Lipid Changes Associated with Traumatic Brain Injury Revealed by 3D MALDI-MSI

Abstract

Traumatic brain injury (TBI) is a major cause of death and disability in children and young adults worldwide according to the World Health Organization (WHO). The emergence of mass-spectrometry-based techniques, such as MALDI-MSI, has allowed the monitoring and visualization of changes post injury, providing a global picture of the impact of TBI on different classes of molecules in a single study. In this work, we show the ability to track lipid changes post-TBI by three-dimensional matrix-assisted laser desorption/ionization-mass-spectrometry imaging (MALDI-MSI). Controlled cortical impact (CCI) was induced on adult male rats resulting in direct mechanical injury to the cortical tissue on the right ipsilateral hemisphere of the brain. Images of lipid distribution in coronally sectioned injured brains were acquired using a high-resolution mass spectrometer (MALDI-LTQ-Orbitrap-XL). Results reveal unique lipid signatures for the injured cortical tissue, which further segregate into two subgroups of injury (lesion interior and lesion exterior). Although both subgroups show different profiles from that of the noninjured cortical tissue, the lesion interior is more similar to the ventricular system than the lesion exterior. For example, m/ z 725.56 showed expression in both injured tissue and the ventricular system, whereas m/ z 856.59 (phosphatidylcholine 42:9) is uniquely expressed in injured tissue. On the other hand, m/ z 797.59 (also a phosphatidylcholine) showed unique expression to the ventricular system and not to the injured cortical tissue. Our results can help in further monitoring and identifying lesion-specific lipids in a 3D manner to obtain a better understanding and visualization of molecular and cellular events occurring post-TBI.

Experimental and Data Analysis Considerations for Three-Dimensional Mass Spectrometry Imaging in Biomedical Research

“…Lipid changes upon traumatic brain injury were investigated in rat brain with 3D MALDI-MSI to gain more understanding of the biochemical alterations caused by this neurological damage that is a major cause of death and disability in children and young adults [47]. The researchers obtained rat brain tissue sections every 200-250 μm covering the entire area of the cortical-impact injury.…”

“…This is often performed manually by using either anatomical features in optical images that are already aligned to the MS images [68,69] or well-structured MS images to spatially align the consecutive MSI slices (Fig. 5b, c) [47,48]. These approaches are only suitable for tissues with well-defined and visible structures in the optical or MS images.…”

Monitoring the three‐dimensional distribution of endogenous species in the lungs by matrix‐assisted laser desorption/ionization mass spectrometry imaging

“…Later examples monitored the 3D distribution of peptides and proteins in the substantia nigra and interpeduncular nucleus 6 . Proteins have also been visualized in a mouse brain tumor which were co‐registered with MRI data, 7 as were lipids associated with traumatic brain injury 8 and recently lipids in medulloblastoma metastasis 9 . The 3D distribution of peptides and lipids has even been visualized in a crab brain 10 .…”

Defining New Research Questions and Protocols in the Field of Traumatic Brain Injury through Public Engagement: Preliminary Results and Review of the Literature

“…Animal models analysing the microscopic and cellular effects of TBI [28–30] have been conducted; however, these have limited application because they do not necessarily translate accurately to humans and human data remain scarce [31]. Brain tissue sampling outside of tumour surgeries has been done very occasionally, with Harish et al [32] obtaining intraoperative open biopsy samples from 26 patients who had sustained TBI and correlating them to CT scans and Pyykkö et al [33] obtaining cortical brain biopsies using a biopsy needle from 102 patients with normal pressure hydrocephalus (NPH).…”