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The protective effects of statins in traumatic brain injury

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Abstract

Traumatic brain injury (TBI), often referred to as the “silent epidemic”, is the most common cause of mortality and morbidity worldwide among all trauma-related injuries. It is associated with considerable personal, medical, and economic consequences. Although remarkable advances in therapeutic approaches have been made, current treatments and clinical management for TBI recovery still remain to be improved. One of the factors that may contribute to this gap is that existing therapies target only a single event or pathology. However, brain injury after TBI involves various pathological mechanisms, including inflammation, oxidative stress, blood-brain barrier (BBB) disruption, ionic disturbance, excitotoxicity, mitochondrial dysfunction, neuronal necrosis, and apoptosis. Statins have several beneficial pleiotropic effects (anti-excitotoxicity, anti-inflammatory, anti-oxidant, anti-thrombotic, immunomodulatory activity, endothelial and vasoactive properties) in addition to promoting angiogenesis, neurogenesis, and synaptogenesis in TBI. Supposedly, using agents such as statins that target numerous and diverse pathological mechanisms, may be more effective than a single-target approach in TBI management. The current review was undertaken to investigate and summarize the protective mechanisms of statins against TBI. The limitations of conducted studies and directions for future research on this potential therapeutic application of statins are also discussed.

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Data availability

No primary data was presented in this review.

Abbreviations

AD:

Alzheimer’s disease

AJs:

Adherens junctions

ATP:

Adenosine 5 triphosphate

BBB:

Blood-brain barrier

Ca²+:

Calcium

CDC:

Center for disease control and prevention

CNS:

Central nervous system

CRP:

C-reactive protein

DAMPs:

Damage-associated molecular patterns

DB RCT:

Double-blind randomized clinical trial

DCs:

Dendritic cells

DG:

Dentate gyrus

DRS:

Disability rating scale

eNOS:

Endothelial isoform of nitric oxide synthase

EPCs:

Endothelial progenitor cells

ESR:

Erythrocyte sedimentation rate

FDA:

Food and drug administration

GCS:

Glasgow coma scale

GOS:

Glasgow outcome scale

HMG CoA:

3-hydroxy-3-methylglutaryl coenzyme A

ICAM-1:

Intercellular adhesion molecule 1

ICP:

Intracranial pressure

ICU:

Intensive care unit

IL:

Interleukin

iNOS:

Inducible isoform of nitric oxide synthase

LDL:

Low-density lipoprotein

LTP:

Long-term potentiation

MRS:

Modified rankin scale

MSCs:

Mesenchymal stromal cells

NMDA:

N-methyl-D-aspartate

nNOS:

Neuronal isoform of nitric oxide synthase

NO:

Nitric oxide

NSC:

Neural stem cells

PMN:

Polymorphonuclear leukocytes

PRRs:

Pattern recognition receptors

ROS:

Reactive oxygen species

TBI:

Traumatic brain injury

TJs:

Tight junctions

TLR:

Toll-like receptors

TNF-α:

Ttumor necrosis factor-alpha

Tregs:

Regulatory T cells

VEGF:

Vascular endothelial growth factor

VEGFR-2:

VEGF receptor

vWF:

von Willebrand factor

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Authors and Affiliations

  1. Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Safoora Pordel

  2. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK

    Alice P. McCloskey

  3. Heart and Vascular Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

    Wael Almahmeed

  4. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

  5. Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Amirhossein Sahebkar

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  1. Safoora Pordel
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  2. Alice P. McCloskey
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  3. Wael Almahmeed
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  4. Amirhossein Sahebkar
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Conceptualization: AS, SP; Writing-original draft: SP; Writing-review & editing: APM, WA, AS.

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Correspondence to Amirhossein Sahebkar.

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We declare that some parts of Figs. 1 and 2 were drawn using pictures from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/). This Figure was modified with text, markings, and annotation using Microsoft Office PowerPoint (version 2010).

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Pordel, S., McCloskey, A.P., Almahmeed, W. et al. The protective effects of statins in traumatic brain injury. Pharmacol. Rep 76, 235–250 (2024). https://doi.org/10.1007/s43440-024-00582-9

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