Clinical as well as basic research in the past decades has revealed the crucial importance of cerebral endothelial cell (CEC) dysfunction contributing to secondary injury following primary brain ischemic insults. Multiple postischemic events including inflammation, blood-brain barrier (BBB) breakdown, vasogenic brain edema, and hemorrhagic transformation are known to worsen the clinical outcomes of stroke patients, all of which are closely associated with CEC dysfunction. Oxidative stress with excessive production of reactive oxygen species (ROS) or free radicals has been considered to be one of the major factors in causing ischemic brain damages. In this chapter, we first discuss the sources of ROS and its contribution to vascular injury as well as recent progresses using antioxidant enzymes, most notably SOD and catalase, to attenuate ischemic injury. Cerebral ischemia results in damages of the brain vasculature with breaching of the normally impermeable BBB, thereby leading to vasogenic brain edema after stroke. We then review the potential importance of several proteins known to be involved in BBB breakdown after stroke, including matrix metalloproteinases (MMPs), endothelin, vascular endothelial growth factor (VEGF), angiopoietin, and nitric oxide synthase (NOS). Postischemic inflammatory reaction is another detrimental event causing secondary vascular injury, and thus exacerbating the primary ischemic damage. CEC dysfunction may promote adherence and infiltration of inflammatory cells, including neutrophils, macrophages, lymphocytes, and platelets. Therefore, cell and protein mediators contributing to postischemic inflammation are discussed. We also discuss several redox-sensitive transcription factors including hypoxia-inducible factor-1 (HIF-1), nuclear factor kappa-B (NF-κB), and activator protein-1 (AP-1) that are activated after cerebral ischemia to alter CEC viability and postischemic angiogenesis. Finally, potential therapeutic strategies such as statins, ischemic preconditioning (IPC) or LPS preconditioning, and prostaglandins that have been shown to exert protective effects in the settings of cerebral ischemia via mechanisms involving endothelial functions are emphasized.
|Title of host publication||Handbook of Neurochemistry and Molecular Neurobiology: Acute Ischemic Injury and Repair in the Nervous System|
|Number of pages||19|
|Publication status||Published - 2007|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)