1H NMR metabolomic profiling elucidated attenuation of neurometabolic alterations by lercanidipine in MCAo model in rats

Abstract

Objectives Stroke is a leading cause of death and disability worldwide with limited therapeutic interventions. The current study explored proton nuclear magnetic resonance spectroscopy ( 1 H NMR)-based metabolomic approach to elucidate the effect of lercanidipine on neurometabolic alterations in transient model of ischaemic stroke in rats. Methods In the present investigation, male Wistar rats were subjected to middle cerebral artery occlusion (MCAo) for 2 h followed by reperfusion using intraluminal filament method. Rats were randomly divided into three groups as vehicle-treated sham control, vehicle-treated MCAo control and lercanidipine-treated MCAo. Vehicle or lercanidipine (0.5 mg/kg, i.p.) was administered 120 min post-reperfusion. The rat brain cortex tissues were isolated 24 h post-MCAo and were investigated by 1 H NMR spectroscopy through perchloric extraction method. Key findings A total of 23 metabolites were altered significantly after cerebral ischaemic-reperfusion injury in MCAo control as compared to sham control rats. Lercanidipine significantly reduced the levels of valine, alanine, lactate, acetate and tyrosine, while N-acetylaspartate, glutamate, glutamine, aspartate, creatine/phosphocreatine, choline, glycerophosphorylcholine, taurine, myo-inositol and adenosine di-phosphate were elevated as compared to MCAo control. Conclusions Present study illustrates effect of lercanidipine on neurometabolic alterations which might be mediated through its antioxidant, anti-inflammatory, vasodilatory and anti-apoptotic property in MCAo model of stroke.

The Combination of Individual Herb of Mi-Jian-Chang-Pu Formula Exerts a Synergistic Effect in the Treatment of Ischemic Stroke in Rats

“…Glutamine was proved possessing anti-inflammatory and antioxidant effects [ 31 ]. In this experiment, glutamine was significantly downregulated in MCAO rats, implied that glutamate metabolism was related to the occurrence of IS, which was also consistent with previous studies [ 32 ].…”

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke

“…Stroke drug treatments were characterized before by reduction of oxidative stress, lowering inflammation, and recovering energy metabolism. 67 , 68 Positive metabolite alterations after drug treatment in stroke models have been reported for glucose, lactate, ATP, and glutathione. 69 , 70 Other metabolites such as NAA have a complex interpretation.…”

Potential Therapeutic Effects of Mi-Jian-Chang-Pu Decoction on Neurochemical and Metabolic Changes of Cerebral Ischemia-Reperfusion Injury in Rats

“…When cerebral infarction occurred, energy metabolism disturbance appeared in the whole brain, resulting in the interruption of mitochondrial metabolism and the reduction of ATP production, which led to the production of lactic acid through anaerobic degradation of glucose. Meanwhile, creatine phosphate, another way of energy storage, was also decomposed into creatine for energy supply [ 42 ]. Once severe cerebral ischemia occurred, the death of neurons and decrease in glucose metabolism appeared one after another, which indicated that energy metabolism disorder was the root cause of cerebral IR injury.…”