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Biomedical subjects

N R West

Publications and source records attributed to N R West.

17 recordsLinked to original sources
PubMed2001

Support of axonal regrowth by endogenous mechanisms following spinal cord injury in adult rats.

Because of its non-invasive nature and ease of regulation, a closely monitored cryogenic method of tissue injury was used to create a degree of spinal cord injury within which there would be an extended regrowth of axons. The parameters of cooling used in the present study resulted in an injury length of 1 cm through which 3 mm of measured axonal regrowth and 8 mm of observed regrowth occurred over a 56-day period in the ascending fibers of the dorsal column of the mature rat. This was associated with the development of a cellular matrix consisting of macrophages, macroglia and Schwann cells which gradually expands within the injured area initially dominated by macrophages. It is the authors' impression that the presence of a substantial microglial component within the macrophage population may be a significant factor in the success of the axonal regrowth. Under this influence and that of the invading axons, the astrocyte, which provides the immediate cell support to the growing axon, can be maintained in a functional state that is supportive and not obstructive to the axon, presumably through the recruitment of astrocyte precursors from an indigenous stem cell population. These tissue changes indicate that adult mammalian spinal cord tissue does have the capacity to develop on its own a matrix capable of supporting the regrowth of axons.

Animals↗
PubMed1999

Preservation of synapses on principal cells of the central nucleus of the inferior colliculus with aging in the CBA mouse.

The light and electron microscopic features of principal neurons of the central nucleus of the inferior colliculus were quantitated in the CBA mouse. Three age groups of mice were examined, including young (3 months), middle-aged (8 months) and old (25 months). No changes were noted in the size of the principal neurons over the age range examined. At the ultrastructural level, synapses on the somata of the principal neurons showed no change in the number or type of synapses, the length of synaptic apposition nor the size of synaptic terminal area. These results are in contrast with the moderately severe synapse loss which we previously reported in the C57BL/6 mouse strain, a strain which has a genetic deficit producing progressive sensorineural hearing loss starting in young adulthood (Kazee et al., 1995). In contrast, hearing is quite well-preserved across the lifespan in the CBA mouse strain, making this a useful animal to study the intrinsic effects of aging in the auditory system versus the effects of sensorineural hearing loss. The preservation of synapses on principal neurons in this strain suggests that synaptic loss is not an inevitable event in aging, but may be related to the preservation of peripheral auditory function and input to the neurons.

Aging↗
PubMed1995

Cryogenic spinal cord injury induces astrocytic gene expression of insulin-like growth factor I and insulin-like growth factor binding protein 2 during myelin regeneration.

To study injury-induced astrocytic responses associated with regrowth of axons and regeneration of myelin, the method of Collins and colleagues was used to make focal cryogenic lesions in spinal cords of adult rats (Collins et al.: J Neuropathol Exp Neurol 45: 742-757, 1986). The duration of cryogenic injury (CI), the size of the cryode, and its temperature were chosen to destroy all myelin sheaths and axons without producing cavities or hemorrhages. Messenger RNA and peptide distributions of insulin-like growth factor I (IGF-I), IGF-I receptor (IGFR-I), IGF binding protein 2 (IGFBP-2), glial fibrillary acidic protein (GFAP), and myelin basic protein (MBP) were studied 3-56 days after CI by in situ hybridization and immunocytochemistry. At 3 days, vimentin-positive, GFAP-negative astrocyte-like cells in the lesion expressed IGF-I mRNA and peptide and 7 days after CI, both were expressed by typical GFAP-positive, hypertrophic astrocytes, many of which also were vimentin-positive. Levels of IGF-I, IGFBP-2, and GFAP mRNA and peptide were higher in lesion astrocytes after 14 days. They attained maximum levels at 21-28 days before declining to near control levels at 56 days. Decreasing relative levels of oligodendroglial MBP mRNA were found in and around lesions 7-14 days after CI; subsequently, rising levels accompanied remyelination. At 28 and 56 days after CI, some transferrin-positive, oligodendroglia-like cells also were immunostained by anti-IGFR-I. Our findings suggest that early astrocytic production of IGF-I and IGFBP-2 may be involved in the myelin regeneration which occurs in this model of spinal cord injury.

Animals↗
PubMed1991

Relationship of Wallerian degeneration to regrowing axons.

Because Wallerian degeneration constitutes a highly significant and unavoidable position in the sequence of nervous system regeneration we have extended our observations regarding this process as it occurs in our cryogenic model of spinal cord injury in the rat. In previous studies we have observed essentially no growth into the Wallerian zone despite a significant amount of axonal regrowth through the injured region. In the present study we have examined by electron microscopy the Wallerian degeneration and its interface with the axons from the injured region. In the Wallerian region our observations have not only confirmed those of many previous investigators but have suggested an orderly sequence of changes during the first 60 days post-injury, beginning with relative tissue preservation followed by depletion of degenerating axoplasm, extracellular deposition of myelin and the development of a cellular reaction. Associated with the cellular reaction is the development of large astrocytic cells which can be found adjacent to unmyelinated and thinly myelinated axons. With this limited evidence of support for axonal growth in the Wallerian zone it is suggested that further expansion of this cellular matrix should provide significant support to regrowing axons.

Animals↗
PubMed1989

Glial activity during axonal regrowth following cryogenic injury of rat spinal cord.

The cryogenic model of spinal cord injury is associated with regrowth of axons through a zone of injury which is composed of a complex matrix of intact blood vessels, cells and extracellular materials. We have used this, therefore, as a means for studying the relationship between these cellular components, particularly the astrocytes, and the regrowing axons. For the time period of 60 days following injury we have found that, from an undifferentiated group of cells which appears early, there develops a population of astrocytes which is associated with the restoration of neural structure, including the return of axons, to the damaged area. We interpret these associations to be supportive through direct axonal interactions and indirect environmental contributions.

