MRI evaluation of BBB disruption after adjuvant AcSDKP treatment of stroke with tPA in rat.
MRI evaluation of BBB disruption after adjuvant AcSDKP treatment of stroke with tPA in rat.
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DOI：
10.1016/j.neuroscience.2014.04.025
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发表时间：
2014-06-20
期刊：
影响因子：
3.3
通讯作者：
Jiang, Q.
中科院分区：
文献类型：
--
作者：
Ding, G.;Zhang, Z.;Chopp, M.;Li, L.;Zhang, L.;Li, Q.;Wei, M.;Jiang, Q.
tPA溶栓治疗缺血性卒中的主要局限性是出血风险。我们测试了AcSDKP（N-乙酰基-丝氨酰-赖氨酰-脯氨酸）作为辅助治疗剂，以减少卒中的组合tPA溶栓治疗中的血脑屏障（BBB）破坏。将栓塞性卒中的Wistar大鼠随机分为缺血后4 h开始的tPA单药治疗组（n=9）或tPA和AcSDKP联合治疗组（n=9）。在治疗前后进行MRI测量。进行免疫组织化学染色和测量以确认MRI结果。用Gd-DTPA进行的纵向MRI渗透性测量表明，与tPA单药治疗相比，AcSDKP和tPA联合治疗急性栓塞性卒中在3天和6天时显著降低了BBB渗漏（18.3± 9.8mm ~ 3 vs 65.0± 21.0mm ~ 3，p<0.001），治疗前两组血脑屏障渗漏量相当（6.8± 4.4mm ~ 3 vs 4.3± 3.3mm ~ 3，p>0.18）。在联合治疗组中观察到的血脑屏障渗漏的实质性减少与通过T2图测量的缺血性病变的减少密切相关（113.6±24.9mm3 vs 188.1±60.8mm3，p<0.04，在第6天）。相同群体大鼠的组织学分析显示，在中风后6天，与tPA单一疗法相比，组合治疗显著减少了实质纤维蛋白沉积（0.063±0.059mm2对0.172±0.103mm2，p<0.03）和梗塞体积（146.7±35.9mm3对199.3±60.4mm3，p<0.05）。MRI提供了对tPA和AcSDKP联合治疗卒中4小时后的治疗获益的生物学见解，并证明与tPA单药治疗相比，脑血管完整性显著改善，具有神经保护作用。
The primary limitation of thrombolytic treatment of ischemic stroke with tPA is the hemorrhagic risk. We tested AcSDKP (N-acetyl-seryl-aspartyl-lysyl-proline), as an auxiliary therapeutic agent, to reduce blood-brain barrier (BBB) disruption in a combination tPA thrombolytic treatment of stroke. Wistar rats subjected to embolic stroke were randomly assigned to either the tPA monotherapy group (n=9) or combination of tPA and AcSDKP treatment group (n=9) initiated at 4h after ischemia. MRI measurements were performed before and after the treatments. Immunohistochemical staining and measurements were performed to confirm MRI findings. Longitudinal MRI permeability measurements with Gd-DTPA demonstrated that combination treatment of acute embolic stroke with AcSDKP and tPA significantly reduced BBB leakage, compared to tPA monotherapy, at 3 and 6 days (18.3±9.8mm3 vs 65.0±21.0mm3, p<0.001) after onset of stroke, although BBB leakage was comparable between the two groups prior to the treatments (6.8±4.4mm3 vs 4.3±3.3mm3, p>0.18). The substantial reduction of BBB leakage observed in the combination treatment group was closely associated with reduced ischemic lesions measured by T2 maps (113.6±24.9mm3 vs 188.1±60.8mm3, p<0.04 at 6d). Histopathological analysis of the same population rats showed that the combination treatment significantly reduced parenchymal fibrin deposition (0.063±0.059mm2 vs 0.172±0.103mm2, p<0.03) and infarct volume (146.7±35.9mm3 vs 199.3±60.4mm3, p<0.05) compared to the tPA monotherapy at 6 days after stroke. MRI provides biological insight into the therapeutic benefit of combination treatment of stroke with tPA and AcSDKP 4 hours after onset, and demonstrates significantly improved cerebrovascular integrity with neuroprotective effects compared with tPA monotherapy.
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影响因子：
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作者：
Rhaleb, Nour-Eddine;Pokharel, Saraswati;Sharma, Umesh C.;Peng, Hongmei;Peterson, Edward;Harding, Pamela;Yang, Xiao-Ping;Carretero, Oscar A.
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6.3
作者：
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DOI：
10.1097/00004647-199611000-00036
发表时间：
1996-11-01
影响因子：
6.3
作者：
Hamann, GF;Okada, Y;delZoppo, GJ
通讯作者：
delZoppo, GJ