Retinal vascular recovery revealed by retinal imaging following neonatal hypoxia ischemia in mice: Is there a role for tyrosine kinase receptor modulation?
Retinal vascular recovery revealed by retinal imaging following neonatal hypoxia ischemia in mice: Is there a role for tyrosine kinase receptor modulation?
复制标题
在小鼠新生儿缺血后，视网膜成像揭示了视网膜血管恢复：酪氨酸激酶受体调节是否有作用？
DOI：
10.1016/j.brainres.2022.148093
复制
发表时间：
2022-12-01
期刊：
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
新生儿缺氧缺血性脑病（HIE）继发于围产期窒息，导致长期视力残疾。新生儿缺氧缺血性脑病的扩张视网膜检查是一种新兴的诊断工具，但缺氧缺血（HI）相关的视网膜血管损伤的表型尚不清楚。7，8-二羟基黄酮（7，8-DHF）是一种TrkB激动剂，对HI相关的脑损伤具有保护作用。我们研究了新生儿HIE小鼠模型的视网膜血管和7，8-DHF在改善HI相关视网膜血管损伤中的功效。出生后第9天（P）的C57 BL 6/J小鼠接受单侧左颈动脉结扎，随后暴露于10%氧气中50分钟。每天腹腔内给予磷酸盐缓冲盐水或7，8-DHF（5 mg/kg），持续7天。研究了未处理或仅颈动脉结扎的小鼠的对照组。在急性（暴露后2周）和慢性（暴露后4周）时间点进行血管造影。定量视网膜动脉宽度、视网膜静脉宽度和侧支血管长度。单独结扎颈总动脉在急性和慢性时间点引起视网膜动脉扩张，但对视网膜静脉没有影响。在急性时间点，HI引起视网膜动脉血管舒张增加，但被7，8-DHF逆转。HI引起同侧眼短侧支血管形成，经7，8-DHF治疗后恢复。视网膜动脉血管舒张和侧支血管的形成，由于HI被拯救的7，8-DHF治疗。视网膜和侧支血管监测可作为HI严重程度的诊断生物标志物。阐明7，8-DHF对视网膜血管作用机制的研究有助于开发新生儿HI的治疗方法。
Hypoxic ischemic encephalopathy (HIE) secondary to perinatal asphyxia leads to long-term visual disabilities. Dilated retinal exams in human newborns with HIE is an emerging diagnostic tool, but phenotypes of hypoxia ischemia (HI) related retinal vascular injury are unclear. 7,8-Dihydroxyflavone (7,8-DHF) is a TrkB agonist with protective effects on HI-related brain damage. We studied retinal vessels in a mouse model of neonatal HIE and the efficacy of 7,8-DHF in ameliorating HI-related retinal vascular injury. C57BL6/J mice at post-natal day (P) 9 received unilateral left carotid artery ligation followed by exposure to 10 % oxygen for 50 min. Phosphate buffered saline or 7,8-DHF (5 mg/kg) were administered daily for 7 days intraperitoneally. Control groups of naïve or carotid artery ligation only mice were studied. Fluorescein angiography was performed in acute (two weeks post-exposure) and chronic (four weeks post-exposure) time points. Retinal artery width, retinal vein width, and collateral vessel length were quantified. Ligation of the common carotid artery alone caused retinal artery dilation in acute and chronic time points, but had no effect on retinal veins. At acute time point, HI caused increased retinal artery vasodilation, but was reversed by 7,8-DHF. HI caused short collateral vessel formation in ipsilateral eyes, rescued by 7,8-DHF treatment. Retinal artery vasodilation and collateral vessel formation due to HI were rescued by 7,8-DHF treatment. Retinal and collateral vessel monitoring could be diagnostic biomarkers for HI severity. Studies to elucidate mechanisms of 7,8-DHF action on retinal vessels could aid development of therapies for neonatal HI.
登录
查看更多内容
影响因子：
2.4
作者：
Bailey, Alexander M.;O'Neill, Thomas J.;Peirce, Shayn M.
通讯作者：
Peirce, Shayn M.
影响因子：
4.6
作者：
Ghaffari, Siavash;Leask, Richard L.;Jones, Elizabeth A. V.
通讯作者：
Jones, Elizabeth A. V.
影响因子：
6.6
作者：
Cengiz, Pelin;Kleman, Neil;Sun, Dandan
通讯作者：
Sun, Dandan
影响因子：
3.6
作者：
Harris, Nia M.;Ritzel, Rodney;Mancini, Nikolas;Jiang, Yuhang;Yi, Xiang;Manickam, Devika S.;Banks, William A.;Kabanov, Alexander V.;McCullough, Louise D.;Verma, Rajkumar
通讯作者：
Verma, Rajkumar
影响因子：
3.4
作者：
Cikla, Ulas;Chanana, Vishal;Cengiz, Pelin
通讯作者：
Cengiz, Pelin