Abstract
Dl-3-n-butylphthalide (NBP) is a drug that is used in the treatment of ischaemic stroke. However, to the best of our knowledge, there are no systematic studies investigating the effects of dl-3-n-butylphtalide on the brain metabolism of small molecules. In this study, we first investigated the effects of dl-3-n-butylphthalide on the spatial distribution of small molecules in the brains of rats with permanent middle cerebral artery occlusion (pMCAO) using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI–TOF–MS) imaging. After pMCAO modelling or a sham operation, rats were given four mg/kg of dl-3-n-butylphthalide through the caudal vein or saline once a day for nine days. The degree of neurological deficit in rats was evaluated using the modified neurological severity score (mNSS). MALDI–TOF–MS imaging was used to observe the content and distribution of small molecules related to metabolism during focal cerebral ischaemia. Multiple reaction monitoring (MRM) mode with liquid chromatography tandem mass spectrometry (LC–MS/MS) was used to verify the results obtained from MALDI–TOF–MS imaging. These small molecules were found to be involved in glucose metabolism, ATP metabolism, the glutamate–glutamine cycle, malate aspartate shuttle, oxidative stress, and inorganic ion homeostasis. Of the 13 metabolites identified by MALDI–TOF–MS imaging, seven compounds, ATP, ADP, AMP, GMP, N-acetylaspartic acid, ascorbic acid and glutathione, were further validated by LC–MS/MS. Taken together, these results indicate that dl-3-n-butylphthalide significantly improved ATP metabolism, level of antioxidants, and sodium-potassium ion balance in a rat model of pMCAO.
Highlights
A stroke leads to a sudden onset of cerebral circulation disorders that are primarily caused by cerebral vascular thrombosis, rupture of blood vessels, and inadequate blood or oxygen supply in brain tissue [1]
Our aim was to determine whether our dl-3-nwas to determine whether dl-3-n-butylphthalide, a common anti-stroke drug that is clinically used butylphthalide, a common anti-stroke drug that is clinically used in China, could improve thesein
The Kaplan–Meier analysis indicated a difference in the survival rate requirement of statistical significance at p < 0.05 (Supplementary Figure S1 and Supplementary Table between the treated groups vs. the permanent middle cerebral artery occlusion (pMCAO) group, but this difference did not meet the requirement of statistical significance at p < 0.05 (Supplementary Figure S1 and Supplementary Table S1)
Summary
A stroke leads to a sudden onset of cerebral circulation disorders that are primarily caused by cerebral vascular thrombosis, rupture of blood vessels, and inadequate blood or oxygen supply in brain tissue [1]. With the improvement in people’s living standards and ageing population, strokes have become a serious threat to human health, with a high incidence rate, high recurrence rate, Int. J. 2017, 18, 2451; doi:10.3390/ijms18112451 www.mdpi.com/journal/ijms Int. Int.J. J.Mol
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