Platelets mediate protective neuroinflammation and promote neuronal plasticity at the site of neuronal injury

Brain Behav Immun. 2018 Nov:74:7-27. doi: 10.1016/j.bbi.2018.09.009. Epub 2018 Sep 11.

Abstract

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.

Keywords: CNS repair; Dendritic spines; Glycobiology; Neuroinflammation; Neuronal plasticity; Platelet-derived microparticles; Platelets; Serotonin; Traumatic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / metabolism
  • Blood Platelets / physiology*
  • Brain / metabolism
  • Brain Injuries, Traumatic / physiopathology
  • Disease Models, Animal
  • Encephalitis / metabolism
  • Female
  • Glycolipids / metabolism
  • Glycolipids / physiology
  • Inflammation / metabolism
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / metabolism
  • Neuroimmunomodulation / physiology*
  • Neuronal Plasticity / physiology*
  • Neurons / physiology
  • Platelet Activating Factor / metabolism
  • Platelet Activating Factor / physiology
  • Serotonin / metabolism

Substances

  • Glycolipids
  • Platelet Activating Factor
  • Serotonin