Jacobsen Marianne, Lett Kristen, Barden John Mark, Simpson Gavin L, Buttigieg Josef
Department of Biology, University of Regina, Regina, SK, Canada.
Front Neurol. 2018 Dec 18;9:1107. doi: 10.3389/fneur.2018.01107. eCollection 2018.
Spinal cord injury (SCI) results in significant neuronal and glial cell death resulting in impaired neurological and motor function. Uncontrolled Ca entry results in excitotoxicity and cell death. In this study, we examine the use of a BK channel activator, Isopimaric acid (ISO), as a neuroprotective agent post-SCI as this channel is involved in regulating Ca entry. By using a 25-g clip compression at the T6 level, we generated a SCI event in wistar rats. At 1 h post-injury we administered ISO (BK channel activator), the BK channel inhibitor iberiotoxin (IbTx), or a vehicle control for 4 weeks via mini osmotic pump (pump capacity). For 8 weeks post-injury, gait analysis of motor function was performed. At the end of 8 weeks, the extent of myelination in the spinal cord was assessed in addition to the electrophysiological profile. Our immunohistological data suggests that ISO treatment leads to an increase or preservation of myelinated axonal tracts. This was further supported by our electrophysiological studies which demonstrate higher compound action potential amplitudes and speed of transmission in ISO-treated animals compared to inj-non-treated. Finally, treatment with ISO significantly improved motor function in our test model. In conclusion, activation of the BK channel during acute SCI may be a novel therapeutic target for acute SCI.
脊髓损伤（SCI）会导致大量神经元和胶质细胞死亡，进而造成神经和运动功能受损。不受控制的钙离子内流会导致兴奋性毒性和细胞死亡。在本研究中，我们研究了BK通道激活剂异海松酸（ISO）作为SCI后神经保护剂的用途，因为该通道参与调节钙离子内流。通过在T6水平使用25克夹压法，我们在Wistar大鼠中制造了脊髓损伤事件。在损伤后1小时，我们通过微型渗透泵（泵容量）给予ISO（BK通道激活剂）、BK通道抑制剂iberiotoxin（IbTx）或载体对照，持续4周。在损伤后8周，对运动功能进行步态分析。在8周结束时，除了评估电生理特征外，还评估了脊髓中的髓鞘形成程度。我们的免疫组织学数据表明，ISO治疗可导致有髓轴突束增加或保存。我们的电生理研究进一步支持了这一点，该研究表明，与未治疗的损伤动物相比，ISO治疗的动物具有更高的复合动作电位幅度和传导速度。最后，在我们的测试模型中，ISO治疗显著改善了运动功能。总之，急性脊髓损伤期间BK通道的激活可能是急性脊髓损伤的一个新的治疗靶点。
