Peripheral nervous system demyelination

Raine, C. S., Wisniewski, H. and Prineas, J. An ultrastruc-tural study of experimental demyelination and remyelin-ation. II. Chronic experimental allergic encephalomyelitis in the peripheral nervous system. Lab. Invest. 21 316-327, 1969. 

The histological investigation showed that these OPC did not produce degeneration and demyelinization in hen s spinal cord and peripheral nervous system. 

Oligodendrocytes are present in the CNS as well and wrap around axons to form a myelin sheath. Myelin wraps into concentric layers that spiral around the axon. Gaps in the oligodendrocytes are the nodes of Ranvier, where the membrane maintains contact with extracellular fluid. The nodes serve to propagate the action potential in myelinated axons. Schwann cells perform an analogous function, myelinating axons in the peripheral nervous system. Not all neurons are myelinated, but myelination increases the metabolic efficiency of action potentials. Demyelination of neurons produces deficits in neuronal conduction, as is seen in multiple sclerosis. 

Neurotoxicity Cells of the central nervous system, CNS (brain and spinal cord) and the peripheral nervous system (nerves outside the CNS) Neuronopathies (neuron injury) Axonopathies (axon injury) Demyelination (loss of axon insulation) Interference with neurotransmission... 

CMT diseases are the most frequent hereditary sensory-motor neuropathies. They are distinguished from other types of genetic neuropathies, either purely motor, mainly distal and dysautonomous neuropathies which mainly alter sensory and sympathetic fibers of the peripheral nerves. We only deal here with CMT diseases and among the many genetic causes, those that give rise to primary demyelinating diseases of the peripheral nervous system (PNS). 

In diabetic patients, the incidence of clinically manifested deficits in peripheral nervous system function increases with duration of disease and is approx 50% after 25 yr of disease. The resulting diabetic neuropathies comprise a group of distinct disorders that can affect both somatic and autonomic nerves, the most common of which is symmetric sensory polyneuropathy. Clinical signs of overt human diabetic neuropathy include decreases in nerve conduction velocity and action potential amplitude and in resistance to ischemic conduction failure. These abnormalities may be accompanied by sensory deficits and, in some cases, severe pain. In diabetes of long standing, morphological deterioration is evident, and both nerve fiber loss and segmental demyelination may occur. 

Conduction velocity of an action potential can be increased dramatically by the presence of myelin, a fatty sheath that surrounds the axon and that is interrupted into gaps every millimeter or so at the nodes of Ranvier. Myelin is elaborated by Schwann cells in the peripheral nervous system and by oligodendrocytes in the central nervous system (the biochemistry of myelin will be discussed later in the article). The presence of myelin will dramatically alter the mode and velocity of conduction of the action potential in the axon. As in unmyelinated nerves, the action potential is still transmitted from one section of the axon to another by the presence of local circuit currents. However, the fatty sheath of myelin has poor conduction properties and therefore acts as an insulator. Hence, the local circuit currents jump from one gap to another at the nodes of Ranvier and the rate of conduction is enhanced as local circuit currents travel faster than the action potential itself This process of discontinuous conduction is known as saltatory conduction. Numerous diseases involving myelin deficiency have been described clinically. As one might predict, demyelinating diseases have profound effects on neuronal conduction and on the well-being of the patient. A few of these conditions will be described briefly in the upcoming section on myelin biochemistry. 

Quarles, R. H. Ilyas, A. A. Willison, H. J. Antibodies to glycolipids in demyelinating diseases of the human peripheral nervous system. Chem. Phys. Lipids 1986, 42 235-248. 

Most cells of the immune system are ordinarily kept apart from those of the nervous system by means of the blood-brain barrier. However, allergic encephalomyelitis, in which T cells attack the myelin sheath of brain neurons, can easily be induced in mice.506 A similar autoimmune process is thought to be involved in human multiple sclerosis (see Chapter 30, pp. 1769, 1808, and Fig. 30-9).507,508 High levels of circulating IgM are found in some demyelinating diseases of peripheral neurons.508 In Rasmussen s encephalitis, which causes brain inflammation and epilepsy, serum antibodies attack a glutamate receptor subunit GluR3.509... 

Application of in vitro test methods have become advantageous in specific cases, such as structurally defined compounds and delayed neuropathy, since target cell data and biochemical processes associated in delayed neuropathy are known. Microscopic studies reveal that cases of OPIDN have degeneration of axons followed by demyelination of the nervous system.25,26 Epidemiologic studies have indicated mild impairment of the brainstem, spinal cord, and peripheral nerve functions in Gulf War veterans.27 Such studies are consistent with the spectrum of OPIDN syndrome. The main nerve agents have been shown to inhibit NTE in vitro as well as in vivo. Sarin has been shown to produce delayed neurotoxicity when administered at higher doses in protected hens.25-27... 

Histologically, a diffuse, symmetrical, extensive demyelination is seen. There may be almost complete lack of myelin sheaths in the central nervous system (Jervis 1960) with the exception, in most cases, of some U-fibers and of myelin sheaths within the central grey nuclei and the optic radiation. Demyelination is most marked in the internal capsule and pyramidal tracts spinal roots and peripheral nerves are involved to a lesser degree (Jacobi 1947 Bertrand et al. 1954). There may be partial loss, or in the center of involved regions, complete loss of axis cylinders. In the periphery of demyelinized areas they may be swollen and terminally distended (Hollander and Pilz 1964). The axis cylinders of U-fibers are, in general, well preserved. Small inflammatory lymphocytic infiltrates may be seen perivascularly. 

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