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Precisional controlled mechanical compression for reproducible chronic constriction injury mimicking compressive neuropathy in rat sciatic nerve
Szu han Chen, MD/master1, Yuan-Yu Hsueh, MD/PHD2, Chia-Ching Wu, PHD, Professor2, Tzu-chieh Huang, PHD2 and Jheng-yang Wang, master2, (1)National Cheng Kung University, Tainan, Taiwan, (2)National Cheng-Kung University, Tainan, Taiwan

Introduction



Compressive neuropathy remains high recurring and challenging disease for patients, regardless of surgical decompression. The degree of mechanical compression is correlated to the severity of neurological dysfunction. The current available animal models of chronic constriction injury fail to produce reproducible outcomes in terms of controlled compression forces. We aim to analyze the crucial role of controlled mechanical forces to the functional outcomes of chronic constriction injury.



Materials and methods



Variable degree of compressive forces are manipulated and fine-tuned to generate different degree of chronic constriction injury on rat sciatic nerve. During one month period, serial sensory outcomes are evaluated by the Von Frey test. Muscle atrophy and nerve degeneration are evaluated at 1 month by muscle weight and histologic examination. The degree of neuroinflammation are also investigated to reveal the influential role of compressive forces.



Results



The degree of compressive force significantly correlated to the neuropathological severity in terms of sensory dysfunction and muscle atrophy, with dose dependent effect. High mechanical forces contribute to severe muscle atrophy and hypoesthesia whereas low forces induced mechanical allodynia with better residual muscle reservation. Well-controlled loose forces can constantly contribute to significantly less myelin degradation, less neuroinflammation and scantly macrophage infiltration.



Conclusion



The functional influences of tunable compressive forces recapitulate the diversity of clinical symptoms in compressive neuropathy. This controllable and reproducible model of compressive neuropathy unveils the underlying molecular mechanisms of neural inflammation, leading to develop translational therapeutics for nerve regeneration in the future.
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