Yingfeng Wan, Qing Xie, Ya Hua, Guohua Xi, Richard F Keep, Aditya Pandey
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引用次数: 0
Abstract
Background: Intracerebral hemorrhage (ICH) often impacts patient white matter. However, preclinically, the effects of ICH are mostly studied in rodents with sparse white matter. This study used a lobar porcine ICH model to examine differences in the effects of ICH on white and gray matter as well as the role of the iron chelator deferoxamine (DFX), on attenuation of such injury.
Methods: This two-part study was performed in piglets. Firstly, piglets had a needle (Sham) or 2.5 ml blood injection (ICH) and were euthanized at day 3. Secondly, animals were treated with vehicle or DFX after ICH and were euthanized at day 3. White and gray matter edema, the number of oligodendrocytes (mature and immature) and neurons, and the number of Perls' (iron), ferritin and heme oxygenase (HO)-1 positive cells were examined.
Results: At day 3, ICH induced greater edema formation in white than gray matter. This marked white matter edema was associated with a loss of mature, but not immature, oligodendrocytes. ICH also induced neuronal death in gray matter. There were also marked increases in Perls', ferritin and HO-1 positive cells after ICH in both white and gray matter, but significantly more in the former. DFX attenuated ICH-induced brain edema in white but not gray matter and this was associated with increased survival of mature oligodendrocytes. DFX also increased survival of neurons in the gray matter and it reduced the number of Perls', ferritin and HO-1 positive cells in both tissue types.
Conclusions: While there were commonalities in perihematomal changes between white and gray matter after ICH, there was greater edema in white matter which may be linked to the susceptibility of mature oligodendrocytes to ICH injury. Similarly, while DFX reduced perihematomal iron overload in both white and gray matter, it only significantly reduced edema in white matter where it increased the number of mature oligodendrocytes.
背景:脑出血(ICH)通常会影响患者的白质。然而,临床前大多是在白质稀少的啮齿类动物中研究 ICH 的影响。本研究使用猪叶 ICH 模型来研究 ICH 对白质和灰质影响的差异,以及铁螯合剂去铁胺(DFX)对减轻这种损伤的作用:这项研究以仔猪为对象,由两部分组成。首先,对仔猪进行针刺(Sham)或 2.5 毫升血液注射(ICH),并在第 3 天实施安乐死。其次,动物在 ICH 后接受药物或 DFX 治疗,并在第 3 天安乐死。对白质和灰质水肿、少突胶质细胞(成熟和未成熟)和神经元的数量、Perls'(铁)、铁蛋白和血红素加氧酶(HO)-1阳性细胞的数量进行了检测:结果:在第 3 天,ICH 引起的白质水肿大于灰质水肿。这种明显的白质水肿与成熟少突胶质细胞(而非未成熟少突胶质细胞)的丧失有关。ICH 还诱导灰质中神经元的死亡。ICH 后,白质和灰质中的 Perls'、铁蛋白和 HO-1 阳性细胞也明显增加,但前者明显增加更多。DFX 可减轻 ICH 引起的白质脑水肿,但不能减轻灰质脑水肿,这与成熟少突胶质细胞存活率增加有关。DFX还提高了灰质中神经元的存活率,并减少了两种组织类型中Perls'、铁蛋白和HO-1阳性细胞的数量:结论:虽然 ICH 后白质和灰质的血肿周围变化有共同之处,但白质的水肿更严重,这可能与成熟的少突胶质细胞易受 ICH 损伤有关。同样,虽然 DFX 能减轻白质和灰质血肿周围的铁超载,但它只能显著减轻白质的水肿,因为它能增加成熟少突胶质细胞的数量。
期刊介绍:
Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.