Abstract
Dexmedetomidine is an adrenergic receptor agonist that has been regarded as neuroprotective in several studies without an objective measure to it. Thus, the aim of this meta-analysis was to analyze and quantify the current evidence for the neuroprotective effects of dexmedetomidine in animals. The search was performed by querying the National Library of Medicine. Studies were included based on their language, significancy of their results, and complete availability of data on animal characteristics and interventions. Risk of bias was assessed using SYRCLE’s risk of bias tool and certainty was assessed using the ARRIVE Guidelines 2.0. Synthesis was performed by calculating pooled standardized mean difference and presented in forest plots and tables. The number of eligible records included per outcome is the following: 22 for IL-1β, 13 for IL-6, 19 for apoptosis, 7 for oxidative stress, 7 for Escape Latency, and 4 for Platform Crossings. At the cellular level, dexmedetomidine was found protective against production of IL-1β (standardized mean difference (SMD) = − 4.3 [− 4.8; − 3.7]) and IL-6 (SMD = − 5.6 [− 6.7; − 4.6]), apoptosis (measured through TUNEL, SMD = − 6.0 [− 6.8; − 4.6]), and oxidative stress (measured as MDA production, SMD = − 2.0 [− 2.4; − 1.4]) exclusively in the central nervous system. At the organism level, dexmedetomidine improved behavioral outcomes measuring escape latency (SMD = − 2.4 [− 3.3; − 1.6]) and number of platform crossings (SMD = 9.1 [− 6.8; − 11.5]). No eligible study had high risk of bias and certainty was satisfactory for reproducibility in all cases. This meta-analysis highlights the complexity of adrenergic stimulation and sheds light into the mechanisms potentiated by dexmedetomidine, which could be exploited for improving current neuroprotective formulations.
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Abbreviations
- AR:
-
Adrenergic receptor
- ARRIVE:
-
Animal Research: Reporting of In Vivo Experiments
- cAMP:
-
Cyclic adenosine monophosphate
- CI:
-
Confidence interval
- CNS:
-
Central nervous system
- DAG:
-
Diacylglycerol
- DRG:
-
Dorsal root ganglion
- GIRKs:
-
G protein-coupled inwardly-rectifying K+ channels
- MDA:
-
Malondialdehyde
- NMDAR:
-
NMDA-type glutamatergic receptors
- OXPHOS:
-
Oxidative phosphorylation
- OSP:
-
Outlier, significance, and precision
- PKA:
-
Protein kinase A
- PLC:
-
Phospholipase C
- PIP2:
-
Phosphatidylinositol 4,5-bisphosphate
- PKC:
-
Protein kinase C
- PRISMA:
-
Preferred Reporting Items for Systematic reviews and Meta-Analyses
- ROS:
-
Reactive oxygen species
- SMD:
-
Standardized mean difference
- SYRCLE:
-
SYstematic Review Centre for Laboratory animal Experimentation
- TUNEL:
-
Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling
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Statements and Declarations
Funding
This work was supported by Fondo Nacional de Desarrollo Científico y Tecnológico FONDECYT [Grant numbers 3220565 (SG), 1201039 (FS), 11170840 (CE), 1191300 (CR)]; Millennium Science Initiative Program—ICN09_016/ICN 2021_045: Millennium Institute on Immunology and Immunotherapy (ICN09_016/ICN 2021_045; former P09/016-F) (FS, CR); The Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD) is supported by the Iniciativa Científica Milenio ANID, Chile (FS); Ministry of Education, Science and Technological Development of the Republic of Serbia (grant number 451-03-9/2021-14/200015) (JFS).
Disclosure of Interests
All authors declare they have no conflict of interest.
Ethical Approval
This article does not contain any studies with human participants or animals performed by any of the authors.
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SG, CA, YP, and DA extracted and analyzed the data. SG, CE, CR, JFS, and FS, collectively contributed to manuscript drafting. All authors read and approved the final manuscript.
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Gatica, S. et al. (2023). Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis. In: Simon, F., Bernabeu, C. (eds) Advances in Molecular Pathology. Advances in Experimental Medicine and Biology, vol 1408. Springer, Cham. https://doi.org/10.1007/978-3-031-26163-3_9
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