Differential lumbar spinal cord responses among wild type, CD4 knockout, and CD40 knockout mice in spinal nerve L5 transection-induced neuropathic pain.
Differential lumbar spinal cord responses among wild type, CD4 knockout, and CD40 knockout mice in spinal nerve L5 transection-induced neuropathic pain.
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DOI：
10.1186/1744-8069-8-88
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发表时间：
2012-12-18
期刊：
影响因子：
3.3
通讯作者：
Eurich A
中科院分区：
文献类型：
--
作者：
Cao L;Beaulac H;Eurich A
我们之前的研究表明，腰椎脊髓浸润性CD4+ T细胞和小胶质细胞CD40都有助于维持神经性疼痛脊神经L5横断（L5Tx）小鼠模型的机械超敏反应。为了进一步描述CD4和cd40介导的机制参与l5tx诱导的神经性疼痛行为的发展，我们通过流式细胞术检测了野生型（WT） BALB/c、BALB/c-CD4敲除（KO）和BALB/c- cd40 KO小鼠的腰椎脊髓单个核细胞。在WT小鼠中，L5Tx诱导同侧脊髓中单个核细胞、小胶质细胞（CD45loCD11b+）和浸润性白细胞（CD45hi）的总数显著但短暂（在第3天和/或第7天）增加。在CD4 KO小鼠中，仅在l5tx后第7天检测到小胶质细胞的显著升高，而l5tx后浸润性白细胞未观察到显著增加。CD40 KO小鼠没有表现出WT小鼠中观察到的任何变化。此外，中和CD40抗体治疗表明CD40信号早期参与l5tx诱导的机械性超敏反应的发展。总之，数据表明CD4和CD40都在l5tx诱导的白细胞浸润腰椎脊髓中发挥作用，但在周围神经损伤后脊髓小胶质细胞激活方面有不同的贡献。
Our previous studies have indicated that both lumbar spinal cord-infiltrating CD4+ T cells and microglial CD40 contribute to the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain spinal nerve L5 transection (L5Tx). To further delineate the CD4 and CD40-mediated mechanisms involved in the development of L5Tx-induced neuropathic pain behaviors, we examined the lumbar spinal cord mononuclear cells of wild type (WT) BALB/c, BALB/c-CD4 knockout (KO), and BALB/c-CD40 KO mice via flow cytometry. In WT mice, L5Tx induced significant but transient (at day 3 and/or day 7) increases of the total numbers of mononuclear cells, microglial cells (CD45loCD11b+), and infiltrating leukocytes (CD45hi) in the ipsilateral side of the spinal cord. In CD4 KO mice, significant elevation of microglia was detected only on day 7 post-L5Tx, while no significant increase in infiltrating leukocytes post-L5Tx was observed. CD40 KO mice did not exhibit any of the changes observed in WT mice. Furthermore, neutralizing CD40 antibody treatment indicated an early involvement of CD40 signaling in the development of L5Tx-induced mechanical hypersensitivity. Altogether, data indicate that both CD4 and CD40 play a role in L5Tx-induced leukocyte infiltration into the lumbar spinal cord but have differential contributions to spinal cord microglial activation following peripheral nerve injury.
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影响因子：
9.3
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