Molecular Neurobiology

, Volume 55, Issue 1, pp 187–200 | Cite as

Alpha-Linolenic Acid Treatment Reduces the Contusion and Prevents the Development of Anxiety-Like Behavior Induced by a Mild Traumatic Brain Injury in Rats

  • Taiza H. Figueiredo
  • Carolina L. Harbert
  • Volodymyr Pidoplichko
  • Camila P. Almeida-Suhett
  • Hongna Pan
  • Katia Rossetti
  • Maria F. M. Braga
  • Ann M. Marini


Approximately, 1.7 million Americans suffer a TBI annually and TBI is a major cause of death and disability. The majority of the TBI cases are of the mild type and while most patients recover completely from mild TBI (mTBI) about 10% result in persistent symptoms and some result in lifelong disability. Anxiety disorders are the second most common diagnosis post-TBI. Of note, TBI-induced anxiety disorders are difficult to treat and remain a chronic condition suggesting that new therapies are needed. Previous work from our laboratory demonstrated that a mild TBI induced an anxiety-like phenotype, a key feature of the human condition, associated with loss of GABAergic interneurons and hyperexcitability in the basolateral amygdala (BLA) in rodents 7 and 30 days after a controlled cortical impact (CCI) injury. We now confirm that animals display significantly increased anxiety-like behavior 30 days after CCI. The anxiety-like behavior was associated with a significant loss of GABAergic interneurons and significant reductions in the frequency and amplitude of spontaneous and miniature GABAA-receptor-mediated inhibitory postsynaptic currents (IPSCs) in the BLA. Significantly, subchronic treatment with alpha-linolenic acid (ALA) after CCI prevents the development of anxiety-like behavior, the loss of GABAergic interneurons, hyperexcitability in the BLA and reduces the impact injury. Taken together, administration of ALA after CCI is a potent therapy against the neuropathology and pathophysiological effects of mTBI in the BLA.


Traumatic brain injury Anxiety disorders Controlled cortical impact Rat Alpha-linolenic acid 



Research was sponsored by the US Army Research Office and the Defense Advanced Research Projects Agency (DARPA) and was accomplished under Cooperative Agreement Number W911NF-14-2-0100.

Compliance with Ethical Standards


The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office, DARPA, or the US Government.


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Copyright information

© US Government (outside the USA) 2017

Authors and Affiliations

  • Taiza H. Figueiredo
    • 1
  • Carolina L. Harbert
    • 1
  • Volodymyr Pidoplichko
    • 1
  • Camila P. Almeida-Suhett
    • 1
  • Hongna Pan
    • 2
  • Katia Rossetti
    • 1
  • Maria F. M. Braga
    • 1
  • Ann M. Marini
    • 2
  1. 1.Department of Anatomy, Physiology and GeneticsUniformed Services University of the Health SciencesBethesdaUSA
  2. 2.Department of Neurology and Program in NeuroscienceUniformed Services University of the Health SciencesBethesdaUSA

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