Centre for Neuroscience and Trauma. Blizard Institute. Queen Mary University of London, E1 2AT London, United Kingdom.
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla-Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41012 Sevilla, Spain.
Sci Rep. 2017 Jan 27;7:41689. doi: 10.1038/srep41689.
Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galectin-3. In this study, using a controlled cortical impact (CCI) model of head injury, we show a large increase in the expression of galectin-3 in microglia and also an increase in the released form of galectin-3 in the cerebrospinal fluid (CSF) 24 h after head injury. We report that galectin-3 can bind to TLR-4, and that administration of a neutralizing antibody against galectin-3 decreases the expression of IL-1β, IL-6, TNFα and NOS2 and promotes neuroprotection in the cortical and hippocampal cell populations after head injury. Long-term analysis demonstrated a significant neuroprotection in the cortical region in the galectin-3 knockout animals in response to TBI. These results suggest that following head trauma, released galectin-3 may act as an alarmin, binding, among other proteins, to TLR-4 and promoting inflammation and neuronal loss. Taking all together, galectin-3 emerges as a clinically relevant target for TBI therapy.
创伤性脑损伤（TBI）目前是西方社会发病率和生活质量下降的主要原因，欧洲每年估计有 250 万人受到影响，这表明需要在 TBI 治疗方面取得进展。在 TBI 后的 24 小时内，几种炎症反应因子上调，包括凝集素半乳糖凝集素-3。在本研究中，我们使用皮质撞击（CCI）颅脑损伤模型，显示在颅脑损伤后 24 小时，小胶质细胞中半乳糖凝集素-3的表达大量增加，脑脊液（CSF）中半乳糖凝集素-3的释放形式也增加。我们报告半乳糖凝集素-3可以与 TLR-4 结合，并且施用针对半乳糖凝集素-3 的中和抗体可降低 IL-1β、IL-6、TNFα 和 NOS2 的表达，并在颅脑损伤后促进皮质和海马细胞群体的神经保护。长期分析表明，在 TBI 中，半乳糖凝集素-3 敲除动物的皮质区域有明显的神经保护作用。这些结果表明，头部外伤后，释放的半乳糖凝集素-3 可能作为警报素发挥作用，与 TLR-4 等蛋白结合，促进炎症和神经元丧失。综上所述，半乳糖凝集素-3 是 TBI 治疗的一个有临床意义的靶点。
