Matrix‐assisted laser desorption/ionization imaging mass spectrometry of intraperitoneally injected danegaptide (ZP1609) for treatment of stroke‐reperfusion injury in mice

Wang, Jasmine S.-H.; Freitas‐Andrade, Moises; Bechberger, John F.; Naus, Christian C.; Yeung, Ken K.‐C.; Whitehead, Shawn N.

doi:10.1002/rcm.8115

Cited by 11 publications

(4 citation statements)

References 36 publications

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“…The increase in signal intensity indicates successful transport of danegaptide even under ischemic conditions. This is consistent with a recent study showing that danegaptide crosses the BBB, under different stroke models, when IP injected [44].…”

Section: Maldi Ims Was Able To Detect the Presence Of Danegaptide In supporting

confidence: 93%

“…However, delivery of pharmacological agents in the brain are a challenge due to the tight BBB. A previous study demonstrated that IP-injected danegaptide crosses the BBB and was clearly detected in ischemic mouse brain tissue [44]. Similarly, using MALDI-IMS techniques, we observed danegaptide in brain parenchyma in mice subjected to ischemia/reperfusion.…”

Section: Discussionsupporting

confidence: 78%

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Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice

et al. 2020

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Ischemic stroke is a complex and devastating event characterized by cell death resulting from a transient or permanent arterial occlusion. Astrocytic connexin43 (Cx43) gap junction (GJ) proteins have been reported to impact neuronal survival in ischemic conditions. Consequently, Cx43 could be a potential target for therapeutic approaches to stroke. We examined the effect of danegaptide (ZP1609), an antiarrhythmic dipeptide that specifically enhances GJ conductance, in two different rodent stroke models. In this study, danegaptide increased astrocytic Cx43 coupling with no significant effects on Cx43 hemichannel activity, in vitro. Using matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) the presence of danegaptide within brain tissue sections were detected one hour after reperfusion indicating successful transport of the dipeptide across the blood brain barrier. Furthermore, administration of danegaptide in a novel mouse brain ischemia/reperfusion model showed significant decrease in infarct volume. Taken together, this study provides evidence for the therapeutic potential of danegaptide in ischemia/reperfusion stroke.

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Section: Maldi Ims Was Able To Detect the Presence Of Danegaptide In supporting

confidence: 93%

Section: Discussionsupporting

confidence: 78%

Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice

et al. 2020

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“…Drug distribution monitoring is one of the main applications of MSI in CNS injury and neurodegenerative diseases. To monitor the localization of a therapeutic candidate, Danegaptide (ZP1609), Wang et al (2018) performed MSI experiments using MALDI-TOF MSI instrumentation to visually detect ZP1609 distribution in mouse brain tissue post transient middle cerebral artery occlusion. Images showed the ability of ZP1609 to penetrate the BBB and localize in the injury site.…”

Section: Lipid Msi Application In Other Cns-related Injuries/disease ...mentioning

confidence: 99%

Neurotrauma investigation through spatial omics guided by mass spectrometry imaging: Target identification and clinical applications

Mallah

Zibara

Kerbaj

et al. 2021

Mass Spectrometry Reviews

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Traumatic brain injury (TBI) represents one of the major public health concerns worldwide due to the increase in TBI incidence as a result of injuries from daily life accidents such as sports and motor vehicle transportation as well as militaryrelated practices. This type of central nervous system trauma is known to predispose patients to several neurological disorders such as Parkinson's disease, Alzheimer's disease, chronic trauamatic encephalopathy, and age-related Dementia. Recently, several proteomic and lipidomic platforms have been applied on different TBI studies to investigate TBI-related mechanisms that have broadened our understanding of its distinct neuropathological complications. In this study, we provide an updated comprehensive overview of the current knowledge and novel perspectives of the spatially resolved microproteomics and microlipidomics approaches guided by mass spectrometry imaging used in TBI studies and its applications in the neurotrauma field. In this regard, we will discuss the use of the spatially resolved microproteomics and assess the different microproteomic sampling methods such as laser capture microdissection, parafilm assisted microdissection, and liquid microjunction extraction as accurate and precise techniques in the field of neuroproteomics. Additionally, we will highlight lipid profiling applications and their prospective potentials in characterizing molecular processes involved in the field of TBI. Specifically, we will discuss the phospholipid metabolism acting as a precursor for proinflammatory molecules such as eicosanoids. Finally, we will survey the current state of spatial neuroproteomics and microproteomics applications and present the various studies highlighting their findings in these fields.

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“…SOMs can produce matrix-related signals, such as molecule ions, clusters, and fragments, which hinder noise-free (MALDI silent) measurements below m / z = 1000. While such cluster signals can be used as internal standards (lock mass) to avoid mass shifts, MALDI-silent matrix systems are preferable: they allow us to freely choose sample-specific standards, and furthermore, the occurrence of multiple strong matrix-related signals can be detrimental for certain measurements, especially when analyzing low-molecular-weight compounds (LMWCs), e.g., in drug assays or disease research. − Also, SOMs often exhibit low stability in high vacuum (HV) (∼10 – mbar) due to their low molar mass, which can result in an inhomogeneous matrix layer during long-term MALDI MSI measurements . A number of developments on the instrument side were reported in recent years, most notably innovations moving away from the HV centered instrumentation: For example, modern trapped ion mobility spectrometry (TIMS), orbitrap, and Fourier transform ion cyclotron resonance (FTICR) instruments allow a confident assignment of LMWCs under a subatmospheric (subAP) ion source pressure, preventing the sublimation of non-vacuum-stable matrices or analytes. − Moreover, the detection and accurate identification of metabolites in complex tissue samples are performed using high-mass resolving power mass spectrometers, such as FTICR that require parametrical optimization and longer acquisition time, which is a setback especially in clinical and routine settings based on MSI procedures. , However, recently, a subspace method was proposed to accelerate the data acquisition in FTICR MSI .…”

Section: Introductionmentioning

confidence: 99%

Polymerization as a Strategy to Improve Small Organic Matrices for Low-Molecular-Weight Compound Analytics with MALDI MS and MALDI MS Imaging

Horatz

Giampà

Qiao

et al. 2021

ACS Appl. Polym. Mater.

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Matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) and the corresponding visualizing technique MALDI MS imaging (MSI) are potent and widely used analytical methods in medical and pathological research. In recent years, the investigation of low-molecular-weight compounds (LMWCs) such as metabolites has moved increasingly into the focus. MALDI techniques require a matrix system, and small organic matrices (SOMs) are commonly used. While SOMs offer multiple advantages, such as broad analyte scopes and high ionization efficiencies, they also suffer from drawbacks, e.g., strong background interferences in the low-mass area (m/z < 1000) and low vacuum stability, which is particularly detrimental for LMWC analytics with high vacuum (HV) MALDI MS and MSI. Here, we apply polymerization as a strategy to alleviate these drawbacks while retaining the multiple advantages of SOMs. Vinyl groups were introduced to two SOMs, the state-of-the-art positive mode matrix 2,5-dihydroxybenzoic acid (DHB) as well as one of the few known dual polarity mode matrices, 7-methoxy-1-methyl-9H-pyrido[3,4-b]indole (harmine), and radical polymerization was performed to obtain polyethylene-based P(SOMs) carrying the corresponding SOMs as side chains. Compared to the corresponding SOMs, the synthesized P(SOMs) maintain optical properties in the solid state and have competitive performances regarding analyte scopes, ionization efficiencies, and dual polarity mode suitability. Additionally, both P(SOMs) are HV stable (∼10 −7 mbar) and reveal no background interferences in the low-mass area (MALDI-silent). To assess a potential application in a clinical workflow, the P(SOMs) were applied on breast cancer xenografts and MALDI MSI measurements were carried out, demonstrating their ability to produce and spatially resolve positive and negative tissue-related ions directly from the cancer tissue. Polymerization is shown to be a promising strategy to make state-of-the-art SOMs MALDI silent and vacuum stable and yield easily handled matrices for clinical workflows.

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Matrix‐assisted laser desorption/ionization imaging mass spectrometry of intraperitoneally injected danegaptide (ZP1609) for treatment of stroke‐reperfusion injury in mice

Cited by 11 publications

References 36 publications

Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice

Danegaptide Enhances Astrocyte Gap Junctional Coupling and Reduces Ischemic Reperfusion Brain Injury in Mice

Neurotrauma investigation through spatial omics guided by mass spectrometry imaging: Target identification and clinical applications

Polymerization as a Strategy to Improve Small Organic Matrices for Low-Molecular-Weight Compound Analytics with MALDI MS and MALDI MS Imaging

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