MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

Hankin, Joseph A.; Farias, Santiago; Barkley, Robert M.; Heidenreich, Kim A.; Frey, Lauren C.; Hamazaki, Kei; Kim, Hee‐Yong; Murphy, Robert C.

doi:10.1007/s13361-011-0122-z

Cited by 114 publications

(126 citation statements)

References 32 publications

Supporting

Mentioning

117

Contrasting

Order By: Relevance

“…Previous works demonstrated that the tissue damage produced during ischemia is accompanied by a deregulation of the Na + /K + -ATPase (or Na + pump) inducing changes in the relative abundance of Na + /K + adducts [27]. In the case of cancer, it is well known that tumor cells are usually in environments with lower pH than healthy tissue, probably owing to their unbalanced metabolism [28,29].…”

Section: Resultsmentioning

confidence: 99%

Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

Fernández

Garate

Lage

et al. 2015

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Abstract. Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl-and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na + adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na + /K + ratios may highlight the necrotic areas while an increase on the number of PEether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na + and K + adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results.

show abstract

Section: Resultsmentioning

confidence: 99%

Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

Fernández

Garate

Lage

et al. 2015

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

show abstract

“…As with the brain PL analyses, we examined total PL levels which showed that while PC, PE, SM, and PI levels were lower in injured mice relative to controls at this 3 mo postinjury time point, only a decrease in PI among injured mice was statistically significant (F (1,20) ϭ21, PϽ0.01; Fig. 8).…”

Section: Plasma Pl Levels Following CCI Tbi At 3 Mo Postexposurementioning

confidence: 99%

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

et al. 2014

View full text Add to dashboard Cite

Phospholipid (PL) abnormalities are observed in the cerebrospinal fluid of patients with traumatic brain injury (TBI), suggesting their role in TBI pathology. Therefore, PL levels were examined in a TBI mouse model that received 1.8 mm deep controlled cortical impact injury or craniectomy only (control). The rotarod and Barnes maze acquisition and probe tests were performed within 2 wk after injury, with another probe test performed 3 mo postinjury. Liquid chromatography/mass spectrometry analyses were performed on lipid extracts from several brain regions and plasma from injured and control mice collected at 3 mo postinjury. Compared to controls, injured mice with sensorimotor and learning deficits had decreased levels of cortical and cerebellar phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels, while hippocampal PC, sphingomyelin and PE levels were elevated. Ether PE levels were lower in the cortices and plasma of injured animals. Polyunsaturated fatty acid-containing PC and PE species, particularly ratios of docosahexaenoic acid (DHA) to arachidonic acid, were lower in the hippocampi and cortices and plasma of injured mice. Given the importance of DHA in maintaining neuronal function and resolving inflammation and of peroxisomes in synthesis of ether PLs, normalizing these PLs may be a useful strategy for treating the chronic pathology of TBI.-Abdullah, L., Evans, J. E., Ferguson, S., Mouzon, B., Montague, H., Reed, J., Crynen, G., Emmerich, T., Crocker, M., Pelot, R., Mullan, M., Crawford, F. Lipidomic analyses identify injury-specific phospholipid changes 3 months after traumatic brain injury. FASEB J. 28, 5311-5321 (2014). www.fasebj.org Key Words: controlled cortical impact ⅐ mass spectrometry ⅐ phosphatidylcholine ⅐ phosphatidylethanolamine ⅐ phosphatidylinositol ⅐ sphingomyelin Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the United States among adults from both the civilian and military populations. Due to the improvements made in military body armor and combat helmets over the past 2 decades, the rate of severe TBI associated with Iraq and Afghanistan deployments has decreased to 1% of the total TBI sustained by military personnel, a rate that is lower than those reported for previous deployments (1-3). Estimates from the U.S. Centers for Disease Control and Prevention suggest that severe TBI remains an important issue in the civilian population. In 2010, 2.5 million admissions to emergency departments were due to TBI (4) contributing to about a third of injury related deaths in the United States. The annual U.S. costs associated with TBI are estimated to be $75 billion, largely attributed to medical care, loss of productivity, and long-term disability (5). Although mild TBI occurs more frequently than severe TBI, the latter has the largest adverse effect on the activities of daily living of injured individuals and accounts for 90% of the total TBI-related medical costs (5). The primary injury is caused by the immediate force of the trauma a...

show abstract

“…MALDI-IMS has been used extensively to study lipids in tissue because IMS can resolve their structures and compositional diversity [32,33]. For example, MALDI-IMS has been used to visualize the heterogeneous distribution of PC species in mouse brains [34], and effects of traumatic brain injury on the differential localization of PCs in rat brains [35]. Furthermore, MALDI-IMS detected alterations in phospholipid zonation in human livers with steatosis or nonalcoholic steatohepatitis (NASH) [36], and MALDI-TOF was used to measure serum lipidomic profiles in patients with NASH [37].…”

Section: Introductionmentioning

confidence: 99%

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Yalçın¹,

Nunez²,

Cornett³

2015

J Drug Alcohol Res

View full text Add to dashboard Cite

Background. Ethanol, tobacco-specific nitrosamine ketone (NNK), and ethanol+NNK exposures cause steatohepatitis, suggesting that smoking can be a cofactor in alcoholic liver disease. Study design. We used MALDI-TOF imaging mass spectrometry (IMS) to characterize hepatic lipid profiles in steatohepatitis caused by ethanol, NNK, and ethanol+NNK. Results. Ethanol, NNK, and ethanol+NNK increased levels and altered the profiles of hepatic phospholipids. Ethanol caused striking accumulations of m/z 932.7 phosphatidylinositol (PI). NNK increased hepatic levels of PIs with m/z's of 934.8, 960.8, and 962.7. Relative abundance of PIs with m/z's of 857.9 or 883.7 increased progressively from control to NNK, then ethanol, and finally ethanol+NNK, indicating differential and additive effects of these exposures. In contrast, no differences occurred with respect to phosphatidylethanolamine (m/z 766.9), phosphatidylserine (m/z 810.9) or PIs with m/z of 960.8 or 962.7. Principal component analysis generated distinct exposure-related hepatic lipid profiles. Conclusion. MALDI-IMS could serve as a complementary diagnostic aid for differentiating underlying causes of steatohepatitis.

show abstract

MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

Cited by 114 publications

References 32 publications

Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

Lipidomic analyses identify injury‐specific phospholipid changes 3 mo after traumatic brain injury

Differential Lipid Profiles in Experimental Steatohepatitis: Role for Imaging Mass Spectrometry as a Diagnostic Aid

Contact Info

Product

Resources

About