Sangeetha Gupta1, Uma Sharma2, Naranamangalam R Jagannathan2, Yogendra Kumar Gupta3. 1. Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India. 2. Department of NMR & MRI Facility, All India Institute of Medical Sciences, New Delhi, India. 3. All India Institute of Medical Sciences, Bhopal, India.
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.
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.