Neurocritical Care

, Volume 25, Issue 1, pp 153–166 | Cite as

Application of Tauroursodeoxycholic Acid for Treatment of Neurological and Non-neurological Diseases: Is There a Potential for Treating Traumatic Brain Injury?

  • Kyle R. Gronbeck
  • Cecilia M. P. Rodrigues
  • Javad Mahmoudi
  • Eric M. Bershad
  • Geoffrey Ling
  • Salam P. Bachour
  • Afshin A. Divani
Review Article


The objective of this review was to evaluate the potential of tauroursodeoxycholic acid (TUDCA) for neuroprotection in traumatic brain injury (TBI) patients in the neurocritical care setting. Specifically, we surveyed preclinical studies describing the neuroprotective and systemic effects of TUDCA, and the potential therapeutic application of TUDCA. Preclinical studies have provided promising data supporting its use in neurological disease characterized by apoptosis-induced neuronal loss. TUDCA inhibits multiple proteins involved in apoptosis and upregulates cell survival pathways. In addition, TUDCA exhibits anti-inflammatory effects in models of neuroinflammation and attenuates neuronal loss in chronic neurodegenerative diseases. This may be applicable to TBI, which also triggers inflammatory and apoptotic processes. Additionally, preliminary data support the use of pharmacological therapies that reduce apoptosis and inflammation associated with TBI. The anti-apoptotic and anti-inflammatory mechanisms of TUDCA could prove promising in the treatment of TBI. Currently, there are no published data supporting improvement in clinical outcomes of TBI by treatment with TUDCA, but future studies should be considered.


Traumatic brain injury Tauroursodeoxycholic acid Apoptosis Neuroprotection Intracranial pressure Edema Neuroinflammation Blast injury Stroke Intracerebral hemorrhage 



Alzheimer’s disease


Amyotrophic lateral sclerosis


Apoptotic protease-activating factor 1


Adenosine triphosphate

Amyloid beta protein


Bcl-2-associated death promoter


Bcl-2-associated protein X


B cell lymphoma 2


BH3 interacting domain death agonist


Chaperon-binding protein


Blast-induced traumatic brain injury


CCAAT enhancer-binding protein homologous protein


cAMP response element-binding protein


Endoplasmic reticulum


Extracellular signal-regulated kinase


Endoplasmic reticulum stress


Huntington’s disease


Intracerebral hemorrhage


c-Jun N-terminal kinase


Mitogen-activated protein kinase


Miniature excitatory postsynaptic currents


Myocardial infarction


Mineralocorticoid receptor


Nuclear steroid receptor


Poly(ADP-ribose) polymerase


Parkinson’s disease


Protein kinase RNA-like endoplasmic reticulum kinase


Phosphatidylinositide 3-kinase


Protein kinase C


Postsynaptic density protein 95


Traumatic brain injury


Tumor necrosis factor


Tauroursodeoxycholic acid


Terminal deoxynucleotidyl transferase dUTP nick end labeling


Ursodeoxycholic acid


Unfolded protein response



Kyle R. Gronbeck was supported by the University of Minnesota Medical Student Summer Research Grant and the 2015 Medical Student Summer Research Scholarship through the American Academy of Neurology (AAN). Dr. Divani has received research support from Lake Region Medical, Chaska, Minnesota, USA.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Kyle R. Gronbeck
    • 1
    • 2
  • Cecilia M. P. Rodrigues
    • 3
  • Javad Mahmoudi
    • 4
  • Eric M. Bershad
    • 5
  • Geoffrey Ling
    • 6
  • Salam P. Bachour
    • 1
  • Afshin A. Divani
    • 1
    • 7
    • 8
  1. 1.Department of NeurologyUniversity of MinnesotaMinneapolisUSA
  2. 2.Medical SchoolUniversity of MinnesotaMinneapolisUSA
  3. 3.Faculty of Pharmacy, Research Institute for Medicines (iMed.ULisboa)University of LisbonLisbonPortugal
  4. 4.Neurosciences Research CenterTabriz University of Medical SciencesTabrizIran
  5. 5.Department of NeurologyBaylor College of MedicineHoustonUSA
  6. 6.Department of NeurologyUniformed Services University of the Health SciencesBethesdaUSA
  7. 7.Department of Neurological SurgeryUniversity of MinnesotaMinneapolisUSA
  8. 8.Department of Biomedical EngineeringUniversity of MinnesotaMinneapolisUSA

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