Journal of neurochemistry
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Journal of neurochemistry · Aug 2020
Angiopoietin-1/Tie-2 signal after focal traumatic brain injury is potentiated by BQ788, an ETB receptor antagonist, in the mouse cerebrum: Involvement in recovery of blood-brain barrier function.
Angiopoietin-1, an angiogenic factor, stabilizes brain microvessels through Tie-2 receptor tyrosine kinase. In traumatic brain injury, blood-brain barrier (BBB) disruption is an aggravating factor that induces brain edema and neuroinflammation. We previously showed that BQ788, an endothelin ETB receptor antagonist, promoted recovery of BBB function after lateral fluid percussion injury (FPI) in mice. ⋯ Five days after FPI, increased extravasation of Evans blue dye accompanied by reduction in claudin-5, occludin, and zonula occludens-1 proteins were observed in mouse cerebrum while these effects of FPI were reduced by BQ788 and exogenous angiopoietin-1 (1 μg/day, i.c.v.). The effects of BQ788 were inhibited by co-administration of a Tie-2 kinase inhibitor (40 nmol/day, i.c.v.). These results suggest that BQ788 administration after traumatic brain injury promotes recovery of BBB function through activation of the angiopoietin-1/Tie-2 signal.
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Journal of neurochemistry · Aug 2020
Involvement of homodomain interacting protein kinase 2-c-Jun N-terminal kinase/c-Jun cascade in the long-term synaptic toxicity and cognition impairment induced by neonatal Sevoflurane exposure.
Sevoflurane is one of the most widely used anesthetics with recent concerns rising about its pediatric application. The synaptic toxicity and mechanisms underlying its long-term cognition impairment remain unclear. In this study, we investigated the expression and roles of homeodomain interacting protein kinase 2 (HIPK2), a stress activating kinase involved in neuronal survival and synaptic plasticity, and its downstream c-Jun N-terminal kinase (JNK)/c-Jun signaling in the long-term toxicity of neonatal Sevoflurane exposure. ⋯ JNK antagonist SP600125 partially restored synapse development and cognitive function without affecting the expression of HIPK2. These data, in together, revealed a novel role of HIPK2-JNK/c-Jun signaling in the long-term synaptic toxicity and cognition impairment of neonatal Sevoflurane exposure, indicating HIPK2-JNK/c-Jun cascade as a potential target for reducing the synaptic toxicity of Sevoflurane. Cover Image for this issue: doi: 10.1111/jnc.14757.