Uehara H, Yoshioka H, Kawase S, Nagai H, Ohmae T, Hasegawa K, Sawada T
Department of Pediatrics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Brain Res. 1999 Aug 7;837(1-2):213-20. doi: 10.1016/s0006-8993(99)01675-3.
Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.
脑室周围白质软化是脑性瘫痪的一个重要病因，其特征为脑室周围白质出现囊肿和凝固性坏死。由于尚未在小动物中建立脑室周围白质软化模型，因此期望在未成熟的啮齿动物中建立一种新的白质损伤模型。对5日龄新生大鼠双侧颈动脉进行结扎，并在7日龄时对大脑进行神经病理学检查。在组织学检查的22个大脑中，20个（90.9%）出现白质改变，包括内囊及其周围的凝固性坏死和囊性病变，而只有2个出现小的脑梗死，5个在大脑皮层显示一些缺血性神经元。双侧颈动脉结扎（BCAO）动物的皮质下白质脑血流量（CBF）降至对照组的约25%。淀粉样前体蛋白（APP）免疫组织化学显示内囊和皮质下白质中有各种APP免疫反应性轴突形态，且BCAO大脑的大脑皮层锥体细胞中APP表达更强。这些结果表明，在5日龄大鼠中，当CBF降至约25%时，白质比大脑皮层更易受损，并且表明该模型对于研究新生儿脑低灌注引起的白质变化有用，因为之前新生小鼠和大鼠的缺氧缺血性脑损伤模型显示灰质更易受损。还表明APP是未成熟脑白质中轻度轴突破坏的敏感标志物。
