Department of Veterinary Medicine, Nihon University College of Bioresonance Bioresource Science, Kanagawa, Japan.
Tohoku J Exp Med. 2010 Jul;221(3):229-35. doi: 10.1620/tjem.221.229.
Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.
继发性脑损伤（SBD）是由创伤性脑损伤后的细胞凋亡引起的，可分为脑震荡和挫裂伤。脑震荡是头部受到打击后短暂的意识丧失或昏迷，没有病理变化，挫裂伤是伴有出血和广泛外渗的脑损伤。在这项研究中，我们使用大鼠模型研究了脑震荡和挫裂伤后海马区细胞凋亡的时间依赖性变化。我们通过将 3.5 厘米高处的铅块落在硬脑膜上来产生脑震荡，通过烧灼大脑皮层来产生挫裂伤。通过组织病理学分析和测量诱导凋亡性神经元细胞死亡的半胱天冬酶-3 活性来评估 SBD。在脑震荡后 1 小时（约为每个异常的 30%），异常神经元细胞的频率（有空泡或核浓缩或具有 DNA 片段化的）显著高于损伤前水平（0%），并在 48 小时达到最高水平（约为每个异常的 50%），而在脑挫裂伤后 1 小时，异常神经元细胞的频率增加（约 10%），并在 48 小时达到最高水平（约 40%）。同时，在脑震荡后 1 小时，海马体中的半胱天冬酶-3 活性增加了七倍，并在 48 小时内恢复到损伤前水平，而在脑挫裂伤后，半胱天冬酶-3 活性持续增加到 48 小时的最高水平（五倍）。因此，必须在脑震荡后 1 小时内并最晚在脑挫裂伤后 48 小时内进行抗细胞凋亡性死亡治疗，以预防 SBD。
