Abstract
We report, for the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI). Acylcarnitines palmitoylcarnitine (AC(16:0)), palmitoleoylcarnitine (AC(16:1)), elaidic carnitine (AC(18:1)) and tetradecanoylcarnitine (AC(14:1)) were detected as early as 3 days post injury, and were present along the lesion margins 7 and 10 days after SCI induced by balloon compression technique in the rat. 3D MSI revealed the heterogeneous distribution of these lipids across the injured spinal cord, appearing well-defined at the lesion margins rostral to the lesion center, and becoming widespread and less confined to the margins at the region located caudally. The assigned acylcarnitines co-localize with resident microglia/macrophages detected along the lesion margins by immunofluorescence. Given the reported pro-inflammatory role of these acylcarnitines, their specific spatial localization along the lesion margin could hint at their potential pathophysiological roles in the progression of SCI.
Highlights
We report, for the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI)
Upon induction of SCI at thoracic segments Th8-Th9, disruption of this distribution is observed at the lesion center and penumbra, leading to the disappearance of high MW signals and generation of low-MW signals in all areas affected by the lesion, i.e., at the lesion site (L) itself as well as in the caudal parts of R1 and rostral parts of C1
Pairwise comparison of spectra taken from the lesion (L) segments at each time point post-SCI reveals that these signals are present at all time points
Summary
For the first time, the detection and specific localization of long-chain acylcarnitines (LC ACs) along the lesion margins in an experimental model of spinal cord injury (SCI) using 3D mass spectrometry imaging (MSI). In addition to mono-therapies, more complex cellular therapies are being suggested carrying several advantages and targeting several SCI-associated conditions such as: to bridge cavities or cysts, to replace dead cells, to create a favorable environment, and to allow axonal regeneration[8,9,10]. None of these provides a total understanding of the injury-inflammatory mechanisms involved in the lesioned spinal cord and proximities that can be used for a temporal and segment-specific target in SCI treatment. The molecular cross-talk occurring among cellular inhabitants at the lesion site and the adjacent segments needs to be investigated for this purpose
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