缺血性脑卒中后血管生成模式在对照组与糖尿病大鼠中不同：与脑卒中恢复的相关性。
Vascularization pattern after ischemic stroke is different in control versus diabetic rats: relevance to stroke recovery.
机构信息
From the Department of Physiology, Charlie Norwood Veterans Administration Medical Center, Augusta, GA (R.P., W.L., S.C.F., A.E.); Program in Clinical and Experimental Therapeutics, University of Georgia College of Pharmacy, Augusta, GA (R.P., S.C.F., A.E.); and Departments of Physiology (W.L., Z.Q., A.E.), and Biostatistics (M.A.J.), Georgia Regents University, Augusta, GA.
出版信息
Stroke. 2013 Oct;44(10):2875-82. doi: 10.1161/STROKEAHA.113.001660. Epub 2013 Aug 6.
BACKGROUND AND PURPOSE
Pre-existing diabetes mellitus worsens brain functionality in ischemic stroke. We have previously shown that type 2 diabetic rats exhibit enhanced dysfunctional cerebral neovascularization and when these rats are subjected to cerebral ischemic reperfusion injury develop hemorrhagic transformation and greater neurological deficits. However, our knowledge of vascular and functional plasticity during the recovery phase of diabetic stroke is limited. This study tested the hypothesis that vascular repair is impaired in the poststroke period in diabetes mellitus, and this is associated with poor sensorimotor and cognitive function. We further hypothesized that glycemic control prevents impaired vascularization and improves functional outcome in diabetes mellitus.
METHODS
Vascularization was assessed in the ipsilateral and contralateral hemispheres in control, diabetes mellitus and diabetes mellitus plus metformin groups 14 days after ischemic reperfusion injury, as well as in respective sham controls. Three-dimensional reconstruction of the fluorescein isothiocyanate (FITC)-stained vasculature was achieved by confocal microscopy, and stereological parameters, including vascular volume and surface area, were measured. Astrogliosis was determined by glial fibrillary acidic protein staining. The relative rates of sensorimotor recovery, cognitive decline, and spontaneous activity were assessed.
RESULTS
Vascular density in the peri-infarct area was significantly reduced in diabetes mellitus, whereas there was reparative neovascularization in control rats. Astroglial swelling and reactivity were more pronounced in diabetic stroke compared with control stroke. Diabetes mellitus blunted sensorimotor recovery and also exacerbated anxiety-like symptoms and cognitive deficits. Glycemic control started after stroke partially prevented these changes.
CONCLUSIONS
Diabetes mellitus impairs poststroke reparative neovascularization and impedes the recovery. Glycemic control after stroke can improve neurovascular repair and improve functional outcome.
背景与目的
糖尿病会加重缺血性脑卒中患者的脑功能障碍。我们之前已经发现，2 型糖尿病大鼠表现出增强的功能性脑血管新生障碍，而当这些大鼠发生脑缺血再灌注损伤时，则会发生出血性转化和更严重的神经功能缺损。然而，我们对糖尿病卒中后恢复阶段的血管和功能重塑的了解有限。本研究检验了以下假说，即在糖尿病中，卒中后血管修复受损，这与感觉运动和认知功能不良有关。我们进一步假设，血糖控制可预防血管生成受损并改善糖尿病的功能预后。
方法
在缺血再灌注损伤后 14 天，通过共聚焦显微镜评估对照组、糖尿病组和糖尿病加二甲双胍组的患侧和对侧半球的血管生成情况，以及各自的假手术对照组。通过荧光素异硫氰酸酯（FITC）染色的血管三维重建，测量血管体积和表面积等体视学参数。通过胶质纤维酸性蛋白染色来确定星形胶质细胞的肿胀和反应性。评估感觉运动恢复、认知下降和自发活动的相对速率。
结果
糖尿病组梗死周围区域的血管密度明显降低，而对照组大鼠则出现修复性新生血管。与对照组卒中相比，糖尿病卒中的星形胶质细胞肿胀和反应性更为明显。糖尿病使感觉运动恢复减弱，并加重焦虑样症状和认知缺陷。卒中后开始的血糖控制部分预防了这些变化。
结论
糖尿病会损害卒中后的修复性血管新生，并阻碍恢复。卒中后血糖控制可以改善神经血管修复并改善功能预后。
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