Lozeron Pierre, Mantsounga Chris S, Broqueres-You Dong, Dohan Anthony, Polivka Marc, Deroide Nicolas, Silvestre Jean-Sébastien, Kubis Nathalie, Lévy Bernard I
Angiogenesis and Translational Research Center, INSERM U965, Paris, France.
Clinical Physiology Department, AP-HP, Hôpital Lariboisière, Paris, France.
J Neurosci Res. 2015 Sep;93(9):1451-61. doi: 10.1002/jnr.23597. Epub 2015 May 5.
Neuropathy is the most common complication of the peripheral nervous system during the progression of diabetes. The pathophysiology is unclear but may involve microangiopathy, reduced endoneurial blood flow, and tissue ischemia. We used a mouse model of type 1 diabetes to study parallel alterations of nerves and microvessels following tissue ischemia. We designed an easily reproducible model of ischemic neuropathy induced by irreversible ligation of the femoral artery. We studied the evolution of behavioral function, epineurial and endoneurial vessel impairment, and large nerve myelinated fiber as well as small cutaneous unmyelinated fiber impairment for 1 month following the onset of ischemia. We observed a more severe hindlimb dysfunction and delayed recovery in diabetic animals. This was associated with reduced density of large arteries in the hindlimb and reduced sciatic nerve epineurial blood flow. A reduction in sciatic nerve endoneurial capillary density was also observed, associated with a reduction in small unmyelinated epidermal fiber number and large myelinated sciatic nerve fiber dysfunction. Moreover, vascular recovery was delayed, and nerve dysfunction was still present in diabetic animals at day 28. This easily reproducible model provides clear insight into the evolution over time of the impact of ischemia on nerve and microvessel homeostasis in the setting of diabetes. © 2015 Wiley Periodicals, Inc.
神经病变是糖尿病进展过程中最常见的周围神经系统并发症。其病理生理学尚不清楚，但可能涉及微血管病变、神经内膜血流减少和组织缺血。我们使用1型糖尿病小鼠模型来研究组织缺血后神经和微血管的平行变化。我们设计了一种通过股动脉不可逆结扎诱导的缺血性神经病变的易于复制的模型。我们研究了缺血发作后1个月内行为功能、神经外膜和神经内膜血管损伤以及大神经有髓纤维和小皮肤无髓纤维损伤的演变。我们观察到糖尿病动物的后肢功能障碍更严重且恢复延迟。这与后肢大动脉密度降低和坐骨神经神经外膜血流减少有关。还观察到坐骨神经神经内膜毛细血管密度降低，这与小无髓表皮纤维数量减少和大的有髓坐骨神经纤维功能障碍有关。此外，血管恢复延迟，并且在第28天糖尿病动物中仍存在神经功能障碍。这种易于复制的模型为缺血对糖尿病背景下神经和微血管稳态的影响随时间的演变提供了清晰的见解。© 2015威利期刊公司。
