Gambogic amide, a selective TrkA agonist, does not improve outcomes from traumatic brain injury in mice

Maddison R. Johnstone, Mujun Sun, Caroline J. Taylor, Rhys D. Brady, Brian L. Grills, Jarrod E. Church, Sandy R. Shultz, Stuart J. McDonald

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objectives: There is evidence that treatment with nerve growth factor (NGF) may reduce neuroinflammation and apoptosis after a traumatic brain injury (TBI). NGF is thought to exert its effects via binding to either TrkA or p75 neurotrophin receptors. This study aimed to investigate the effects of a selective TrkA agonist, gambogic amide (GA), on TBI pathology and outcomes in mice following lateral fluid percussion injury. Methods: Male C57BL/6 mice were given either a TBI or sham injury, and then received subcutaneous injections of either 2 mg/kg of GA or vehicle at 1, 24, and 48 h post-injury. Following behavioural studies, mice were euthanized at 72 h post-injury for analysis of neuroinflammatory, apoptotic, and neurite outgrowth markers. Results: Behavioural testing revealed that GA did not mitigate motor deficits after TBI. TBI caused an increase in cortical and hippocampal expression of several markers of neuroinflammation and apoptosis compared to sham groups. GA treatment did not attenuate these increases in expression, possibly contributed to by our finding of TrkA receptor down-regulation post-TBI. Conclusions: These findings suggest that GA treatment may not be suitable for attenuating TBI pathology and improving outcomes.

Original languageEnglish
Pages (from-to)257-268
Number of pages12
JournalBrain Injury
Volume32
Issue number2
DOIs
Publication statusPublished - 28 Jan 2018

Keywords

  • apoptosis
  • behaviour
  • Nerve growth factor
  • neurite growth
  • neuroinflammation
  • synaptogenesis

Cite this

Johnstone, Maddison R. ; Sun, Mujun ; Taylor, Caroline J. ; Brady, Rhys D. ; Grills, Brian L. ; Church, Jarrod E. ; Shultz, Sandy R. ; McDonald, Stuart J. / Gambogic amide, a selective TrkA agonist, does not improve outcomes from traumatic brain injury in mice. In: Brain Injury. 2018 ; Vol. 32, No. 2. pp. 257-268.
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Gambogic amide, a selective TrkA agonist, does not improve outcomes from traumatic brain injury in mice. / Johnstone, Maddison R.; Sun, Mujun; Taylor, Caroline J.; Brady, Rhys D.; Grills, Brian L.; Church, Jarrod E.; Shultz, Sandy R.; McDonald, Stuart J.

In: Brain Injury, Vol. 32, No. 2, 28.01.2018, p. 257-268.

Research output: Contribution to journalArticleResearchpeer-review

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