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Characterisation of Endothelin-1-Induced Intrastriatal Lesions Within the Juvenile and Adult Rat Brain Using MRI and 31P MRS

机译:使用MRI和31P MRS表征青少年和成年大鼠脑内内皮素-1诱导的纹状体内病变

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Improved non-invasive magnetic resonance (MR) characterisation of in vivo models of focal ischaemic insults such as transient ischaemic attack (TIA) and perinatal arterial ischaemic stroke (AIS) may assist diagnosis, outcome prediction and treatment design. The classic middle cerebral artery occlusion (MCAO) model of ischaemic stroke is well documented in MR studies but generates extensive and complex lesions involving an acute inflammatory response and de-occlusion that immediately restores circulation. By contrast, intrastriatal microinjection of the potent vasoconstrictor, endothelin-1 (ET-1), induces a focal, reversible and low-flow ischaemia in the absence of a typical inflammatory response, which gradually restores blood flow over several hours and may be more relevant to TIA and AIS pathology. This study presents the first comprehensive longitudinal MR characterisation of the real-time anatomical [T1-weighted (T1-w)/T2-weighted (T2-w)], pathophysiological [apparent diffusion coefficient (ADC), cerebral blood volume, gadolinium contrast imaging of blood–brain barrier (BBB) integrity] and metabolic [phosphorus magnetic resonance spectroscopy (31P MRS)] evolution of a purely ischaemic ET-1-induced lesion within the juvenile and adult rat brain. ET-1-induced cytotoxic oedema was visualised on T2-w magnetic resonance imaging (MRI), inconsistent with the conventional notion that it cannot be detected using anatomical MRI. There was no immunohistochemical evidence of an acute inflammatory response or loss of BBB integrity, thus excluding a vasogenic oedema contribution to the pathology. Maximal T2-w intensity correlated with the lowest ADC value in both age groups, re-emphasising the purely ischaemic nature of the lesion and the absence of vasogenic oedema. Furthermore, extensive acute T1-w hypointensity was observed in the presence of cytotoxic oedema-induced T2-w changes, whereas other authors have shown that increased T1 values following MCAO reflect vasogenic oedema. Intriguingly, the lesion border exhibited hyperintensity on T2-w and ADC MRI at later time points, and the former may be a consequence of phagocytosis-induced fatty droplet deposition by macrophages detected immunohistochemically. In spite of a chronically reduced ADC, typically associated with ischaemia-induced energy failure, a 31P MRS-detectable reduction in the phosphocreatine (PCr) to gamma adenosine triphosphate (γATP) ratio was not observed at any time point in either age group, suggesting dissociation of tissue water diffusion and metabolic changes within the ET-1-induced lesion.
机译:局灶性缺血损伤的体内模型(例如短暂性缺血发作(TIA)和围产期动脉缺血性卒中(AIS))的改进的非侵入性磁共振(MR)表征可能有助于诊断,结果预测和治疗设计。 MR研究已充分证明了经典的缺血性中风大脑中动脉闭塞(MCAO)模型,但会产生广泛而复杂的病变,涉及急性炎症反应和解除阻塞,可立即恢复血液循环。相比之下,在没有典型的炎症反应的情况下,有效血管收缩剂内皮素-1(ET-1)的纹状体内显微注射可引起局灶性,可逆性和低流量缺血,这种炎症反应可在数小时内逐渐恢复血流,并且可能更多。与TIA和AIS病理学有关。这项研究提出了实时解剖学[T1加权(T1-w)/ T2加权(T2-w)],病理生理学[表观扩散系数(ADC),脑血容量,contrast对比剂]的首次全面纵向MR表征。血脑屏障(BBB)完整性成像]和代谢[磷磁共振波谱(31P MRS)]在少年和成年大鼠脑内发生的纯缺血性ET-1诱发病变的演变。在T2-w磁共振成像(MRI)上可以看到ET-1诱导的细胞毒性水肿,这与传统的无法使用解剖MRI检测到的观念相矛盾。没有免疫组织化学证据显示急性炎症反应或BBB完整性丧失,因此排除了血管性水肿对病理的影响。在两个年龄组中,最大的T2-w强度与最低的ADC值相关,这再次强调了病变的纯粹缺血性和无血管性水肿。此外,在存在细胞毒性水肿引起的T2-w变化的情况下,观察到广泛的急性T1-w低血压,而其他作者已经表明,MCAO后T1值升高反映了血管性水肿。有趣的是,病变边界在稍后的时间点在T2-w和ADC MRI上表现出高强度,而前者可能是吞噬作用诱导的免疫组织化学检测的巨噬细胞脂肪滴沉积的结果。尽管ADC长期降低,通常与缺血引起的能量衰竭有关,但在任何年龄段的任何时间点均未观察到磷酸肌酸(PCr)与γ-三磷酸腺苷(γATP)之比的31P MRS可检测到的降低,表明ET-1诱导的病变内组织水扩散和代谢变化的解离。

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