Effect of biglycan on neural apoptosis in mice with early brain injury after subarachnoid hemorrhage

Objective To investigate the effect of biglycan (BGN) on neural apoptosis in mice with early brain injury (EBI) after subarachnoid hemorrhage (SAH). Methods SAH models were induced by endovascular perforation in young male C57BL/6J mice. (1) Totally, 48 mice were randomly divided into sham-operated group, SAH 6 h group, SAH 12 h group, SAH 24 h group, SAH 48 h group, and SAH 72 h group (n=8); the BGN protein and mRNA expressions were detected by Western blotting and real-time quantitative PCR (qRT-PCR). (2) Totally, 16 mice were randomly divided into sham-operated group and SAH 48 h group (n=8); immunofluorescent double staining was conducted to explore the BGN expression in the neurons of brain tissues. (3) Totally, 24 mice were randomly divided into sham-operated group, sham+control lentivirus group, and sham+BGN lentivirus group (n=8); BGN lentiviral vector and control lentivirus were administered intracerebroventricularly 7 d before sham-operation; qRT-PCR was performed to explore the BGN mRNA expression. (4) Totally, 48 mice were randomly divided into sham-operated group, SAH+control lentivirus group, and SAH+BGN lentivirus group (n=16); BGN lentiviral vector and control lentivirus were administered intracerebroventricularly 7 d before SAH; neurological scores were detected by modified Garcia scale and beam balance tests; TUNEL was used to detect the neuronal apoptosis, and Western blotting was performed to explore the expressions of nuclear transcription factor kappa B (NF-κB) and phosphorylated-(p-) NF-κB. Results (1) Mice in the SAH 48 h group had the highest BGN protein and mRNA expressions, which showed statistical differences as compared with the sham-operated group (P<0.05). (2) A majority of BGN expressions were detected in the neurons 48 h after SAH. (3) The sham+BGN lentivirus group had statistically lower BGN mRNA expression than the sham+control lentivirus group (P<0.05). (4) As compared with those in the SAH+control lentivirus group, both scores of modified Garcia scale and beam balance tests were significantly higher in SAH+BGN lentivirus group (6.125±1.246 vs. 13.000±1.309; 1.125±1.126 vs. 2.875±0.835), and neural apoptosis ratio and ratio of p-NF-κB/NF-κB were significantly lower in the SAH+BGN lentivirus group (51.950%±11.166% vs. 31.938%±7.705%; 1.161±0.156 vs. 0.886±0.142, P<0.05). Conclusion Inhibition of BGN can effectively reduce neuronal apoptosis in mice with EBI after SAH, and attenuate neurological deficits. Key words: Subarachnoid hemorrhage; Early brain injury; Biglycan; Neuron; Apoptosis