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

Mol Neurobiol. 2018 Jan;55(1):187-200. doi: 10.1007/s12035-017-0732-y.


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.

Keywords: Alpha-linolenic acid; Anxiety disorders; Controlled cortical impact; Rat; Traumatic brain injury.

Publication types

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

MeSH terms

  • Animals
  • Anxiety / etiology
  • Anxiety / physiopathology
  • Anxiety / prevention & control*
  • Brain Injuries, Traumatic / complications
  • Brain Injuries, Traumatic / drug therapy*
  • Brain Injuries, Traumatic / physiopathology
  • Contusions / drug therapy*
  • Contusions / etiology
  • Contusions / physiopathology
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • alpha-Linolenic Acid / pharmacology
  • alpha-Linolenic Acid / therapeutic use*


  • alpha-Linolenic Acid