M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly
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X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). 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Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). 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引用次数: 0
摘要
大脑在微量元素组成方面是一个特殊的器官,并保持着一个强大的屏障系统,将这一特殊环境与身体其他部位和血管系统隔绝开来。脑卒中是由于大脑某一区域失去充足的血流而引起的。如果没有足够的血流,缺血性变化几乎立即开始,引发缺血级联反应,其特点是离子失调、功能丧失、氧化损伤、细胞退化以及有助于维持这种环境的屏障被破坏。离子失调是中风病理生理学的一个标志,我们观察到中风后大脑中的大多数元素都失调了。基于 X 射线荧光技术对中风后神经金属组生理变化的检测显示,病变部位和周围组织内的离子严重失调。不仅大多数元素在中风后明显失调,而且失调的程度无法从细胞水平的失调描述中预测。X 射线荧光成像显示,中风病灶的保留率分别为 400%、>200% 和 >150%)。我们推测,中风后血脑屏障的减弱允许元素顺着浓度梯度自由扩散,从而使中风病灶与血液(以及含有脑间质和脑脊液的区室)处于平衡状态。观察到的神经金属组的变化可能会对挽救梗死组织的潜力产生影响,同时也为治疗提供了特定的目标。
X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.
The brain is a privileged organ with regard to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischaemic changes begin almost immediately, triggering an ischaemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and breakdown of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains <25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and >150%, respectively). We hypothesize that weakening of the blood-brain barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The change observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.