Minocycline ameliorates cognitive impairment in rats with trigeminal neuralgia by regulating microglial polarization

Abstract

Trigeminal neuralgia (TN)-related cognitive impairment is a common cause of decreased quality of life in patients and is closely associated with neuroinflammation. Although minocycline has demonstrated anti-inflammatory, analgesic, and neuroprotective functions, its role in treating TN-related cognitive impairment remains unreported. In this study, we used an in vivo TN model and an in vitro model of primary microglial neuroinflammation to investigate the potential effects of minocycline on cognitive function and microglial polarization in TN rats. Our results suggested that minocycline treatment attenuated cognitive deficits by alleviating hippocampal neuronal damage and enhancing synaptic plasticity in TN rats. Furthermore, both in vitro and in vivo assays demonstrated that minocycline polarized activated microglia to the M2 phenotype, leading to the reduction of pro-inflammatory factors, including tumor necrosis factor-α and interleukin-1, and an increase in the anti-inflammatory factors, such as interleukin-4 and interleukin-10, thereby attenuating neuroinflammation. Moreover, it was found that the TLR4/MyD88/NF-κB pathway was involved in the shift of microglia from a pro-inflammatory (M1) to an anti-inflammatory (M2). In summary, minocycline likely mediated the process of microglia polarization partly via the TLR4/MyD88/NF-κB pathway, promoting neuronal survival and restoring synaptic plasticity, thereby improving TN-related cognitive impairment.