Post-natal changes in myelination involved in rodent pain processing pathways

Brown/Hathway实验室致力于3R原则，并将其纳入我们的实验室实践。该项目将使用3R方法进行实验程序，使用每种动物的坐骨神经来显著减少研究中使用的大鼠数量，并使用多电极阵列来增加每种动物的数据产量。周围神经面临各种病理情况的风险，包括2型糖尿病、创伤、缺血、周围神经疾病和全身性低血糖。这种病理最重要的功能后果是神经传导受损，可以用电生理技术测量，损伤后传导恢复是神经损伤程度的指标。周围神经可以是混合的运动和感觉，包括有髓(A)和无髓(C)纤维，每种纤维亚型都选择性地对特定的病理敏感。20世纪80年代末，在啮齿类动物的视神经中首次建立了吸力电极模型，此后它被成功地用于研究缺氧和/或血糖对中枢白质损伤的机制。在外周神经中缺乏相同的信息。我们已经展示了一种研究周围神经传导(http://dx.doi.org/10.1113/JP275680)，)的新方法，它允许同时记录A和C纤维。由于这些记录是在相同的实验条件下从同一神经发出的，因此可以在纤维亚型之间进行有意义的比较。这种体外模型可以记录超过8小时的神经传导，因此损伤后/损伤前的传导比率可以提供一个模型，用来评估在周围神经挤压和代谢性损伤模型中临床相关神经保护策略的益处。该项目的目标是：a.建立神经对血糖升高条件的反应，并确定代谢相关底物在支持条件下的能力。确定雪旺细胞在将乳酸传递给轴突(无论是A纤维还是C纤维)中所扮演的角色的任何差异。RICH L R&Brown A M.纤维亚型的特异性传导揭示了小鼠坐骨神经的代谢功能。《生理学杂志》596.10(2018年)第1795-1812页

The Brown/Hathway laboratories are dedicated to the principles of the 3Rs, which are incorporated into our laboratory practices. This project will use a 3Rs approach to the experimental procedures, using both sciatic nerves from each animal to significantly reduce the number of rats used in the study and multielectrode arrays to increase the yield of data from each animal. Peripheral nerves are at risk from a variety of pathological conditions including type 2 diabetes, trauma, ischaemia, peripheral neuropathies and systemic hypoglycaemia. The most important functional consequence of such pathology is impaired nerve conduction, which can be measured using electrophysiological techniques, with post insult recovery of conduction an indicator of the degree of injury incurred by the nerve. Peripheral nerves can be mixed motor and sensory comprising both myelinated (A) and unmyelinated (C) fibres, with each fibre sub-type selectively susceptible to particular pathologies. The suction electrode model was initially developed in the rodent optic nerve in the late 1980s, since when it has successfully been used to study the mechanisms of anoxic and/or aglycemia injury to central white matter. Equivalent information in peripheral nerves is lacking. We have demonstrated a new approach to studying peripheral nerve conduction (http://dx.doi.org/10.1113/JP275680), which allows simultaneous recording of the A and C fibres. Since these recordings emanate from the same nerve under identical experimental conditions meaningful comparisons can be made between fibre sub-types. This in vitro model can be used to record nerve conduction for over 8 hours, thus the ratio of post/pre insult conduction can provide a model with which to assess the benefits of clinically relevant neuroprotective strategies in models of both crush and metabolic injury to peripheral nerves. The aims of the project are:a. Establish the response of the nerves to exposure to aglycaemic conditions and determine the ability of metabolically relevant substrates in supporting conditionb. Establish any differences in the role of Schwann cells in passing lactate to the axons be it A or C fibres.RICH L R & BROWN A M. Fibre sub-type specific conduction reveals metabolic function in mouse sciatic nerve. Journal of Physiology 596.10 (2018) p.1795-1812