Am J Pharmacol | Volume 2, Issue 2 | Research Article | Open Access

Targeting the Pyk2/MCU Pathway, Ruthenium Red and Nimodipne Alone and in Combination Evoked NeuroProtective Effect in Experimentally Induced Brain Stroke

Yasmin M Etman2, Amany A Alzokakya1*, Wedad A Hassan2, Ahmed H Eid2 and Azza S Awad1,3

1Department of Pharmacology and Toxicology, Al-Azhar University, Egypt2Department of Pharmacology, National Organization for Drug Control and Research (NODCAR), Egypt3Department of Pharmacology and Toxicology, Ahram Canadian University, Egypt

*Correspondance to: Amany A Alzokakya 

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Mitochondrial dysfunction caused by Ca2+ overload plays an essential role in ischemia associated with brain damage. The proline rich tyrosine kinase 2 (pyk2)/Mitochondrial Calcium Uniporter (MCU) pathway is essential in cerebral ischemic stroke, and is responsible for mitochondrial damage and neuronal degeneration. The present study aimed to investigate the neuroprotective potentials of ruthenium red and nimodipine in brain ischemia induced by Middle Cerebral Artery Occlusion (MCAO). Ruthenium Red (RR), Nimodipine (NMD) and their combination effectively decreased the brain ischemic changes and mitigated the neuronal damage evidenced by reversing the brain histopathological aberrations and decreasing percentage of infraction volume. At the same time, both agents and their combination improved cerebral blood flow through down regulation of Pyk2 and MCU gene expression in brain tissue. They also opposed the inflammatory load via attenuation of brain myeloperoxidase activity, lowered lipid peroxides, NAD(P)H dehydrogenase quinine 1(NQO1) and nitric oxide and boosted the brain glutathione. To the greatest of our knowledge, this is the first study to reveal the neuroprotective effects of RR, NMD and their combination in cerebral brain stroke model.


Ruthenium red; Nimodipine; Middle cerebral artery occlusion; Pyk2/MCU pathway


Etman YM, Alzokakya AA, Hassan WA, Eid AH, Awad AS. Targeting the Pyk2/ MCU Pathway, Ruthenium Red and Nimodipne Alone and in Combination Evoked Neuro-Protective Effect in Experimentally Induced Brain Stroke in Rat. Am J Pharmacol. 2019;2(2):1019 .

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