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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

Abstract

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.

Keywords

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

Abbreviations

AD

Alzheimer’s disease

ALS

Amyotrophic lateral sclerosis

Apaf-1

Apoptotic protease-activating factor 1

ATP

Adenosine triphosphate

Amyloid beta protein

BAD

Bcl-2-associated death promoter

Bax

Bcl-2-associated protein X

Bcl-2

B cell lymphoma 2

BID

BH3 interacting domain death agonist

BiP

Chaperon-binding protein

bTBI

Blast-induced traumatic brain injury

CHOP

CCAAT enhancer-binding protein homologous protein

CREB

cAMP response element-binding protein

ER

Endoplasmic reticulum

ERK

Extracellular signal-regulated kinase

ERS

Endoplasmic reticulum stress

HD

Huntington’s disease

ICH

Intracerebral hemorrhage

JNK

c-Jun N-terminal kinase

MAPK

Mitogen-activated protein kinase

mEPSCs

Miniature excitatory postsynaptic currents

MI

Myocardial infarction

MR

Mineralocorticoid receptor

NSR

Nuclear steroid receptor

PARP

Poly(ADP-ribose) polymerase

PD

Parkinson’s disease

PERK

Protein kinase RNA-like endoplasmic reticulum kinase

PI3K

Phosphatidylinositide 3-kinase

PKC

Protein kinase C

PSD-95

Postsynaptic density protein 95

TBI

Traumatic brain injury

TNF

Tumor necrosis factor

TUDCA

Tauroursodeoxycholic acid

TUNEL

Terminal deoxynucleotidyl transferase dUTP nick end labeling

UDCA

Ursodeoxycholic acid

UPR

Unfolded protein response

Notes

Acknowledgments

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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