TY - JOUR
T1 - Platelets mediate protective neuroinflammation and promote neuronal plasticity at the site of neuronal injury
AU - Dukhinova, Marina
AU - Kuznetsova, Inna
AU - Kopeikina, Ekaterina
AU - Veniaminova, Ekaterina
AU - Yung, Amanda W.Y.
AU - Veremeyko, Tatyana
AU - Levchuk, Kseniia
AU - Barteneva, Natasha S.
AU - Wing-Ho, Kenny Kam
AU - Yung, Wing Ho
AU - Liu, Julia Y.H.
AU - Rudd, John
AU - Yau, Sonata S.Y.
AU - Anthony, Daniel C.
AU - Strekalova, Tatyana
AU - Ponomarev, Eugene D.
N1 - Funding Information:
We wish to thank Ekaterina Biryukova and Yana Venerina for technical assistance for analysis of behaviour tests. The work was supported by the Lo Kwee-Seong Biomedical Research fund ( The Chinese University of Hong Kong ), Health and Medical Research Fund Grant, reference no. 02130636 ( Hong Kong Government, Hong Kong ), and the Research Grant Council-General Research Fund Grant, reference no 14113316 (Hong Kong Government, Hong Kong).
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - CNS repair
KW - Dendritic spines
KW - Glycobiology
KW - Neuroinflammation
KW - Neuronal plasticity
KW - Platelet-derived microparticles
KW - Platelets
KW - Serotonin
KW - Traumatic brain injury
UR - http://www.scopus.com/inward/record.url?scp=85053389611&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2018.09.009
DO - 10.1016/j.bbi.2018.09.009
M3 - Journal article
C2 - 30217533
AN - SCOPUS:85053389611
SN - 0889-1591
VL - 74
SP - 7
EP - 27
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -