loss. The hippocampus is particularly susceptible to ischemic injury. Menthol (ME) and curcumin (CUR) are natural compounds with reported neuroprotective properties, including antioxidant and anti‐inflammatory effects. This study investigated their neuroprotective effects alone and in combination with GCI. Methods 50 Male Wistar rats were randomly assigned to five groups: Sham, GCI, GCI + CUR (100 mg/kg), GCI + ME (100 mg/kg), and GCI + CUR + ME (100 mg/kg each). GCI was induced by bilateral common carotid artery occlusion for 20 min. Treatment was administered intragastrically 30 min post‐ischemia. Short‐term spatial memory was evaluated using the Y‐maze test. The hippocampal CA1 region was assessed stereologically. Also, antioxidant enzyme activities were measured. Results The GCI + CUR + ME group showed a higher alternation percentage than other treatment groups, indicating enhanced memory retention. Stereological analysis revealed that the GCI + CUR + ME group had significantly greater hippocampal CA1 volume and pyramidal neuron count than the other groups. On the other hand, the CUR group did not show a significant difference from the GCI group for antioxidant activity, while the GCI + CUR + ME group showed the highest antioxidant activity compared to the other treatment groups. Conclusion The combination of CUR and ME offers superior neuroprotection compared to individual treatments, mitigating memory deficits, preserving hippocampal structure, and enhancing antioxidant responses in a rat model of GCI. These findings highlight the potential of CUR and ME as therapeutic agents for ischemic brain injury.