Abstract:
:Integrin β8 is a key regulator of vascular homeostasis in brain development and in vitro studies show that β8 protects against oxygen-glucose deprivation-induced neuronal apoptosis. However, the role β8 plays in vivo in neonatal rats with hypoxic-ischemic (HI) brain injury is not known. Here, we report the function of β8 and signaling pathways involved in neuroprotection after neonatal brain HI. Neonatal HI model was performed in postnatal day 10 rats by ligating the right common carotid artery, followed by hypoxia exposure. Expressions of β8 were determined by immunohistochemistry, immunofluorescence, reverse transcription polymerase chain reaction, and western blot. We used lentiviral vector-mediated β8 RNAi to inhibit integrin β8, GM6001 to inhibit matrix metalloprotease, and the TGF-β1 neutralizing antibody 1d11 to inhibit TGF-β1. The expression of vascular endothelial growth factor, ERK1/2 and p-ERK1/2, Bcl-2, Bax, and cleaved caspase 3 (CC3) were detected by western blot. Cellular apoptosis was detected with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling. β8 was mainly localized to astrocytes and upregulated immediately upon HI. When β8/TGF-β1 was inhibited, phosphorylated ERK1/2 was downregulated, followed by the downregulation of vascular endothelial growth factor (VEGF) and Bcl-2/Bax, and upregulation of CC3 and cellular apoptosis. The activation of TGF-β1 and ERK1/2 are involved in β8-induced VEGF expression and neuronal survival. The anti-apoptotic effect of β8 may be attributed to regulation of Bcl-2/Bax balance and caspase 3. β8 might be a potential target for therapeutic intervention in neonates with HI brain injury.
journal_name
Neurotox Resjournal_title
Neurotoxicity researchauthors
Zhang L,Qu Y,Tang B,Zhao F,Xiong T,Ferriero D,Mu Ddoi
10.1007/s12640-012-9312-0subject
Has Abstractpub_date
2012-11-01 00:00:00pages
280-91issue
4eissn
1029-8428issn
1476-3524journal_volume
22pub_type
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