School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin N.T., Hong Kong.
Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL 6229ER, Maastricht, Netherlands; Institute of General Pathology and Pathophysiology, Baltiiskaya str, 8, Moscow, 125315, Russia; Sechenov First Moscow State Medical University, Institute of Molecular Medicine, Laboratory of Psychiatric Neurobiology, Trubetskaya Street 8-2, 119991, Moscow, Russia.
Brain Behav Immun. 2018 Nov;74:7-27. doi: 10.1016/j.bbi.2018.09.009. Epub 2018 Sep 11.
It is generally accepted that inflammation within the CNS contributes to neurodegeneration after traumatic brain injury (TBI), but it is not clear how inflammation is initiated in the absence of infection and whether this neuroinflammation is predominantly beneficial or detrimental. We have previously found that brain-enriched glycosphingolipids within neuronal lipid rafts (NLR) induced platelet degranulation and secretion of neurotransmitters and pro-inflammatory factors. In the present study, we compared TBI-induced inflammation and neurodegeneration in wild-type vs. St3gal5 deficient (ST3) mice that lack major CNS-specific glycosphingolipids. After TBI, microglial activation and CNS macrophage infiltration were substantially reduced in ST3 animals. However, ST3 mice had a larger area of CNS damage with marked neuronal/axonal loss. The interaction of platelets with NLR stimulated neurite growth, increased the number of PSD95-positive dendritic spines, and intensified neuronal activity. Adoptive transfer and blocking experiments provide further that platelet-derived serotonin and platelet activating factor plays a key role in the regulation of sterile neuroinflammation, hemorrhage and neuronal plasticity after TBI.
人们普遍认为，中枢神经系统内的炎症会导致创伤性脑损伤（TBI）后的神经退行性变，但目前尚不清楚在没有感染的情况下炎症是如何引发的，以及这种神经炎症主要是有益还是有害。我们之前发现，神经元脂筏（NLR）内富含脑的糖脂会诱导血小板脱颗粒和神经递质及促炎因子的分泌。在本研究中，我们比较了野生型 vs. ST3gal5 缺陷（ST3）小鼠（缺乏主要中枢神经系统特异性糖脂）的 TBI 诱导炎症和神经退行性变。TBI 后，ST3 动物的小胶质细胞活化和中枢神经系统巨噬细胞浸润明显减少。然而，ST3 小鼠的中枢神经系统损伤面积更大，伴有明显的神经元/轴突丢失。血小板与 NLR 的相互作用刺激神经突生长，增加 PSD95 阳性树突棘的数量，并增强神经元活性。过继转移和阻断实验进一步表明，血小板衍生的 5-羟色胺和血小板激活因子在 TBI 后无菌性神经炎症、出血和神经元可塑性的调节中起关键作用。
