Minocycline is a highly lipophilic semi-synthetic derivative of tetracycline that
ONX-0914 is a capable of crossing the blood–brain barrier. Minocycline exerts very promising neuroprotective properties such as inhibition of microglial activation, glutamate toxicity, and caspase 1-dependent apoptosis [20], [21], [22] and [23]. A recent study has demonstrated that a significantly better outcome with minocycline treatment can be achieved compared with placebo on 152 patients with acute ischemic stroke [24]. In a murine model of middle cerebral artery occlusion (MCAO), minocycline prevents the activation of microglia expressing HMGB1 within the brain and both
brain and plasma HMGB1 levels [25]. We have demonstrated that edaravone, which has an antioxidant property, suppresses HMGB1 release from the activated neuronal cells in vitro and in vivo [18], suggesting that HMGB1 may be released from neuronal cells as well as microglia in acute ischemic stroke. PC12 cells are widely used in studies of in vitro neuronal injury [26] and [27]. Minocycline protects PC12 cells from ischemic-like injury by oxygen–glucose deprivation (OGD) [28], thus suggesting that minocycline may directly inhibit HMGB1 release. However, the inhibition mechanism of HMGB1 release by minocycline remains unclear.