Role of the Blood-Nerve Barrier in Experimental Nerve Edema

Abstract

Nerve edema is a common response to the nerve injury seen in many peripheral neuropathies and is an important component of Wallerian degeneration. However, independent pathologic effects of nerve edema that aggravate or induce nerve injury extend the role of edema beyond that of an epiphenomenon of injury. New insights into the mechanism and impact of nerve edema come largely from animal models. In the following review, we discuss the cause and consequences of nerve edema with particular reference to endoneurial fluid pressure and its relevance to the nerve microenvironment. Experimental models of nerve edema include conditions with increased vascular permeability such as lead poisoning, experimental allergic neuritis, and murine globoid leukodystrophy. Increased perineurial permeability induced by local anesthetics and neurolytic drugs can also induce nerve edema sufficient to increase endoneurial fluid pressure. Both perineurial and vascular permeability are increased after damage induced by crush, freeze, or laser injury. One of the most important forms of nerve edema is induced by external compression; the significance of this change is that edema has local compressive effects that persist after the external pressure has been relaxed. Nerve edema and increased endoneurial fluid pressure also occur in conditions in which vascular permeability appears to be unchanged such as experimental diabetic neuropathy and in hexachlorophene intoxication. In both of these conditions, reduced nerve blood flow has been demonstrated in rats and is viewed as a consequence of increased endoneurial fluid pressure. Whatever its mechanism, endoneurial edema has important structural and functional consequences for nerve fibers. A clear understanding of the underlying pathology ofthe nerve microenvironment may provide useful insights into treatment ofclinical neuropathies.

Characterization of polyol pathway in schwann cells isolated from adult rat sciatic nerves

“…As sorbitol is one of the osmolytes that maintain renal homeostasis, an osmoregulatory role of AR was indicated in the kidney (Burg, 1995). It should be noted that the endoneurial fluid electrolytes were reported to fluctuate in accord once with increases in flux of the polyol pathway (Mizisin et al, 1988(Mizisin et al, , 1990. In this context, it is tempting to suggest that sorbitol in Schwann cells may also act as an osmolyte to balance the alterations in endoneurial fluid electrolyte levels in the peripheral nerves of diabetic patients.…”

Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States

“…However, the effects of proinflammatory cytokines, NO, and ROS extend beyond pathogen killing, because these fibroblastderived substances can also directly increase nerve excitability (160,288,291), damage myelin (202,249,259,283), and/or alter the blood-nerve barrier (83,315). This latter effect leads to edema and infiltration of immune cells, antibodies, and other immune products (198).…”

Concept of acute neuropathic pain. The role of nervi nervorum in the distinction between acute nociceptive and neuropathic pain

“…The activation of nervi nervorum nervous terminations was implied in peripheral nervous trunk referred pain 25,46,57,58 . Bove and Light 59 have observed that nervi nervourm fibers were arranged in the neural space to respond to induced stimuli during nervous injury such as mechanical compression and tension and are positioned to react to changes of the medium were nervous damages occur, such as those caused by increased subperineural pressure and environmental concentrations of histamine and bradikinin 60,61 . Nervi nervorum and nervi vasorum are vulnerable to nervous tissue injuries resulting from friction and chronic compressive syndromes 56 .…”