Neuroprotective effect of docosahexaenoic acid in rat traumatic brain injury model via regulation of TLR4/NF-Kappa B signaling pathway

Abstract

Objective: The experiments were conducted to prove that docosahexaenoic acid (DHA) alleviates traumatic brain injury (TBI) through regulating TLR4/NF-Kappa B signaling pathway.

Methods: Bioinformatic analysis was performed using published data from Gene Expression Omnibus (GEO) database to investigate differentially expressed genes and signaling pathways. Controlled cortical impact (CCI) injury rat model was built, and DHA (16 mg/kg in DMSO, once each day) was used to treat TBI rats. Neurological severity score (NSS) and beam walking test and rotarod test were used to confirm whether DHA is neuron-protective against TBI. The expression of TLR4, NF-Kappa B p65, (TNF)-α and IL-1β were examined by qRT-PCR and western blot. The impact of DHA on neurocyte apoptosis was validated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining. The influence of DHA on CD11b and GFAP expression in the hippocampus was determined through immunohistochemical analysis.

Results: TLR4/NF Kappa B pathway was suggested to be closely correlated with TBI by bioinformatic analysis. DHA could improve the neurological function and learning and memory ability of rats after TBI as well as promote neurocytes from apoptosis. TLR4 expression and the expression of inflammatory mediator NF-Kappa B were also repressed by DHA treatment.

Conclusions: DHA exerted a neuron-protective influence in a rat model of TBI via repressing TLR4/NF-Kappa B pathway.

Keywords: Docosahexaenoic acid; Rat model; TLR-4/NK-Kappa B pathway; Traumatic brain injury.