Acute inflammatory demyelination in reperfusion nerve injury

Abstract

We investigated the pathological appearance of acute inflammation and its role in the development of demyelination in reperfused rat sciatic, tibial, and peroneal nerves after a 5-hour period of near-complete ischemia. Polymorphonuclear neutrophil migration was seen early in the endoneurial lesion. After 18 hours of reperfusion, there was maximal intercellular adhesion molecule-1 expression on endoneurial vessels, and polymorphonuclear neutrophil accumulation was then prominent, reaching a peak 24 hours after reperfusion. Endoneurial mononuclear macrophages increased nearly fourfold after 48 to 72 hours of reperfusion. Macrophages were observed invading Schwann cells and myelin lamellae with associated demyelination. Thus, this study provides evidence of macrophage-associated demyelination after reperfusion similar to that seen in inflammatory neuropathies.

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

“…Reperfusion following ischemia results in additional ischemic axonal damage, presumably by enhancing oxidative stress and the inflammatory response with an elevated production of inflammatory mediators and increased adherence and infiltration of inflammatory cells [2,5,14]. These alterations are known to be exaggerated in diabetic neuropathy [15].…”

“…Ischemia, insufficient to cause fiber degeneration in normal nerve, can induce severe fiber degeneration in diabetic nerve [1,2]. Reperfusion following ischemia can further aggravate axonal degeneration [3][4][5] and cause Schwann cell (SC) apoptosis [6,7].…”

“…Reperfusion following ischemia can further aggravate axonal degeneration [3][4][5] and cause Schwann cell (SC) apoptosis [6,7]. The mechanism(s) of aggravation of fiber injury in diabetic neuropathy subjected to ischemia -reperfusion (IR) injury remains unclear, although an inflammatory response and oxidative stress occur during reperfusion and are implicated in the pathogenesis of reperfusion injury in the peripheral nervous system (PNS) [2,8]. Our studies have focused on the hypothesis that there is enhanced inflammatory response in diabetic nerves subjected to IR injury resulting in excessive injury to axons and SC.…”

Rats with chronic post-ischemia pain exhibit an analgesic sensitivity profile similar to human patients with complex regional pain syndrome — type I

“…Three distinct painful conditions can be generated after a 3 h-ischemia/reperfusion injury, including: 1) acute inflammation (2 days post-procedure, sensitive to morphine, dexamethasone and pregabalin) when tissues exhibit oxidative injury (Nagamatsu et al, 1996), and a local production of inflammatory mediators (Nukada et al, 2000); 2) a persistent ischemic condition, which is a direct consequence of the ischemia/reperfusion insult to blood vessels, and is evidenced by poor blood flow (Fitzal et al, 2002); and 3) secondary neuropathic injury due to nerve fiber degeneration as a consequence of the poor blood flow in nerves (Nagamatsu et al, 1996). The latest phase of chronic post-ischemia pain (7 days post-ischemia/reperfusion) is probably a combination of these 3 painful conditions.…”

Effector mechanisms in anti-MAG antibody-mediated and other demyelinating neuropathies

“…In both chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain -Barré syndrome (GBS), they have been described to engulf myelin or axons, following antibody binding or other nerve damage [1,2]. They can also secrete damaging substances such as tumor necrosis factora (TNF-a), oxygen radicals, nitric oxide, or proteases.…”