Aggravated reperfusion injury in STZ‐diabetic nerve

Abstract

The streptozocin (STZ)-diabetic nerve manifests increased morphological susceptibility to a superimposed acute ischemic injury, and reperfusion injury exaggerates ischemic nerve pathology. To determine whether STZ-diabetic nerves are susceptible to reperfusion, we evaluated the pathological consequences after 2.5 hours of ischemia followed by 3 and 24 hours of reperfusion in a 20-week STZ-diabetic rat sciatic nerve. After 3 hours of reperfusion, endoneurial edema developed in diabetic nerves, whereas non-diabetic controls showed mild or no edema. Morphometric analysis of endoneurial edema, quantified by the total transverse fascicular area and the point-count score of endoneurial structureless space, confirmed significantly more reperfusion-induced edema at thigh and knee levels in diabetic nerves than in controls. Reperfusion caused a significant increase in the number of endoneurial mast cells at the thigh level in diabetic nerves. After 24 hours of reperfusion, there were striking morphological anomalies of myelinated nerve fibers in diabetic nerves, without any observable changes in control nerves. In conclusion, we have demonstrated that STZ-diabetes exacerbates the morphological change to reperfusion. Diabetes therefore renders the microvasculature more vulnerable to the deleterious effects of ischemia/reperfusion.

Decreased peripheral nerve damage after ischemia–reperfusion injury in mice lacking TNF-alpha

“…Previous studies have demonstrated that ischemia to nerve can cause fiber degeneration, and reperfusion following ischemia causes additional fiber degeneration, mediated by an inflammatory response and oxidative stress [2,3]. The current finding of less edema and fiber degeneration in sciatic but not in tibial nerve is consonant with our previous studies that demonstrate that neuroprotection, whether with hypothermia or antioxidants, occurs when the ischemic insult is moderate (sciatic nerve) but fails when the insult is extreme [11,12,15,16].…”

“…Reperfusion following ischemia (IR) results in additional fiber degeneration, and mechanisms of reperfusion injury have been postulated to be due to the additional insult of inflammatory response [2] and oxidative injury [3]. The pro-inflammatory cytokines, especially tumor necrosis factor-alpha (TNF-α), is a major component of the inflammatory response following IR injury and is rapidly upregulated from mRNA level to protein level [4][5][6][7].…”

Enhanced inflammatory response via activation of NF-κB in acute experimental diabetic neuropathy subjected to ischemia–reperfusion injury

“…These alterations are known to be exaggerated in diabetic neuropathy [15]. In our previous study, we demonstrated that reperfusion following ischemia results in excessive axonal degeneration [3] and apoptosis of SC [6,7] in 1-month and 4-month diabetic peripheral nerve when compared with normal nerves subjected to the identical insult.…”

Ischemia–reperfusion injury of peripheral nerve in experimental diabetic neuropathy

“…Reperfusion amplifies physiological and pathological abnormalities in ischemic nerves of normal rat [10] and exaggerates the ischemia pathology in a 20-week STZ-diabetic rat sciatic nerve after 2.5 h of ischemia followed by 3 and 24 h of reperfusion [11].…”