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用SR49059进行治疗后可改善小鼠脑出血性中风后的预后。

Post-treatment with SR49059 improves outcomes following an intracerebral hemorrhagic stroke in mice.

作者信息

Manaenko Anatol, Fathali Nancy, Khatibi Nikan H, Lekic Tim, Shum Kenneth J, Martin Robert, Zhang John H, Tang Jiping

机构信息

Department of Physiology and Pharmacology, Loma Linda University, School of Medicine, Loma Linda, CA 92354, USA.

出版信息

Acta Neurochir Suppl. 2011;111:191-6. doi: 10.1007/978-3-7091-0693-8_32.

Abstract

Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by severe brain edema formation leading to cerebral blood flow compromise and parenchymal damage. Arginine vasopressin (AVP), a non-peptide antidiuretic hormone, has recently been implicated as a modulator of brain edema following injury. In this study, we investigated the effects of SR49059, a highly specific AVP V1a receptor antagonist, on brain injury outcomes following ICH, specifically assessing the ability of SR49059 in reducing brain edema and improving neurobehavioral deficits. Male CD1 mice (n=35) were randomly assigned to the following groups: sham, ICH, ICH with SR49059 at 0.5 mg/kg, and ICH with SR49059 at 2 mg/kg. ICH was induced by using the collagenase injection model, and treatment was given 1 h after surgery. Post-assessment was conducted at 24 and 72 h after surgery, and included brain water content and neurobehavioral testing. The study found that SR49059 significantly reduced cerebral edema at 24 and 72 h post-ICH injury and improved neurobehavioral deficits at 72 h. Our study suggests that blockage of the AVP V1a receptor is a promising treatment target for improving ICH-induced brain injury. Further studies will be needed to confirm this relationship and determine future clinical direction.

摘要

脑出血(ICH)是一种破坏性的中风亚型,其特征是严重的脑水肿形成,导致脑血流受损和实质损伤。精氨酸加压素(AVP),一种非肽类抗利尿激素,最近被认为是损伤后脑水肿的调节因子。在本研究中,我们研究了高度特异性的AVP V1a受体拮抗剂SR49059对脑出血后脑损伤结局的影响,特别评估了SR49059减轻脑水肿和改善神经行为缺陷的能力。将雄性CD1小鼠(n = 35)随机分为以下几组:假手术组、脑出血组、0.5 mg/kg SR49059脑出血组和2 mg/kg SR49059脑出血组。采用胶原酶注射模型诱导脑出血,并在手术后1小时给予治疗。在手术后24小时和72小时进行评估,包括脑含水量和神经行为测试。研究发现,SR49059在脑出血损伤后24小时和72小时显著减轻脑水肿,并在72小时改善神经行为缺陷。我们的研究表明,阻断AVP V1a受体是改善脑出血所致脑损伤的一个有前景的治疗靶点。需要进一步的研究来证实这种关系并确定未来的临床方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/596c/3563694/b276f248243d/nihms438224f1.jpg

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