Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?
Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?
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DOI：
10.1046/j.1460-9568.2002.02241.x
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发表时间：
2002-11-01
影响因子：
3.4
通讯作者：
Schwartz, M
中科院分区：
文献类型：
--
作者：
Hauben, E;Mizrahi, T;Schwartz, M
免疫细胞已被证明有助于中枢神经系统（CNS）损伤的自发恢复。在这里，我们发现，成年雌性大鼠和小鼠从不完全脊髓损伤（ISCI）中恢复得明显好于同窝雄性小鼠。在缺乏成熟 T 细胞的成年小鼠中，这种性别二态性被消除，恢复也更差。成年大鼠脊髓挫伤后，在受伤前接受二氢睾酮治疗的雌性大鼠的功能恢复（通过开放视野中的运动评分测量）明显差于安慰剂治疗的对照组，而去势雄性大鼠的功能恢复明显优于未去势雄性同窝小鼠。睾酮受体拮抗剂氟他胺的创伤后给药促进了成年雄性大鼠的功能恢复。这些结果与已知的睾酮对细胞介导的免疫的抑制作用一致，表明雄激素介导的免疫抑制在 ISCI 相关的免疫功能障碍中发挥作用，因此可以部分解释男性 ISCI 的结果比女性更差。我们建议，女性比男性更容易产生自身免疫反应，在中枢神经系统损伤的情况下可以从这种反应中受益。
Immune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery ( measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo-treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post-traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell-mediated immunity, suggest that androgen-mediated immunosuppression plays a role in ISCI-related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults.