Highlight► A unique catalogue of phenotype markers and neuronotoxic effects of polarised primary microglia, as a comparative tool to screen neurotherapies.

Dexmedetomidine is a potent alpha-2-adrenergic agonist, more selective than clonidine, with widespread actions on the mammalian brain that include sedation, anaesthetic-sparing, analgesia and sympatholytic properties. A large body of recent work supports its favourable profile in improving outcome and long-term brain function in the critically ill. The source of these benefits may lie in the neuroprotective properties that are seen in experimental models and in the clinical setting, in which it can attenuate delirium, preserve sleep architecture, preserve ventilatory drive and decrease sympathetic tone and inflammatory response. Dexmedetomidine may also be a valuable adjuvant when regional anaesthesia is used. Future research should aim at establishing the risk/benefit ratio when used at the bedside.

Our findings link inflammation and excitotoxicity in a potential vicious circle and indicate that an activation of the microglial NMDARs plays a pivotal role in neuronal cell death in the perinatal and adult brain.