Neuropathology and applied neurobiology
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Neuropathol. Appl. Neurobiol. · Apr 2014
Possible involvement of cathepsin B/D and caspase-3 in deferoxamine-related neuroprotection of early brain injury after subarachnoid haemorrhage in rats.
Deferoxamine (DFX) has recently been shown to have a neuroprotective effect in animal models of subarachnoid haemorrhage (SAH). However, the precise mechanisms underlying these effects remain unclear. Our previous studies found that iron overload in lysosomes leads to lysosomal membrane damage and rupture, and then induces cell apoptosis in the oxidative stress conditions in vitro. We therefore analysed the time-course of the two of major lysosomal cathepsins (cathepsin B/D) and caspase-3 expression in brain and evaluated how DFX might affect these proteins and the parameters concerning early brain injury (EBI) after SAH. ⋯ These results suggest that the lysosomal membrane may be damaged after SAH, which leads to the release of proteases (cathepsin B/D) and activates the apoptotic pathway. Iron overload may be one key mechanism underlying SAH-induced oxidative stress and DFX may protect the lysosomal membrane, inhibit the release of cathepsin B/D, and ameliorate EBI by suppressing iron overload in the acute phase of SAH.