The maxi-K channel opener EMS-204352 attenuates regional cerebral edema and neurologic motor impairment after experimental brain injury

Large-conductance, calcium-activated potassium (maxi-K) channels regulate n eurotransmitter release and neuronal excitability, and openers of these cha nnels have been shown to be neuroprotective in models of cerebral ischemia. The authors evaluated the effects of postinjury systemic administration of the maxi-K channel opener, BMS-204352, on behavioral and histologic outcom e after lateral fluid percussion (PP) traumatic brain injury (TBI) in the r at. Anesthetized Sprague Dawley rats (n = 142) were subjected to moderate F P brain injury (n = 88) or surgery without injury(n = 54) and were randomiz ed to receive a bolus of 0.1 mg/kg BMS-204352 (n = 26, injured; n = 18, sha m), 0.03 mg/kg BMS-201352 (n = 25, injured; n = 18, sham), or 2% dimethyl s ulfoxide (DMSO) in polyethylene glycol (vehicle, n = 27, injured; n = 18. s ham) at IO minutes postinjury. One group of rats was tested for memory rete ntion (Morris water maze) at 42 hours postinjury, then killed for evaluatio n of regional cerebral edema. A second group of injured/sham rats was asses sed for neurologic motor function from 48 hours to 2 weeks postinjury and c ortical lesion area. Administration of 0.1 mg/kg BMS-204352 improved neurol ogic motor function at 1 and 2 weeks postinjury (P < 0.05) and reduced the extent of cerebral edema in the ipsilateral hippocampus, thalamus, and adja cent cortex (P < 0.05). Administration of 0.03 mg/kg EMS-204352 significant ly reduced cerebral edema in the ipsilateral thalamus (P < 0.05). No effect s on cognitive function or cortical tissue loss were observed with either d ose. These results suggest that the novel maxi-a channel opener BMS-204352 may be selectively beneficial in the treatment of experimental TBI.