ABSTRACT
BACKGROUND: Dysfunction of endothelial cells (ECs) constitutes a critical factor in the formation of intracranial aneurysms (IAs). However, little is known about the response of ECs to hemodynamic insults and its contribution to IA formation. METHODS: IAs models were constructed in both adult female New Zealand white rabbits and male Sprague-Dawley rats. Morphologic changes of vessel wall were detected by hematoxylin and eosin staining. Molecular and cellular changes, including p120-catenin (p120ctn) and vascular endothelial-cadherin, in the median sagittal section of the artery bifurcation were analyzed by fluorescent staining. RESULTS: Destructive aneurysmal remodeling and the formation of morphologic IAs were observed at the basilar termini of experimental rabbits and the anterior cerebral artery-olfactory artery bifurcation of rats. The expression of p120ctn colocalized with vascular endothelial-cadherin in ECs decreased. Moreover, the expression of p120ctn colocalized with nucleus of ECs increased. These events suggested that p120ctn was transported from the membrane to the nucleus of ECs. CONCLUSIONS: The potential mechanism, that IAs are always localizing in the bifurcation apices, may be that the endothelium injury of vessel wall can be induced by different hemodynamic conditions. Hemodynamic changes in artery bifurcation may initiate the formation of IAs.
Subject(s)
Antigens, CD/metabolism , Cadherins/metabolism , Catenins/metabolism , Endothelial Cells/metabolism , Intracranial Aneurysm/metabolism , Animals , Anterior Cerebral Artery/metabolism , Anterior Cerebral Artery/pathology , Basilar Artery/metabolism , Basilar Artery/pathology , Carotid Artery, Common/surgery , Disease Models, Animal , Endothelial Cells/pathology , Female , Hemodynamics , Intracranial Aneurysm/pathology , Ligation , Male , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Rabbits , Rats , Rats, Sprague-Dawley , Stress, Physiological , Vertebral Artery/metabolism , Vertebral Artery/pathology , Delta CateninABSTRACT
Clazosentan therapy has been found to be effective in reducing the incidence of vasospasm after aneurismal subarachnoid hemorrhage (aSAH). The objective of this meta-analysis was to determine whether different doses of clazosentan treatment significantly reduced the incidence of delayed ischemic neurological deficits (DINDs) and new cerebral infarction (NCI). We systematically searched PubMed, Embase, Cochrane library and Medline from inception until October, 2015. All randomized controlled trials related to the functions of clazosentan in aSAH were included. Analyses were performed following the method guideline of Cochrane Back Review Group. Four randomized placebo-controlled trials met eligibility criteria and enrolled a total of 2159 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk, 0.49 and 95% CI, 0.33-0.73) and NCI (relative risk, 0.42 and 95% CI, 0.25-0.71) in patients treated with a high dose of clazosentan (15 mg/h) after aSAH. In addition, a high dose of clazosentan (15 mg/h) had no more effect on the incidence of adverse events than that of a low dose (1-5 mg/h). The results of the present meta-analysis show that a high dose of clazosentan significantly reduced the incidence of the vasospasm-related DINDs and NCI. Further study is required to fully understand the potential usefulness of clazosentan in patients with aSAH.
Subject(s)
Cerebral Infarction/prevention & control , Dioxanes/administration & dosage , Endothelin A Receptor Antagonists/administration & dosage , Pyridines/administration & dosage , Pyrimidines/administration & dosage , Subarachnoid Hemorrhage/complications , Sulfonamides/administration & dosage , Tetrazoles/administration & dosage , Vasospasm, Intracranial/prevention & control , Cerebral Infarction/epidemiology , Cerebral Infarction/etiology , Dose-Response Relationship, Drug , Humans , Incidence , Randomized Controlled Trials as Topic , Treatment Outcome , Vasospasm, Intracranial/epidemiology , Vasospasm, Intracranial/etiologyABSTRACT
OBJECTIVE: Spontaneous subarachnoid hemorrhage is mostly caused by the rupture of an aneurysm. Neurogenic stunned myocardium (NSM) is one of the most frequent complications caused by aneurysmal subarachnoid hemorrhage (aSAH). The possible pathogenesis of NSM may be that the catecholamine peak resulting from aSAH leads to subendocardial ischemia or coronary artery spasm. We designed this meta-analysis to find out whether beta-blockers (BB) can significantly reduce the incidence of NSM and improve the outcomes of aSAH. PATIENTS AND METHODS: We systematically searched PubMed, Embase, Cochrane library, Elsevier and Medline from inception to Feb 2016. All studies related to the preadmission beta-blocker with aSAH were included. RESULTS: Three retrospective studies and 691 patients were included. The incidence of mortality [OR=0.68, 95%CI (0.08-3.50), P=0.57], cardiac dysfunction [OR = 0.55, 95% CI (0.05-6.49), P=0.63], cerebral vasospasm (OR=0.52 95% CI(0.18-2.56), P=0.50] had no statistical difference between the preadmission BB group and no BB group. CONCLUSION: The preadmission beta-blocker cannot decrease the incidence of mortality, cardiac dysfunction, cerebral vasospasm in patients with aSAH. A further research of the usefulness of preadmission beta-blocker in patients with aSAH will be needed.
