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首页> 外文期刊>The European Journal of Neuroscience >Phagocytic microglial phenotype induced by glibenclamide improves functional recovery but worsens hyperalgesia after spinal cord injury in adult rats
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Phagocytic microglial phenotype induced by glibenclamide improves functional recovery but worsens hyperalgesia after spinal cord injury in adult rats

机译：格列本脲诱导的吞噬性小胶质细胞表型改善了成年大鼠脊髓损伤后的功能恢复，但加重了痛觉过敏

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Microglial cell plays a crucial role in the development and establishment of chronic neuropathic pain after spinal cord injuries. As neuropathic pain is refractory to many treatments and some drugs only present partial efficacy, it is essential to study new targets and mechanisms to ameliorate pain signs. For this reason we have used glibenclamide (GB), a blocker of KATP channels that are over expressed in microglia under activation conditions. GB has already been used to trigger the early scavenger activity of microglia, so we administer it to promote a better removal of dead cells and myelin debris and support the microglia neuroprotective phenotype. Our results indicate that a single dose of GB (1 μg) injected after spinal cord injury is sufficient to promote long-lasting functional improvements in locomotion and coordination. Nevertheless, the Randall-Selitto test measurements indicate that these improvements are accompanied by enhanced mechanical hyperalgesia. In vitro results indicate that GB may influence microglial phagocytosis and therefore this action may be at the basis of the results obtained in vivo. Injury to CNS involves an initial microgliosis followed by a more persistent astrogliosis. Ideally, both populations might come back to their resting phenotypes once the lesion is repaired and neuroinflammation is resolved. Spinal cord injuries usually imply an abnormally persistent glial activation, which contributes to the detrimental effects of the secondary phase, such as hyperexcitability and neuropathic pain. Our treatment with GB is aimed to trigger the initial activation of microglia in order to better scavenge all the myelin and cell debris just after the contusion. Indeed, GB promotes a minor infiltration of macrophage and microglia, but with an enhanced phagocytic phenotype. This results as a better functional performance, better tissular preservation, but also a worsening in neuropathic pain signs.
机译：小胶质细胞在脊髓损伤后慢性神经性疼痛的发生和建立中起着至关重要的作用。由于神经性疼痛对许多治疗方法都是难治性的，并且某些药物仅显示部分疗效，因此研究缓解疼痛症状的新靶标和机制至关重要。因此，我们使用了格列本脲（GB），一种在激活条件下在小胶质细胞中过度表达的KATP通道阻滞剂。 GB已被用于触发小胶质细胞的早期清除剂活性，因此我们对其进行管理以促进更好地清除死细胞和髓鞘碎片，并支持小胶质细胞的神经保护表型。我们的结果表明，脊髓损伤后单次注射GB（1μg）足以促进运动和协调能力的长期改善。尽管如此，Randall-Selitto测试结果表明，这些改善伴随着机械痛觉过敏的增强。体外结果表明GB可能影响小胶质细胞的吞噬作用，因此该作用可能是体内获得结果的基础。中枢神经系统损伤涉及最初的小胶质细胞增生，然后是更持久的星形胶质增生。理想情况下，一旦病灶修复并且神经炎症得到解决，这两个人群都可能会恢复到其静止的表型。脊髓损伤通常意味着异常持续的神经胶质细胞活化，这会导致继发期的有害影响，例如过度兴奋和神经性疼痛。我们对GB的治疗旨在触发小胶质细胞的初始活化，以便在挫伤后更好地清除所有髓磷脂和细胞碎片。实际上，GB促进了巨噬细胞和小胶质细胞的少量浸润，但吞噬细胞表型增强。这导致更好的功能表现，更好的组织保存，还使神经性疼痛症状恶化。

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