Alpha-linolenic acid given as enteral or parenteral nutritional intervention against sensorimotor and cognitive deficits in a mouse model of ischemic stroke

Neuropharmacology. 2016 Sep:108:60-72. doi: 10.1016/j.neuropharm.2016.04.040. Epub 2016 Apr 29.


Stroke is a leading cause of disability and death worldwide. Numerous therapeutics applied acutely after stroke have failed to improve long-term clinical outcomes. An emerging direction is nutritional intervention with omega-3 polyunsaturated fatty acids acting as disease-modifying factors and targeting post-stroke disabilities. Our previous studies demonstrated that the omega-3 precursor, alpha-linolenic acid (ALA) administrated by injections or dietary supplementation reduces stroke damage by direct neuroprotection, and triggering brain artery vasodilatation and neuroplasticity. Successful translation of putative therapies will depend on demonstration of robust efficacy on common deficits resulting from stroke like loss of motor control and memory/learning. This study evaluated the value of ALA as adjunctive therapy for stroke recovery by comparing whether oral or intravenous supplementation of ALA best support recovery from ischemia. Motor and cognitive deficits were assessed using rotarod, pole and Morris water maze tests. ALA supplementation in diet was better than intravenous treatment in improving motor coordination, but this improvement was not due to a neuroprotective effect since infarct size was not reduced. Both types of ALA supplementation improved spatial learning and memory after stroke. This cognitive improvement correlated with higher survival of hippocampal neurons. These results support clinical investigation establishing therapeutic plans using ALA supplementation.

Keywords: Alpha-linolenic acid; Disease modifiers; Docosahexaenoic acid (PubChem CID 445580); Eicosapentaenoic acid (PubChem CID 446284); Linolenate (PubChem CID 5280934); Linolenic acid; Neuroprotection; Nutraceutical; Nutrition; Polyunsaturated fatty acids; Stroke outcome and recovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / diet therapy*
  • Brain Ischemia / pathology
  • Cognitive Dysfunction / diet therapy*
  • Cognitive Dysfunction / pathology
  • Disease Models, Animal
  • Enteral Nutrition / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parenteral Nutrition / methods*
  • Psychomotor Performance / drug effects
  • Psychomotor Performance / physiology
  • Stroke / diet therapy*
  • Stroke / pathology
  • alpha-Linolenic Acid / administration & dosage*


  • alpha-Linolenic Acid