X-linked inhibitor of apoptosis inhibits apoptosis and preserves the blood-brain barrier after experimental subarachnoid hemorrhage.
Early brain injury following subarachnoid hemorrhage (SAH) strongly determines the prognosis of patients suffering from an aneurysm rupture, and apoptosis is associated with early brain injury after SAH. This study was designed to explore the role of X-linked inhibitor of apoptosis (XIAP) in early brain injury following SAH. The expression of XIAP was detected using western blotting and real-time RT-PCR in an autologous blood injection model of SAH. We also studied the role of XIAP in early brain injury and detected apoptosis-related proteins. The results showed that XIAP was significantly up-regulated in the cortex and hippocampus and that XIAP was mainly expressed in neuronal cells following SAH. The inhibition of endogenous XIAP aggravated blood-brain barrier disruption, neurological deficits and brain edema. Recombinant XIAP preserved the blood-brain barrier, improved the neurological scores and ameliorated brain edema. Recombinant XIAP treatment also decreased the expression of cleaved caspase-3, caspase-8 and caspase-9, whereas there was no effect on the expression of p53, apoptosis-inducing factor or cytochrome c. These results show that XIAP acts as an endogenous neuroprotective and anti-apoptotic agent following SAH. The effects of XIAP on early brain injury was associated with the inhibition of the caspase-dependent apoptosis pathway.
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Cheng
C
Gao
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Hongwei
H
Yu
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Cong
C
Yan
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Wenyang
W
Zhao
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Yao
Y
Liu
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Dongdong
D
Zhang
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Jingwei
J
Li
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Nan
N
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D008297:Male; D051381:Rats; D011994:Recombinant Proteins; D013345:Subarachnoid Hemorrhage / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D011994:Recombinant Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein