Appraisal of the Neuroprotective Effect of Dexmedetomidine: A Meta-Analysis.

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-1ß, 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-1ß (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.