
Dezhi Mu MD PhD
Assistant
Research Neurobiologist
My research is focusing on the neuroprotective mechanisms in
neonatal ischemic brain injury. In vivo and in vitro experiments were performed
to prove our hypothesis that hypoxia-inducible factor 1 a (HIF1a) induction after
moderate focal ischemia leads to up-regulation of survival genes resulting in
neuroprotection in the developing nervous system.
To test this hypothesis, we first determined the effect of different degrees of
ischemia on the expression of HIF1a using a neonatal stroke model by transiently
occluding middle cerebral artery (MCA-O) followed by reperfusion in postnatal
day 10 (P10) rats. We found that HIF-1a expression is much stronger in moderate
ischemic (1.5 h MCA-O) rats than in severe ischemic (3 h MCA-O) rats.
We next investigated whether downstream protective genes of HIF1a such as vascular
endothelial growth factor (VEGF) and erythropoietin (Epo) etc. are upregulated.
HIF1a, VEGF and Epo mRNA and protein expressions were measured. The relationship
between HIF1a, VEGF and Epo expression and the histopathological outcome were
compared. We found the upregulation of HIF1a, VEGF and Epo is neuroprotective
in P10 rats.
Now, we are studying HIF1a signaling pathways in the P10 stroke model. We will
investigate the regulation and compare the neuroprotective roles of HIF1a and
its target genes in HIF1a knockout and wild mice using MCA-O stroke model. Meanwhile,
we will study the roles and signaling pathways of integrin avb8 and HIF1a target
gene VEGF in the P10 stroke model.
contact: dzmu@itsa.ucsf.edu
