Hamilton B F, Gould D H
Acta Neuropathol. 1987;72(3):286-97. doi: 10.1007/BF00691103.
The clinical signs and morphological brain lesions associated with histotoxic hypoxia induced by subcutaneous injection of 3-nitropropionic acid (NPA) in rats are described, and compared to hypoxic brain damage from other causes including ischemia and hypoglycemia. The brains were perfusion-fixed with paraformaldehyde/glutaraldehyde fixative, and examined by light and electron microscopy. Intoxicated rats developed severe neurological disease characterized by somnolence, uncoordinated gait with stereotypical paddling movements, and ventral or lateral recumbency. Recumbent rats had a selective, bilaterally symmetrical pattern of severe morphological injury in the caudate-putamen, hippocampus, and thalamus. Recumbency was a consistent indicator of the development of morphological brain lesions. In contrast to reports describing rat models of ischemia and hypoglycemia, morphological injury was not seen in the cerebral and cerebellar cortices of NPA-intoxicated rats. Ultrastructurally, neuronal alterations ranged from chromatin clumping with increased cytoplasmic lucency to severe cellular shrinkage or swelling with marked mitochondrial swelling (high amplitude swelling). White matter alterations included axonal swelling and adaxonal splitting of myelin lamellae. Vascular changes included perivascular deposits of proteinaceous material presumably from leakage of serum proteins, variable electron lucency of endothelial cell cytoplasm, an apparent increase in pinocytotic vesicles, rare platelet thrombosis of capillaries, and rare intravascular blebs of luminal plasma membrane. As a model of brain damage following energy deficiency, NPA intoxication has the advantages of producing morphological brain injury in a highly predictable anatomical pattern, and at a time paralleling the onset of clinical recumbency.
描述了皮下注射3-硝基丙酸（NPA）诱导大鼠组织中毒性缺氧相关的临床体征和脑形态学损伤，并与包括缺血和低血糖在内的其他原因导致的缺氧性脑损伤进行了比较。用多聚甲醛/戊二醛固定剂对大脑进行灌注固定，并通过光镜和电镜检查。中毒大鼠出现严重的神经疾病，表现为嗜睡、步态不协调并伴有刻板划水动作，以及腹侧或侧卧位。卧位大鼠在尾状核-壳核、海马体和丘脑出现了选择性的、双侧对称的严重形态学损伤模式。卧位是脑形态学损伤发展的一个一致指标。与描述缺血和低血糖大鼠模型的报告不同，NPA中毒大鼠的大脑皮质和小脑皮质未出现形态学损伤。超微结构上，神经元改变范围从染色质凝聚伴细胞质透明度增加到严重的细胞萎缩或肿胀并伴有明显的线粒体肿胀（高幅度肿胀）。白质改变包括轴突肿胀和髓鞘板层的轴突旁分裂。血管变化包括血管周围蛋白质物质沉积（推测来自血清蛋白渗漏）、内皮细胞细胞质电子透明度可变、吞饮小泡明显增多、毛细血管罕见血小板血栓形成以及管腔质膜罕见血管内泡状突起。作为能量缺乏后脑损伤的模型，NPA中毒具有以高度可预测的解剖模式产生脑形态学损伤的优点，且损伤时间与临床卧位的开始时间一致。
