Site-targeted complement inhibition by a complement receptor 2-conjugated inhibitor (mTT30) ameliorates post-injury neuropathology in mouse brains

Megan C. Rich, Chesleigh N. Keene, Miriam D. Neher, Krista Johnson, Zhao Xue Yu, Antoine Ganivet, V. Michael Holers, Philip F. Stahel

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Intracerebral complement activation after severe traumatic brain injury (TBI) leads to a cascade of neuroinflammatory pathological sequelae that propagate host-mediated secondary brain injury and adverse outcomes. There are currently no specific pharmacological agents on the market to prevent or mitigate the development of secondary cerebral insults after TBI. A novel chimeric CR2-fH compound (mTT30) provides targeted inhibition of the alternative complement pathway at the site of tissue injury. This experimental study was designed to test the neuroprotective effects of mTT30 in a mouse model of closed head injury. The administration of 500 μg mTT30 i.v. at 1 h, 4 h and 24 h after head injury attenuated complement C3 deposition in injured brains, reduced the extent of neuronal cell death, and decreased post-injury microglial activation, compared to vehicle-injected placebo controls. These data imply that site-targeted alternative pathway complement inhibition may represent a new promising therapeutic avenue for the future management of severe TBI.

Original languageEnglish (US)
Pages (from-to)188-194
Number of pages7
JournalNeuroscience Letters
Volume617
DOIs
StatePublished - Mar 23 2016
Externally publishedYes

Keywords

  • CR2-conjugated pharmacological compounds
  • Neuroinflammation
  • Secondary brain injury
  • Site-targeted complement inhibition
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)

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