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M P Pender

Publications and source records attributed to M P Pender.

83 records · Page 5Linked to original sources

The pathophysiology of acute experimental allergic encephalomyelitis induced by whole spinal cord in the Lewis rat.

Histological and electrophysiological studies were performed on Lewis rats with acute experimental allergic encephalomyelitis (EAE) induced by inoculation with guinea-pig spinal cord and Freund's adjuvants, in order to determine the cause of the neurological signs. These studies demonstrated demyelination-induced nerve conduction block in the large and also the smaller diameter fibres at the ventral root exit zone (VREZ) of the lumbar spinal cord. The demyelination at the VREZ affected both centrally and peripherally myelinated internodes, but predominantly the former. Studies on the H reflex recorded from a hindfoot muscle indicated normal peripheral nerve motor conduction but interruption of the monosynaptic reflex arc, as would be anticipated from this efferent conduction block and previously reported afferent conduction abnormalities. It is concluded that conduction block in alpha, beta and gamma motor fibres at the VREZ is an important cause of hindlimb weakness in whole spinal cord-induced acute EAE.

Animals↗

Demyelination and neurological signs in experimental allergic encephalomyelitis.

Because of the reported absence of demyelination in some animals with neurological signs of experimental allergic encephalomyelitis (EAE), it has been suggested that these signs are not due to demyelination. The present study demonstrates that there is ample demyelination in the central nervous system (CNS) and peripheral nervous system (PNS) to account for the neurological signs in rats with myelin basic protein (MBP)-induced acute EAE as well as in rats and rabbits with whole-spinal-cord-induced acute EAE. The main reasons for failure to detect demyelination in animals with neurological signs of EAE appear to be inadequate histological techniques and incomplete examination of the nervous system, particularly the PNS and the lumbar, sacral and coccygeal segments of the spinal cord.

Animals↗

Conduction block due to demyelination at the ventral root exit zone in experimental allergic encephalomyelitis.

Histological and electrophysiological studies were performed in Lewis rats with experimental allergic encephalomyelitis (EAE) to determine the cause of the neurological signs. The ventral root exit zone of the spinal cord was shown to be a major site of demyelination and conduction block. It is concluded that demyelination-induced conduction block in this region is an important cause of hindlimb weakness and paralysis in Lewis rats with EAE.

Animals↗

Involvement of the dorsal root ganglion in acute experimental allergic encephalomyelitis in the Lewis rat. A histological and electrophysiological study.

Histological and electrophysiological studies were performed in Lewis rats with acute experimental allergic encephalomyelitis (EAE) in order to determine the extent of dorsal root ganglion (DRG) involvement. Histological studies showed inflammation and demyelination in both the central nervous system (CNS) and peripheral nervous system (PNS). The DRG was the most affected region of the PNS and its involvement increased caudally. Nerve conduction abnormalities were demonstrated in the regions of the lumbar, sacral or coccygeal DRGs in some of the rats with EAE. However, the overall DRG involvement was much less severe, both histologically and functionally, than what we recently found in rabbits with EAE. Conduction through the lumbar dorsal root entry zone was normal. We conclude that lesions of the afferent pathway to the spinal cord do not contribute significantly to the disturbances of hindlimb motor function in Lewis rats with EAE.

Animals↗

Ascending impairment of nociception in rats with experimental allergic encephalomyelitis.

An ascending impairment of tail nociception is a previously undescribed clinical sign of acute experimental allergic encephalomyelitis (EAE) in the rat. It occurs in EAE induced by inoculation with purified central nervous system (CNS) myelin basic protein (MBP) as well as with whole spinal cord. It is invariably present and consists of an absence of the vocalization response to noxious mechanical stimulation of the tail. This impairment of nociception evolves over 1-3 days, simultaneously with the development of tail weakness, and resolves more rapidly than the tail weakness. Light-microscopic, electron-microscopic and electrophysiological studies indicate that it is due to demyelination-induced conduction block in the small diameter myelinated afferent (A delta) fibres in the sacral and coccygeal dorsal root ganglia, dorsal roots and dorsal root entry zones. Unmyelinated fibres appear to be largely spared.

Animals↗

Vulnerability of the dorsal root ganglion in experimental allergic encephalomyelitis.

The dorsal (posterior) root ganglion is a relatively neglected part of the nervous system from the clinical point of view. In recent studies on the pathophysiology of experimental allergic encephalomyelitis (EAE), the main animal model of multiple sclerosis, the DRG of the rabbit was shown to be the site of extensive inflammation and demyelination and of focal conduction block in a high proportion of the large diameter afferents. The resulting severe functional peripheral deafferentation accounts for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. The vulnerability of the DRG is due to a deficient blood-nerve barrier and possibly also to a susceptibility of the branch point of the ganglion neurone to demyelination-induced conduction block. These and other studies in experimental animals suggest that in man the DRG may be a preferential (but neglected) site of focal structural and functional abnormalities in inflammatory and also other neurological diseases.

Action Potentials↗

The pathophysiology of acute experimental allergic encephalomyelitis in the rabbit.

Clinical, histological and electrophysiological studies were performed on rabbits with acute experimental allergic encephalomyelitis (EAE). The clinical features were similar to those previously described, with the notable exception of the new findings of areflexia, respiratory slowing and hypothermia. The histological findings were also similar to those previously reported, with inflammatory demyelinating lesions both in the central and peripheral nervous system, especially the dorsal root ganglia. Electrophysiological studies performed one to nine days after the onset of neurological signs demonstrated conduction block in a high proportion of the large diameter afferents in the lumbosacral and thoracic dorsal root ganglia. Single fibre studies with spike-triggered averaging confirmed the conduction block in the dorsal root ganglia. That the conduction block was due to demyelination was indicated by slowing of conduction in large diameter fibres, normal conduction in unmyelinated fibres and the specific effects of temperature and of the potassium channel blocking agent, 4-aminopyridine. These conduction abnormalities in the peripheral nervous system, focused on the dorsal root ganglia, account for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. Such conduction block is likely to mask the expression of any lesions of the central nervous system that alone could produce similar signs. The implications of these findings for the human demyelinating diseases are discussed.

Afferent Pathways↗

A simple method for high resolution light microscopy of nervous tissue.

A simple method for high resolution light microscopy of nervous tissue is described. Tissue perfused with glutaraldehyde and formaldehyde and postfixed with osmium tetroxide is embedded in HistoResin (LKB Bromma), a new glycol methacrylate based embedding medium, and sectioned (2 microns) on a standard microtome. The method gives excellent preservation of tissue structure, which is far superior to that in paraffin sections and in fact resembles that in epoxy resin-embedded material. It does not, however, require the time, expertise and ultramicrotome needed to cut epoxy resin sections. This technique is particularly useful for assessing demyelination.

Animals↗