Lack of a gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model
Lack of a gender difference in post-traumatic neurodegeneration in the mouse controlled cortical impact injury model
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DOI：
10.1089/neu.2005.22.669
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发表时间：
2005-06-01
影响因子：
4.2
通讯作者：
Pavel, KM
中科院分区：
文献类型：
--
作者：
Hall, ED;Gibson, TR;Pavel, KM
最近的研究使用小鼠模型的重量下降诱导的“弥漫性”创伤性脑损伤（TBI）已经证明了一个严重的损伤后的创伤后神经退行性变的时间过程和幅度的显着性别差异。通过de Olmos氨基铜银染色法评估，雄性小鼠的最大损伤时间发生在72 h，而雌性小鼠直到14 d才观察到神经退行性变的峰值，并且与雄性小鼠相比，其幅度较小。这种有利于女性的差异被认为与雌激素和孕激素的神经保护作用有关。在目前报道的实验中，我们使用与“弥漫性”TBI研究中所用的相同的品系（CF-1）和重量（29-31 g），比较了在严重水平的“局灶性”受控皮质撞击（CCI; 1 mm，3.5 m/sec）TBI后雄性和雌性小鼠中神经变性的时程和峰值。在24、48和72 h以及1、2和4周时使用图像分析方法测量银染色的体积。在雄性和雌性小鼠中，在24 h时观察到神经变性显著增加，并且两种性别之间的体积没有显著差异。在两个性别组中，在损伤后48 h观察到最大的神经变性。尽管雌性小鼠表现出平均银染色体积更高的趋势，但与雄性小鼠相比，该差异无显著性差异。此外，48小时和4周之间的染色消退率相似。然而，在第4周时，与假手术、非损伤雌性动物相比，损伤雌性动物仍表现出显著更高的染色体积，而在该时间点，假手术和损伤雄性动物之间的染色体积差异不再显著。这些结果表明，在“局灶性”CCI之后，与“弥漫性”损伤范例相比，没有有利于女性的性别差异。两种模型中性别效应之间的差异可能是由于这样的事实，即在“局灶性”CCI模型中，创伤后神经变性的时间比在“弥漫性”模型中看到的明显更快，这可能压倒雌激素和孕激素的神经保护作用，并掩盖了性别差异的外观。
Recent studies using a mouse model of weight-drop-induced "diffuse" traumatic brain injury (TBI) have demonstrated a substantial gender difference in the time course and magnitude of post-traumatic neurodegeneration following a severe level of injury. The time of maximal damage, as assessed by the de Olmos aminocupric silver staining method, occurred at 72 h in male mice, whereas the peak of neurodegeneration was not observed until 14 days in females and was less in magnitude compared to males. This difference, favoring females, has been postulated to relate to the neuroprotective actions of estrogen and progesterone. In the presently reported experiments, we compared the time course and peak of neurodegeneration in male and female mice after a severe level of "focal" controlled cortical impact (CCI; I mm, 3.5 m/sec) TBI using the same strain (CF-1) and weight (29-31 g) as employed in the "diffuse" TBI study. The volume of silver staining was measured using image analysis methods at 24, 48, and 72 h, and 1, 2 and 4 weeks. In male and female mice, a significant increase in neurodegeneration was observed at 24 h, and the volume was not significantly different between the two genders. In both gender groups, the maximal neurodegeneration was seen at 48 h after injury. Although the female mice exhibited a trend toward higher mean volumes of silver staining, this difference was not significantly different compared to males. Furthermore, the rate of resolution of staining between 48 h and 4 weeks was similar. However, injured females still exhibited a significantly higher volume of staining compared to sham, non-injured females at 4 weeks, whereas the difference in staining volume between sham and injured males was no longer significant at that time point. These results show that, following a "focal" CCI, there is no gender difference that favors females, in contrast to that seen with the "diffuse" injury paradigm. The disparity between the effects of gender in the two models may be due to the fact that, in the "focal" CCI model, the timing of post-traumatic neurodegeneration is significantly more rapid than that seen in the "diffuse" model, which may overwhelm the neuroprotective effects of estrogen and progesterone and obscure the appearance of a gender difference.