ZFIN ID: ZDB-PUB-160923-12
A novel model of traumatic brain injury in adult zebrafish demonstrates response to injury and treatment comparable with mammalian models
McCutcheon, V., Park, E., Liu, E., Sobhe Bidari, P., Tavakkoli, J., Wen, X.Y., Baker, A.J.
Date: 2017
Source: Journal of neurotrauma   34(7): 1382-1393 (Journal)
Registered Authors: Wen, Xiao-Yan
Keywords: behavioral assessments, in vivo studies, models of injury, neural injury, traumatic brain injury
MeSH Terms:
  • Animals
  • Behavior, Animal/physiology*
  • Brain Injuries, Traumatic/drug therapy
  • Brain Injuries, Traumatic/physiopathology*
  • Brain Injuries, Traumatic/therapy*
  • Cysteine Proteinase Inhibitors/pharmacology*
  • Dipeptides/pharmacology
  • Disease Models, Animal*
  • Dizocilpine Maleate/pharmacology
  • Female
  • Hypothermia, Induced/methods*
  • Male
  • Neuroprotective Agents/pharmacology*
  • Ultrasonic Waves
  • Zebrafish*
PubMed: 27650063 Full text @ J. Neurotrauma
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ABSTRACT
Traumatic brain injury (TBI) is a leading cause of death and morbidity in industrialized countries with considerable associated healthcare costs. The cost and time associated with preclinical development of TBI therapeutics is lengthy and expensive with a poor track record of successful translation to the clinic. The zebrafish is an emerging model organism in research with unique technical and genomic strengths in the study of disease and development. Its high degree of genetic homology and cell signaling pathways relative to mammalian species and amenability to high and medium throughput assays has potential to accelerate the rate of therapeutic drug identification. Accordingly, we developed a novel closed-head model of TBI in adult zebrafish using a targeted pulsed high intensity focused ultrasound (pHIFU) to induce mechanical injury of the brain. Western blot results indicated altered microtubule and neurofilament expression as well as increased expression of cleaved caspase-3 and β-APP (P<0.05). We used automated behavioural tracking software to evaluate locomotor deficits 24 and 48 hours post-injury. Significant behavioural impairment included decreased swim distance and velocity (P<0.05), as well as heightened anxiety and altered group social dynamics. Responses to injury were pHIFU dose-dependent and modifiable with MK-801, MDL-28170 or temperature modulation. Together, results indicate that the zebrafish exhibits responses to injury and intervention similar to mammalian TBI pathophysiology and suggest the potential for use to rapidly evaluate therapeutic compounds with high efficiency.
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