Acute intranasal osteopontin treatment in male rats following TBI increases the number of activated microglia but does not alter lesion characteristics

Amandine Jullienne, Mary Hamer, Elizabeth Haddad, Alexander Morita, Peter Gifford, Richard Hartman, William J. Pearce, Jiping Tang, John H. Zhang, Andre Obenaus

Research output: Contribution to journalArticlepeer-review

Abstract

Intranasal recombinant osteopontin (OPN) has been shown to be neuroprotective in different models of acquired brain injury but has never been tested after traumatic brain injury (TBI). We used a model of moderate-to-severe controlled cortical impact in male adult Sprague Dawley rats and tested our hypothesis that OPN treatment would improve neurological outcomes, lesion and brain tissue characteristics, neuroinflammation, and vascular characteristics at 1 day post-injury. Intranasal OPN administered 1 hr after the TBI did not improve neurological score, lesion volumes, blood–brain barrier, or vascular characteristics. When assessing neuroinflammation, we did not observe any effect of OPN on the astrocyte reactivity but discovered an increased number of activated microglia within the ipsilateral hemisphere. Moreover, we found a correlation between edema and heme oxygenase-1 (HO-1) expression which was decreased in OPN-treated animals, suggesting an effect of OPN on the HO-1 response to injury. Thus, OPN may increase or accelerate the microglial response after TBI, and early response of HO-1 in modulating edema formation may limit the secondary consequences of TBI at later time points. Additional experiments and at longer time points are needed to determine if intranasal OPN could potentially be used as a treatment after TBI where it might be beneficial by activating protective signaling pathways.

Original languageEnglish
Pages (from-to)141-154
Number of pages14
JournalJournal of Neuroscience Research
Volume98
Issue number1
DOIs
StatePublished - Jan 1 2020

ASJC Scopus Subject Areas

  • Cellular and Molecular Neuroscience

Keywords

  • Heme oxygenase-1
  • T2 mapping
  • controlled cortical impact
  • edema
  • extracellular matrix protein
  • microglial activation
  • Microglia/drug effects
  • Neuroprotective Agents/administration & dosage
  • Rats
  • Male
  • Brain Edema/drug therapy
  • Brain Injuries, Traumatic/drug therapy
  • Rats, Sprague-Dawley
  • Signal Transduction/drug effects
  • Brain/drug effects
  • Animals
  • Blood-Brain Barrier/drug effects
  • Osteopontin/administration & dosage
  • Disease Models, Animal

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