Xin Ying, Meng Shu-Zhen
Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004 China.
Zhongguo Dang Dai Er Ke Za Zhi. 2010 Jun;12(6):468-73.
To compare the features of brain injury in neonatal rats with different severities of hypoxia-ischemia (HI), and explore the role of microglial activation and cytokines.
One hundred and twenty 7-day-old rats were randomized to three groups: sham control, mild HI, and severe HI. The rats in the HI groups were subjected to right carotid artery occlusion and 8% oxygen hypoxia exposure (40 minutes, 34.5 Celsius degree in the mild HI group; 65 minutes, 35.5 Celsius degree in the severe HI group). MRI, microtubule associated protein (MAP2) and TUNEL staining were used to confirm the severity of brain injury. Changes in expression of activated microglia (ED1) and signs of cytokine involvement or oxidative stress (TNF-alpha, nitrotyrosine) were assessed immunohistochemically.
In the mild HI group, MRI scans demonstrated increased T2 values in the ipsilateral subcortical white matter and a slight loss of T2 values in the cortex, corresponding to a medium loss of MAP2 in the ipsilateral cortex. There was an increase in the number of TUNEL positive cells compared to the control group within the subcortical white matter. In the severe HI group, the T2 value increased in the majority of the hemisphere, corresponding to a severe loss of staining for MAP2 in the ispilateral hemisphere. The number of TUNEL positive cells significantly increased in the ipsilateral cortex and white matter. In the mild HI group, ED1, TNF-alpha and nitrotyrosine expression increased only in the acute stage and was only observed in subcortical white matter. In contrast, after severe HI, the increase in ED1, TNF-alpha and nitrotyrosine expression was observed in the whole ipsilateral hemisphere and prolonged for weeks.
Following a mild HI a relatively selective white matter injury compares to the pannecrosis in the cortex and white matter following a severe HI. Microglial activation and over-expression of cytokines might contribute to the development of hypoxic-ischemic brain damage.
比较不同严重程度缺氧缺血（HI）新生大鼠脑损伤的特征，并探讨小胶质细胞激活和细胞因子的作用。
将120只7日龄大鼠随机分为三组：假手术对照组、轻度HI组和重度HI组。HI组大鼠接受右颈动脉结扎并暴露于8%氧气低氧环境（轻度HI组40分钟，34.5摄氏度；重度HI组65分钟，35.5摄氏度）。采用MRI、微管相关蛋白（MAP2）和TUNEL染色来确定脑损伤的严重程度。免疫组织化学法评估活化小胶质细胞（ED1）表达的变化以及细胞因子参与或氧化应激的迹象（TNF-α、硝基酪氨酸）。
在轻度HI组中，MRI扫描显示同侧皮质下白质T2值升高，皮质T2值略有降低，对应同侧皮质中MAP2中度丢失。与对照组相比，皮质下白质内TUNEL阳性细胞数量增加。在重度HI组中，大部分半球T2值升高，对应同侧半球MAP2染色严重丢失。同侧皮质和白质中TUNEL阳性细胞数量显著增加。在轻度HI组中，ED1、TNF-α和硝基酪氨酸表达仅在急性期增加，且仅在皮质下白质中观察到。相反，重度HI后，ED1、TNF-α和硝基酪氨酸表达在同侧整个半球均增加，并持续数周。
与重度HI后皮质和白质的全层坏死相比，轻度HI后出现相对选择性的白质损伤。小胶质细胞激活和细胞因子的过度表达可能有助于缺氧缺血性脑损伤的发展。
