Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke.

Ischemic stroke, the second leading cause of death worldwide, leads to excessive glutamate release, over-activation of N-methyl-D-aspartate receptor (NMDAR), and massive influx of calcium (Ca2+), which may activate calpain and caspase-3, resulting in cellular damage and death. Memantine is an uncompetitive NMDAR antagonist with low-affinity/fast off-rate. We investigated the potential mechanisms through which memantine protects against ischemic stroke in vitro and in vivo. Middle cerebral artery occlusion-reperfusion (MCAO) was performed to establish an experimental model of ischemic stroke. The neuroprotective effects of memantine on ischemic rats were evaluated by neurological deficit scores and infarct volumes. The activities of calpain and caspase-3, and expression levels of microtubule-associated protein-2 (MAP2) and postsynaptic density-95 (PSD95) were determined by Western blotting. Additionally, Nissl staining and immunostaining were performed to examine brain damage, cell apoptosis, and neuronal loss induced by ischemia. Our results show that memantine could significantly prevent ischemic stroke-induced neurological deficits and brain infarct, and reduce ATP depletion-induced neuronal death. Moreover, memantine markedly suppressed the activation of the calpain-caspase-3 pathway and cell apoptosis, and consequently, attenuated brain damage and neuronal loss in MCAO rats. These results provide a molecular basis for the role of memantine in reducing neuronal apoptosis and preventing neuronal damage, suggesting that memantine may be a promising therapy for stroke patients.

Chen B ，Wang G ，Li W ，Liu W ，Lin R ，Tao J ，Jiang M ，Chen L ，Wang Y ... -  《-》

The mechanism of taurine protection against endoplasmic reticulum stress in an animal stroke model of cerebral artery occlusion and stroke-related conditions in primary neuronal cell culture.

Gharibani PM ，Modi J ，Pan C ，Menzie J ，Ma Z ，Chen PC ，Tao R ，Prentice H ，Wu JY ... -  《Advances in Experimental Medicine and Biology》

Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia.

Sun M ，Xu C 《-》

The erythropoietin-derived peptide MK-X and erythropoietin have neuroprotective effects against ischemic brain damage.

Yoo SJ ，Cho B ，Lee D ，Son G ，Lee YB ，Soo Han H ，Kim E ，Moon C ，Moon C ... -  《-》

Neuroprotective effects of a novel single compound 1-methoxyoctadecan-1-ol isolated from Uncaria sinensis in primary cortical neurons and a photothrombotic ischemia model.

Jang JY ，Choi YW ，Kim HN ，Kim YR ，Hong JW ，Bae DW ，Park SJ ，Shin HK ，Choi BT ... -  《PLoS One》