Recombinant human brain-derived neurotrophic factor prevents neuronal apoptosis in a novel in vitro model of subarachnoid hemorrhage

Abstract

Mingchang Li,1 Yuefei Wang,1 Wei Wang,1 Changlin Zou,1 Xin Wang,2 Qianxue Chen1 1Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 2Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Abstract: Subarachnoid hemorrhage (SAH) is a hemorrhagic stroke with high mortality and morbidity. An animal model for SAH was established by directly injecting a hemolysate into the subarachnoid space of rats or mice. However, the in vitro applications of the hemolysate SAH model have not been reported, and the mechanisms remain unclear. In this study, we established an in vitro SAH model by treating cortical pyramidal neurons with hemolysate. Using this model, we assessed the effects of recombinant human brain-derived neurotrophic factor (rhBDNF) on hemolysate-induced cell death and related mechanisms. Cortical neurons were treated with 10 ng/mL or 100 ng/mL rhBDNF prior to application of hemolysate. Hemolysate treatment markedly increased cell loss, triggered apoptosis, and promoted the expression of caspase-8, caspase-9, and cleaved caspase-3. rhBDNF significantly inhibited hemolysate-induced cell loss, neuronal apoptosis, and expression of caspase-8, caspase-9, and cleaved caspase-3. Our data revealed a previously unrecognized protective activity of rhBDNF against hemolysate-induced cell death, potentially via regulation of caspase-9-, caspase-8-, and cleaved caspase-3-related apoptosis. This study implicates that hemolysate-induced cortical neuron death represents an important in vitro model of SAH. Keywords: recombinant human brain-derived neurotrophic factor, subarachnoid hemorrhage, neuroprotection, neuron, apoptosis

Keywords

• Recombinant human brain-derived neurotrophic factor
• subarachnoid hemorrhage
• neuroprotection
• neuron
• apoptosis