Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Departments of Neurosurgery, University of Michigan, Ann Arbor, MI, USA.
Exp Neurol. 2025 Jan;383:115041. doi: 10.1016/j.expneurol.2024.115041. Epub 2024 Nov 1.
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.
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.
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.
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.
脑出血（ICH）常影响患者的白质。然而，在临床前，ICH 的影响主要在白质稀疏的啮齿动物中进行研究。本研究使用大脑叶状猪 ICH 模型，研究 ICH 对白质和灰质的影响差异，以及铁螯合剂地拉罗司（DFX）对减轻这种损伤的作用。
这项两部分的研究在小猪中进行。首先，小猪接受了针（假手术）或 2.5ml 血液注射（ICH），并在第 3 天安乐死。其次，动物在 ICH 后接受载体或 DFX 治疗，并在第 3 天安乐死。检查白质和灰质水肿、少突胶质细胞（成熟和不成熟）和神经元的数量，以及 Perls'（铁）、铁蛋白和血红素加氧酶（HO）-1 阳性细胞的数量。
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的丢失有关，但不成熟少突胶质细胞不受影响。ICH 还导致灰质中的神经元死亡。在白质和灰质中，ICH 后也出现明显的 Perls'、铁蛋白和 HO-1 阳性细胞增多，但前者更为明显。DFX 减轻了 ICH 引起的白质脑水肿，但不减轻灰质脑水肿，这与成熟少突胶质细胞的存活率增加有关。DFX 还增加了灰质神经元的存活率，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。
虽然 ICH 后白质和灰质的血肿周围变化有共同之处，但白质水肿更为明显，这可能与成熟少突胶质细胞对 ICH 损伤的易感性有关。同样，虽然 DFX 减少了白质和灰质的血肿周围铁过载，但它仅显著减少了白质水肿，增加了成熟少突胶质细胞的数量。
