Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke.

Abstract

Glial activation is involved in neuroinflammation and blood-brain barrier (BBB) damage, which plays a key role in ischemic stroke-induced neuronal damage; therefore, regulating glial activation is an important way to inhibit ischemic brain injury. Effects of laquinimod (LAQ) include inhibiting axonal damage and neuroinflammation in multiple neuronal injury diseases. However, whether laquinimod can exert neuroprotective effects after ischemic stroke remains unknown. In this study, we investigated the effect of LAQ on glial activation, BBB damage, and neuronal damage in an ischemic stroke model. Adult ICR mice were used to create a photothrombotic stroke (PT) model. LAQ was administered orally at 30 min after ischemic injury. Neurobehavioral tests, Evans Blue, immunofluorescence, TUNEL, Nissl staining, and western blot were performed to evaluate the neurofunctional outcome. Quantification of immunofluorescence was evaluated by unbiased stereology. LAQ post-treatment significantly reduced infarction and improved forepaw function at 5 days after PT. Interestingly, LAQ treatment significantly promoted anti-inflammatory microglial activation. Moreover, LAQ treatment reduced astrocyte activation, glial scar formation, and BBB breakdown in ischemic brains. Therefore, this study demonstrated that LAQ post-treatment restricted microglial polarization, astrogliosis, and glial scar and improved BBB damage and behavioral function. LAQ may serve as a novel target to develop new therapeutic agents for ischemic stroke.