Changes in the blood-nerve barrier after sciatic nerve cold injury: indications supporting early treatment

Abstract

Severe edema in the endoneurium can occur after non-freezing cold injury to the peripheral nerve, which suggests damage to the blood-nerve barrier. To determine the effects of cold injury on the blood-nerve barrier, the sciatic nerve on one side of Wistar rats was treated with low temperatures (3–5°C) for 2 hours. The contralateral sciatic nerve was used as a control. We assessed changes in the nerves using Evans blue as a fluid tracer and morphological methods. Excess fluid was found in the endoneurium 1 day after cold injury, though the tight junctions between cells remained closed. From 3 to 5 days after the cold injury, the fluid was still present, but the tight junctions were open. Less tracer leakage was found from 3 to 5 days after the cold injury compared with 1 day after injury. The cold injury resulted in a breakdown of the blood-nerve barrier function, which caused endoneurial edema. However, during the early period, the breakdown of the blood-nerve barrier did not include the opening of tight junctions, but was due to other factors. Excessive fluid volume produced a large increase in the endoneurial fluid pressure, prevented liquid penetration into the endoneurium from the microvasculature. These results suggest that drug treatment to patients with cold injuries should be administered during the early period after injury because it may be more difficult for the drug to reach the injury site through the microcirculation after the tissue fluid pressure becomes elevated.

Pathophysiological Changes of Physical Barriers of Peripheral Nerves After Injury

“…For example, after cryogenic injury, horseradish peroxidase enzyme substrate complex was observed in both endoneurium and vessel lumens in rats injected with horseradish peroxidase into the jugular vein ( Myers et al, 1981 ). Treating rat sciatic nerves with low temperatures (3–5°C) for 2 h would lead to non-freezing cold injury and result in the leakage of fluid tracer Evans blue in endoneurium, breakdown of the blood-nerve barrier, and severe edema in endoneurium ( Li et al, 2015 ). Notably, it was demonstrated that the opening of tight junctions occurred at a later time point than the leakage of Evans blue (3 days after non-freezing cold injury versus within 1 day after injury).…”

“…Notably, it was demonstrated that the opening of tight junctions occurred at a later time point than the leakage of Evans blue (3 days after non-freezing cold injury versus within 1 day after injury). It suggested that at the acute phase after cold injury, the breakdown of the blood-nerve barrier might due to other factors besides the changes of tight junctions ( Li et al, 2015 ). Similar as rats underwent crush and transection injuries, rats received intraneurial toxic ricin injection displayed extravasated fluorescein isothiocyanate labeled dextran (FITC-dextran) in the endoneurial and epineurial spaces after an intravascular injection of a 4,000 molecular weight FITC-dextran ( Bouldin et al, 1991 ).…”

The association between high-sensitivity C-reactive protein at admission and progressive motor deficits in patients with penetrating artery infarctions

“…The incidence of PMD ranges from 13 to 38% in patients with PAI [5–8]. Several reports have shown that PMD is also associated with poor prognosis of PAI [9–11]. Although several biomarkers [4, 12] have been identified in previous studies, PMD remains insidious and largely unpredictable in clinical practice.…”

Potential Protective Effect of Vitamin C on Qunalphos-Induced Cardiac Toxicity: Histological and Tissue Biomarker Assay

“…We also showed that in the QP group, there were pleomorphic myelinated nerve cells with damaged myelin and unmyelinated nerve cells. Endoneurial edema is generated by the blood-nerve barrier and the capillary endothelial cell layer, which increases capillary permeability and local pressure gradients, potentially resulting in cellular hypoxia [ 40 ].…”