“…Unlike many other constitutively expressed SUR1 regulated channels in various systemic tissues, SUR1-TRPM4 is unique in that it is not normally present in the CNS, but undergoes de novo upregulation after CNS injury [36]. Upregulation of SUR1 with or without TRPM4 (hereafter SUR1±TRPM4) has been demonstrated in multiple CNS cell types (neurons, astrocytes, endothelial cells, macrophages, microglia) and models of injury, including ischemic stroke [56][57][58][59], TBI [50,[60][61][62], spinal cord injury (SCI) [63,64], intracerebral hemorrhage (ICH) [65], subarachnoid hemorrhage (SAH) [66,67], CNS metastases [68], cardiac arrest [69,70], hepatic failure [71], and encephalomyelitis [72][73][74] ( Figure 1A). The increased expression in several cell-types of the neurovascular unit renders SUR1-TRPM4 a likely contributor across the spectrum of cerebral edema endotypes (reviewed elsewhere [14,15,75]), including cellular/cytotoxic edema, ionic edema, vasogenic edema, and eventually hemorrhagic transformation/progression with complete disintegration of the BBB and oncotic death of endothelial cells ( Figure 1C) [14,15,76].…”