Gender-specific metabolic responses in focal cerebral ischemia of rats and Huang-Lian-Jie-Du decoction treatment

Abstract

This study aims to explore gender-specific metabolic differences in ischemic stroke and the protective effect of HLJDD using NMR-based metabolomics techniques. A unilateral middle cerebral artery occlusion (MCAO) rat model was established to achieve cerebral ischemia. Rats were orally administrated with the extract of Huang-Lian-Jie-Du decoction once a day for ten consecutive days to study its therapeutic effect. A ¹H NMR-based metabolomics approach combined with pattern recognition approaches was applied to explore gender-specific metabolic profiling of serum, cerebrum and cerebellum extracts. Oxidative stress, energy metabolism, fat and amino acid metabolism were significantly perturbed in male MCAO rats, while only oxidative stress and amino acid metabolism were perturbed in female MCAO rats. These results complemented with neurobehavioral evaluations, cerebral infarct assessments, biochemical evaluations, histological inspections and immunohistochemistry observations strongly demonstrated that gender plays an important role in the process of neuronal damage triggered by cerebral ischemia-reperfusion injury, and female rats are more resistant to ischemic stroke than male rats. Furthermore, HLJDD was found to treat ischemic stroke in a gender dependent manner and females gain a relatively greater benefit than males from HLJDD therapy. This study built a substantial basis for further systematic study on the underlying mechanisms involved in these gender differences in ischemic stroke. These findings also highlight the need to take gender differences into account in the treatment of stroke and the development of its therapy strategies.