Platelets regulate neuroinflammation and neuronal functions during brain injury
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AbstractIntroduction. Despite it is widely accepted that inflammation in the central nervous system (CNS) contributes to neurodegenerative diseases such as Alzheimer’s disease (AD) and multiple sclerosis, it is not clear how inflammation in CNS is initiated during neurodegerative process in the absence of infection. It is also not clear whether inflammation in the CNS is beneficial or detrimental in case of AD or traumatic injury. Our laboratory is interested in earliest events of initiation of neuroinflammmation. One of the cells types that have capacity to immediately respond to neurovascular damage are platelets. Platelets are known to respond to а vascular damage, but their role in the neurodegenerative and neuroinflammatory diseases is not well known.

Results. We have previously found that administration of brain lipid rafts induced a massive platelet activation and degranulation. The brain-specific glycolipids (gangliosides) within brain lipid rafts were specifically recognized by the platelets and this recognition occurred during disruption of blood brain barrier, a hallmark of CNS inflammation. We compared inflammatory response in the CNS of wild-type (WT) vs. ST3-/- mice that lack of major brain-specific gangliosides. Our study revealed that level of microglia activation and leukocyte infiltration was substantially lower in ST3-/- animals. In addition, we found that after traumatic injury, ST3 knockout (ST3KO) mice had substantially larger area of damage with dramatic neuronal loss. Interaction of platelets with brain lipid rafts in WT mice resulted in release of serotonin and platelet-activation factor that mediated recruitment of peripheral leukocytes and decreased CNS hemorrhage.

Conclusions. Thus, these studies determined a new role of platelets as “innate immune cells” that directly recognize a neuronal damage and contribute to inflammation in the CNS. Our further studies indicated that interaction of platelets with brain lipid rafts in WT, but not ST3-/- mice resulted in increased growth of axons and formation of new synapses. Collectively all these data indicate the role of platelet-brain lipid raft interactions in induction of protective neuroinflammation that restrict area of damage and promote neuronal repair.
Acceptance Date17/09/2017
All Author(s) ListE. PONOMAREV, M. DUKHINOVA, E. KOPEIKINA, T. VEREMEYKO, I. KUZNETSOVA, A.W.Y. YUNG
Name of ConferenceCell Symposia: Neuro-Immune Axis: Reciprocal Regulation in Development, Health, and Disease
Start Date of Conference17/09/2017
End Date of Conference19/09/2017
Place of ConferenceSitges
Country/Region of ConferenceSpain
Year2017
LanguagesEnglish-United States

Last updated on 2018-30-04 at 11:32