Animals↗
PubMed1989

Prospects for axonal regrowth in spinal cord injury.

Some of the evidence relating to the possible cellular relationships in regenerating mammalian central nervous tissue is reviewed. From this review it is suggested that data do exist which reveal a potential for regeneration based upon the basic properties and behavior of axons and glial cells. Models of tissue injury which optimize these intrinsic capabilities may generate significant information about the regenerative possibilities of central nervous tissue.

Animals↗
PubMed1989

Cellular changes during repair of a cryogenic spinal cord injury in the rat: an electron microscopic study.

Cryogenic injury of adult, rat spinal cord was produced under controlled non-invasive conditions to study repair and regeneration in adult, mammalian central nervous tissue in which tissue continuity and integrity are relatively preserved. Under these experimental conditions axons and myelin are destroyed, a matrix of glial cells is preserved, and regrowth of axons is apparent. Electron microscopic studies at 7, 15, 30 and 60 days post-injury demonstrate axonal structures indicative of regrowth, astrocytic structures which appear to provide support to both matrix and axons and myelination of axons by both oligodendrocytes and Schwann cells. These cellular events restore much of the normal structure within the injured area up to its junction with the Wallerian zone. In this junctional zone morphologic evidence may indicate continuing cellular activity, even at 60 days, in axons, astrocytes and myelinating cells. These studies suggest that under ideal conditions damaged axons may be capable of regeneration within the adult mammalian central nervous system and that this model provides an opportunity to define some of the mechanisms.

Animals↗
PubMed1986

The histopathology of freezing injury to the rat spinal cord. A light microscope study. I. Early degenerative changes.

In an effort to develop a method of tissue injury which would provide a model for the study of axonal regrowth in adult mammalian central nervous system (CNS), we have analyzed the effects of freezing in the dorsal columns of more than 200 rat spinal cords. The effects of temperature and time of exposure upon the size, shape, distribution and histologic characteristics of the lesion have been assessed during the first seven days following the injury. The upper threshold for injury occurs at -3 degrees C for 15 minutes. Between -3 degrees C and -12 degrees C the tissue changes vary in extent and characteristics. Selective damage to axons and myelin occurs with sparing of the supportive cells followed by proliferation of a cellular matrix. At seven days, the lesions produced by -8 degrees C for 15 to 60 minutes have neither axons nor myelin sheaths and consist of a dense cellular matrix of macrophages and presumed glial cells. With these tissue characteristics, and the preservation of tissue continuity without obstructive barriers, this model would appear to be potentially suitable for the study of axonal regrowth potential in mammalian CNS.

Animals↗
PubMed1986

The histopathology of freezing injury to the rat spinal cord. A light and electron microscope study. II. Repair and regeneration.

We utilized a recently developed model of spinal cord injury in which freezing of the rat dorsal column produced axonal injury with sparing and proliferation of the supporting tissue. We examined the progress of the reparative and regenerative processes for 15, 30 and 60 days after the injury. In transverse and sagittal sections at the proximal middle, and distal injury zone and at the zone of Wallerian degeneration we have demonstrated an apparent outgrowth of axons which makes its appearance between 15 and 30 days following injury and increases in amount between 30 and 60 days. The myelination of these fibers is bimodal with Schwann cells predominating in the subpial region, and oligodendrocytes in the deeper regions. Growth into the Wallerian zone is significantly less but does occur at 30 days increasing only slightly at 60 days despite extensive clearing of the breakdown products. We believe that the conditions created by this method of injury provide a suitable model for the study of repair and regeneration of mammalian central nervous tissue.

Animals↗
PubMed1981

Alveolar function following surfactant deactivation.

In vivo cinemicroscopic studies of subpleural alveoli were conducted in dogs for 4 h after pulmonary lavage with 5% Tween 20 and after lavage with normal saline. Saline-lavaged alveoli showed little change in alveolar size during tidal ventilation, whereas Tween lavage resulted both in alveolar recruitment and marked variation in alveolar size from end expiration to peak inspiration, with total collapse frequently occurring by end expiration. Following Tween, alveolar stability decreased, but alveolar capillary perfusion increased. Marked recovery of stability by 4 h was noted in most alveoli. Wilhelmy balance studies on lung extracts showed a decrease in surfactant function 30 min after Tween and a partial recovery of surfactant activity after 4 h. This study provides in vivo evidence that normal surfactant function is critical to alveolar stability and that alveolar stability is markedly restored 4 h after acute deactivation or displacement by Tween. Surfactant deactivation and loss of alveolar stability are associated with increased alveolar capillary perfusion creating significant ventilation-perfusion ratio abnormalities.

Animals↗
PubMed1975

Absorption, distribution and excretion of trifluoperazine in rats.

In rats receiving a low oral dose (0.35 mg/kg p.o.) of trifluoperazine (TFP), a potent neuroleptic phenothiazine, the parent drug distribution was separate from that of its metabolite trifluoperazine sulfoxide (TFP-SO). This was not seen after intraperitoneal administration (i.p.) of the same or high dose (5mg/kg). TFP-SO was not detected in the brain, wheras TFP was significantly associated with microsomes when its brain level was highest. Absorption, distribution, metabolism, and dose dependent excretion procedded rapidly with 97% of a dose recovered 24 hr after p.o. treatment, only 6% in the urine and the remainder in feces with 87% of this metabolized to compounds other than TFP-SO. TFP and its metabolites arrived in feces via two pathways, largely the bile plus another route. The excretion pattern was unchanges with other drugs or after treatment for 3 wk, although excretion differed on the first day after i.p. and p.o. administration.

Animals↗