Fluoxetine has neuroprotective effects after cardiac arrest and cardiopulmonary resuscitation in mouse

Aims: Fluoxetine, a selective serotonin reuptake inhibitor, is protective in a rat focal ischaemia model via anti-inflammatory mechanisms. Cardiac arrest and cardiopulmonary resuscitation (CA/CPR) were performed in mice to test the hypothesis that fluoxetine protects the brain following global cerebral ischaemia, even when administered after an insult. Methods: Global cerebral ischaemia was induced with 8 min CA/CPR in C57BL/6 male mice. Thirty minutes after recovery of spontaneous circulation, the mice were randomly assigned into 3 groups and administered fluoxetine; fluoxetine (5 mg/kg: n = 15, 10 mg/kg: n = 15) or vehicle (NaCl: n = 15). Three days after CA/CPR, sensorimotor evaluations were conducted and brains were removed for histological evaluation of the hippocampus and caudate putamen. Results: Analysis of histological damage 72 h after resuscitation revealed that low dose fluoxetine (5 mg/kg) did not protect, while high dose (10 mg/kg) fluoxetine protected neurons in the caudate putamen. In contrast, there were no protective effects in the hippocampus at either dose. In agreement with histological observations of neuronal damage in the caudate putamen, high dose fluoxetine decreased sensorimotor deficits following CA/CPR compared to vehicle-treated animals. Conclusions: Our data showed that 10 mg/kg fluoxetine administered following global cerebral ischaemia decreases neuronal damage. Although long-term neuroprotection needs further study, the results of our study suggest that fluoxetine may have therapeutic potential when administered after global cerebral ischaemia, cardiac arrest and cardiopulmonary resuscitation. (c) 2011 Elsevier Ireland Ltd. All rights reserved.