Content-Length: 62691 | pFad | http://www.ncbi.nlm.nih.gov/pubmed/30006635/

000 Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model

Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model

Sci Rep. 2018 Jul 13;8(1):10622. doi: 10.1038/s41598-018-28848-2.

Abstract

Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anxiety / drug therapy*
  • Anxiety / etiology
  • Anxiety / psychology
  • Behavior, Animal / drug effects
  • Blast Injuries / drug therapy
  • Blast Injuries / etiology
  • Blast Injuries / mortality
  • Blast Injuries / psychology
  • Brain Injuries / drug therapy
  • Brain Injuries / etiology
  • Brain Injuries / mortality
  • Brain Injuries / psychology
  • Dexamethasone / administration & dosage*
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Explosions
  • Hemostatics / administration & dosage*
  • Humans
  • Injections, Intravenous
  • Male
  • Multiple Trauma / drug therapy*
  • Multiple Trauma / etiology
  • Multiple Trauma / mortality
  • Multiple Trauma / psychology
  • Nanoparticles / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Treatment Outcome
  • Warfare

Substances

  • Drug Carriers
  • Hemostatics
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Dexamethasone








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