Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage

AbstractSubarachnoid haemorrhage (SAH) is a type of hemorrhagic stroke that is associated with high morbidity and mortality. New effective treatments are needed to improve outcomes. The pathophysiology of SAH is complex and includes early brain injury and delayed cerebral ischemia, both of which are characterized by blood–brain barrier (BBB) impairment. We isolated brain endothelial cells (BECs) from mice subjected to SAH by injection of blood into the prechiasmatic cistern. We used gene expression profiling to identify 707 unique genes (2.8% of transcripts, 403 upregulated, 304 downregulated, 24,865 interrogated probe sets) that were significantly differentially expressed in mouse BECs after SAH. The pathway involving prostaglandin synthesis and regulation was significantly upregulated after SAH, including increased expression of the Ptgs2 gene and its corresponding COX-2 protein. Celecoxib, a selective COX-2 inhibitor, limited upregulation of Ptgs2 in BECs. In this study, we have defined the gene expression profiling of BECs after experimental SAH and provide further insight into BBB pathophysiology, which may be relevant to other neurological diseases such as traumatic brain injury, brain tumours, ischaemic stroke, multiple sclerosis, and neurodegenerative disorders.

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Gene Expression Profiling for Discovery of Novel Targets in Human Traumatic Brain Injury

Biological Research For Nursing ◽

10.1177/1099800410385671 ◽

2010 ◽

Vol 13 (2) ◽

pp. 140-153 ◽

Cited By ~ 10

Author(s):

Taura L. Barr ◽

Sheila Alexander ◽

Yvette Conley

Keyword(s):

Gene Expression ◽

Traumatic Brain Injury ◽

Clinical Trials ◽

Brain Injury ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Treatment Strategies ◽

Biological Pathways ◽

Human Response ◽

Novel Targets

Several clinical trials have failed to demonstrate a significant effect on outcome following human traumatic brain injury (TBI) despite promising results obtained in preclinical animal studies. These failures may be due in part to a misinterpretation of the findings obtained in preclinical animal models of TBI, a misunderstanding of the complexity of the human response to TBI, limited knowledge about the biological pathways that interact to contribute to good and bad outcomes after brain injury, and the effects of genomic variability and environment on individual recovery. Recent publications suggest that data obtained from gene expression profiling studies of complex neurological diseases such as stroke, multiple sclerosis (MS), Alzheimer’s and Parkinson’s may contribute to a more informed understanding of what affects outcome following TBI. These data may help to bridge the gap between successful preclinical studies and negative clinical trials in humans to reveal novel targets for therapy. Gene expression profiling has the capability to identify biomarkers associated with response to TBI, elucidate complex genetic interactions that may play a role in outcome following TBI, and reveal biological pathways related to brain health. This review highlights the current state of the literature on gene expression profiling for neurological disease and discusses its ability to aid in unraveling the variable human response to TBI and the potential for it to offer treatment strategies in an area where we currently have limited therapeutic options primarily based on supportive care.

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