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Neuroinflammation is a complex biological process related to a variety of pathologies, often requiring better understanding in order to develop new, targeted therapeutic interventions. Within this context, multimodal Mass Spectrometry Imaging (MSI) has been used to characterise molecular changes in neuroinflammation for biomarker discovery not possible to other techniques. In this study, molecules including bioactive lipids were detected across inflamed regions of the brain in rats treated with lipopolysaccharide (LPS). The detected lipids may be acting as inflammatory mediators of the immune response. We identified that N-acyl-phosphatidylethanolamine (NAPE) species accumulated in the inflamed area. The presence of these lipids could be related to the endocannabinoid (eCB) signalling system, mediating an anti-inflammatory response from microglial cells at the site of injury to balance pro-inflammation and support neuronal protection. In addition, polyunsaturated fatty acids (PUFAs), specifically n-3 and n-6 species, were observed to accumulate in the area where LPS was injected. PUFAs are directly linked to anti-inflammatory mediators resolving inflammation. Finally, acylcarnitine species accumulated around the inflammation region. Accumulation of these molecules could be due to a deficient β-oxidation cycle. [ABSTRACT FROM AUTHOR]

Following from our previous Letter on this topic, this Article reports a detailed study of time-of-flight-secondary ion mass spectrometry (TOF-SIMS) positive ion spectra generated from a set of model biocompounds (arginine, trehalose, DPPC, and angiotensin II) by water cluster primary ion beams in comparison to argon cluster beams over a range of cluster sizes and energies. Sputter yield studies using argon and water beams on arginine and Irganox 1010 have confirmed that the sputter yields using water cluster beams lie on the same universal sputtering curve derived by Seah for argon cluster beams. Thus, increased ion yield using water cluster beams must arise from increased ionization. The spectra and positive ion signals observed using cluster beams in the size range from 1 000 to 10 000 and the energy range 5-20 keV are reported. It is confirmed that water cluster beams enhance proton related ionization over against argon beams to a significant degree such that enhanced detection sensitivities from 1 μm2 in the region of 100 to 1 000 times relative to static SIMS analysis with Ar2000 cluster beams appear to be accessible. These new studies show that there is an unexpected complexity in the ionization enhancement phenomenon. Whereas optimum ion yields under argon cluster bombardment occur in the region of E/n ⩾ 10 eV (where E is the beam energy and n the number of argon atoms in the cluster) and fall rapidly when E/n < 10 eV; for water cluster beams, ion yields increase significantly in this E/n regime (where n is the number of water molecules in the cluster) and peak for 20 keV beams at a cluster size of 7 000 or E/n ∼3 eV. This important result is explored further using D2O cluster beams that confirm that in this low E/n regime protonation does originate to a large extent from the water molecules. The results, encouraging in themselves, suggest that for both argon and water cluster beams, higher energy beams, e.g., 40 and 80 keV, would enable larger cluster sizes to be exploited with significant benefit for ion yield and hence analytical capability. [ABSTRACT FROM AUTHOR]

Rationale: To discover the degree to which water-containing cluster beams increase secondary ion yield and reduce the matrix effect in time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging of biological tissue., Methods: The positive SIMS ion yields from model compounds, mouse brain lipid extract and mouse brain tissue together with mouse brain images were compared using 20 keV C60(+), Ar2000(+), water-doped Ar2000(+) and pure (H2O)6000(+) primary beams., Results: Water-containing cluster beams where the beam energy per nucleon (E/nucleon) ≈ 0.2 eV are optimum for enhancing ion yields dependent on protonation. Ion yield enhancements over those observed using Ar2000(+) lie in the range 10 to >100 using the (H2 O)6000 (+) beam, while with water-doped (H2O)Ar2000(+) they lie in the 4 to 10 range. The two water-containing beams appear to be optimum for tissue imaging and show strong evidence of increasing yields from molecules that experience matrix suppression under other primary beams., Conclusions: The application of water-containing primary beams is suggested for biological SIMS imaging applications, particularly if the beam energy can be raised to 40 keV or higher to further increase ion yield and enhance spatial resolution to ≤1 µm., (© 2015 The Authors. Rapid Communications in Mass Spectrometry Published by John Wiley & Sons Ltd.)