Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve.

Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.

Systemic Inflammatory Response and Multiple Organ Dysfunctions Following Crush Injury: a New Experimental Model in Rabbits.

In this study, we aim to develop a new, reproducible crush injury (CI) model in rabbits. Anesthetized rabbits were compressed on both hind limbs using a special instrument for 6 h followed by 3 h of reperfusion. Blood samples and injured muscles were collected for biochemical analysis and morphological evaluation. Survival observation lasted for 72 h. Bilateral compressions with 10 kg/kg body weight (BW), but not with 5 kg/kg BW, reduced serious systemic impairment. Bilateral compressions with 10 kg/kg BW resulted in severe lactic acidosis; increased serum K+, creatine phosphokinase, aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine levels; and a sharply decreased mean arterial blood pressure after compression release. Serious tissue edema and inflammation were observed in the damaged muscles. The mortality rates in compression groups were 20% (5 kg/kg BW) and 60% (10 kg/kg BW). There was a significant increase in plasma concentrations of TNF-α and IL-1ß after compression. Plasma IL-1ß levels returned to control levels at 6 h after compression release, whereas TNF-α peaked at 12 h following reperfusion. Furthermore, antiinflammatory cytokines, including IL-4 and IL-10, were also increased after compression, and these two cytokines peaked at 12 h after compression release. Our data suggested that bilateral compression with 10 kg/kg BW on rabbits' hind limbs is a reproducible CI model, and we also reported the CI-induced systemic inflammatory responses and changes of cytokines over time.