Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats

Yansong Li, Mikulas Chavko, Jessica L. Slack, Bin Liu, Richard M. McCarron, James Ross, Jurandir J. Dalle Lucca

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Blast-induced neurotrauma (BINT) is the signature life threatening injury of current military casualties. Neuroinflammation is a key pathological occurrence of secondary injury contributing to brain damage after blast injury. We have recently demonstrated that blast-triggered complement activation and cytokine release are associated with BINT. Here, we evaluated if administration of the complement inhibitor recombinant human decay-accelerating factor (rhDAF) is beneficial on neuroinflammation and neurodegeneration in a rat model of moderate BINT. Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood-brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI. Result: Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood-brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. Conclusion: These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.

Original languageEnglish (US)
Article number52
JournalActa neuropathologica communications
Volume2
Issue number1
DOIs
StatePublished - Jan 27 2014
Externally publishedYes

Fingerprint

CD55 Antigens
Complement Inactivating Agents
Cytokines
Blood-Brain Barrier
Brain Injuries
Edema
Complement System Proteins
Phosphorylation
Blast Injuries
Complement Activation
Wounds and Injuries

Keywords

  • Blast overpressure
  • Blast-induced neurotrauma
  • Blood-brain barrier
  • Complement activation
  • Decay-accelerating factor
  • Tauopathy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats. / Li, Yansong; Chavko, Mikulas; Slack, Jessica L.; Liu, Bin; McCarron, Richard M.; Ross, James; Dalle Lucca, Jurandir J.

In: Acta neuropathologica communications, Vol. 2, No. 1, 52, 27.01.2014.

Research output: Contribution to journalArticle

Li, Yansong ; Chavko, Mikulas ; Slack, Jessica L. ; Liu, Bin ; McCarron, Richard M. ; Ross, James ; Dalle Lucca, Jurandir J. / Protective effects of decay-accelerating factor on blast-induced neurotrauma in rats. In: Acta neuropathologica communications. 2014 ; Vol. 2, No. 1.
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abstract = "Background: Blast-induced neurotrauma (BINT) is the signature life threatening injury of current military casualties. Neuroinflammation is a key pathological occurrence of secondary injury contributing to brain damage after blast injury. We have recently demonstrated that blast-triggered complement activation and cytokine release are associated with BINT. Here, we evaluated if administration of the complement inhibitor recombinant human decay-accelerating factor (rhDAF) is beneficial on neuroinflammation and neurodegeneration in a rat model of moderate BINT. Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood-brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI. Result: Administration of rhDAF after exposure to moderate blast overpressure (BOP, 120 kPa) mitigated brain injury characterized by neuronal degeneration. rhDAF treatment reduced complement hemolytic activity at 3 hours and tissue complement deposition at 3, 24, and 48 hours as well as systemic and local cytokine release at 24 hours post BOP. Furthermore, rhDAF protected blood-brain barrier (BBB) integrity and reduced cytotoxic edema. Interaction between complement cleavage component, C3a and C3a receptor and tau phosphorylation were also attenuated in rhDAF treated animals at 3 and 24 hours after BOP. Conclusion: These novel findings suggest early complement targeted inhibition as a new therapeutic strategy to decrease neuroinflammation and neurodegeneration after blast TBI.",
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