Medicines Discovery Catapult, 35 Mereside Alderley Park, Macclesfield SK10 4ZF, UK.
The Photon Science Institute, Department of Chemistry, The University of Manchester, Manchester M13 9PL, UK.
Int J Mol Sci. 2024 Nov 8;25(22):12032. doi: 10.3390/ijms252212032.
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.
神经炎症是一种与多种病理学相关的复杂生物学过程，通常需要更好地理解，以便开发新的、有针对性的治疗干预措施。在这种情况下，多模态质谱成像（MSI）已被用于描述神经炎症中的分子变化，以发现其他技术无法发现的生物标志物。在这项研究中，包括生物活性脂质在内的分子在接受脂多糖（LPS）治疗的大鼠的大脑炎症区域被检测到。这些检测到的脂质可能作为免疫反应的炎症介质发挥作用。我们发现 N-酰基-磷脂乙醇胺（NAPE）物质在炎症区域积累。这些脂质的存在可能与内源性大麻素（eCB）信号系统有关，在损伤部位的小胶质细胞中介导抗炎反应，以平衡促炎和支持神经元保护。此外，多不饱和脂肪酸（PUFAs），特别是 n-3 和 n-6 种类，在 LPS 注射部位观察到积累。PUFAs 与抗炎介质直接相关，可解决炎症。最后，酰基辅酶 A 物质在炎症区域周围积累。这些分子的积累可能是由于β-氧化循环不足。
