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J McGraw

Publications and source records attributed to J McGraw.

12 recordsLinked to original sources
PubMed2005

Regulation of neuronal and glial galectin-1 expression by peripheral and central axotomy of rat primary afferent neurons.

Galectin-1 (Gal1) is an endogenously-expressed protein important for the embryonic development of the full complement of primary sensory neurons and their synaptic connections in the spinal cord. Gal1 also promotes axonal regeneration following peripheral nerve injury, but the regulation of Gal1 by axotomy in primary afferent neurons has not yet been examined. Here, we show by immunohistochemistry and in situ hybridization that Gal1 expression is differentially regulated by peripheral nerve injury and by dorsal rhizotomy. Following peripheral nerve injury, the proportion of Gal1-positive DRG neurons was increased. An increase in the proportion of large-diameter DRG neurons immunopositive for Gal1 was paralleled by an increase in the depth of immunoreactivity in the dorsal horn, where Gal1-positive terminals are normally restricted to laminae I and II. Dorsal rhizotomy did not affect the proportions of neurons containing Gal1 mRNA or protein, but did deplete the ipsilateral dorsal horn of Gal1 immunoreactivity, indicating that it is transported centrally by dorsal root axons. Dorsal rhizotomy also resulted in an increase in Gal1 mRNA the nerve peripheral to the PNS-CNS interface (likely within Schwann cells and/or macrophages), and to a lesser extent within deafferented spinal cord regions undergoing Wallerian degeneration. This latter increase was notable in the dorsal columns and along the prior trajectories of myelinated afferents into the deeper dorsal horn. These results show that neuronal and glial expressions of Gal1 are tightly correlated with regenerative success. Thus, the differential expression pattern of Gal1 following peripheral axotomy and dorsal rhizotomy suggests that endogenous Gal1 may be a factor important to the regenerative response of injured axons.

Analysis of Variance↗
PubMed2004

Altered primary afferent anatomy and reduced thermal sensitivity in mice lacking galectin-1.

The transmission of nociceptive information occurs along non-myelinated, or thinly myelinated, primary afferent axons. These axons are generally classified as peptidergic (CGRP-expressing) or non-peptidergic (IB4-binding), although there is a sub-population that is both CGRP-positive and IB4-binding. During neuronal development and following injury, trophic factors and their respective receptors regulate their survival and repair. Recent reports also show that the carbohydrate-binding protein galectin-1 (Gal1), which is expressed by nociceptive primary afferent neurons during development and into adulthood, is involved in axonal pathfinding and regeneration. Here we characterize anatomical differences in dorsal root ganglia (DRG) of Gal1 homozygous null mutant mice (Gal1(-/-)), as well as behavioural differences in tests of nociception. Gal1(-/-) mice have a significantly reduced proportion of IB4-binding DRG neurons, an increased proportion of NF200-immunoreactive DRG neurons, increased depth of central terminals of IB4-binding and CGRP-immunoreactive axons in the dorsal horn, and a reduced number of Fos-positive second order neurons following thermal (cold or hot) stimulation. While there is no difference in the total number of axons in the dorsal root of Gal1(-/-) mice, there are an increased number of myelinated axons, suggesting that in the absence of Gal1, neurons that are normally destined to become IB4-binding instead become NF200-expressing. In addition, mice lacking Gal1 have a decreased sensitivity to noxious thermal stimuli. We conclude that Gal1 is involved in nociceptive neuronal development and that the lack of this protein results in anatomical and functional deficits in adulthood.

Afferent Pathways↗
PubMed2004

Galectin-1 expression correlates with the regenerative potential of rubrospinal and spinal motoneurons.

Axotomized spinal motoneurons are able to regenerate to their peripheral targets, whereas injured rubrospinal neurons that lie completely within the CNS fail to regenerate. The differing cell body reactions to axotomy of these two neuronal populations have been implicated in their disparate regenerative ability. Recently, the lectin galectin-1 has been shown to be involved in both spinal motoneurons and primary afferent regeneration. Using in situ hybridization, we compared the endogenous galectin-1 mRNA expression in spinal motoneurons and rubrospinal neurons after axotomy. We found that 7 and 14 days after axotomy, galectin-1 mRNA increased in spinal motoneurons but decreased in rubrospinal neurons. Infusion of the brain-derived neurotrophic factor into the vicinity of the injured rubrospinal nucleus, which we have previously shown to increase the regenerative capacity of rubrospinal neurons, significantly increased galectin-1 mRNA compared with uninjured control levels. Thus, the expression of galectin-1 in neurons correlates with the regenerative propensity.

Analysis of Variance↗
PubMed2004

Galectin-1 in regenerating motoneurons.

The exogenous application of recombinant galectin-1 has recently been shown to promote the rate of peripheral nerve regeneration. Endogenous neuronal galectin-1 expression has recently been demonstrated to increase after axotomy. Here we demonstrate a significant increase in the endogenous neuronal expression of galectin-1 mRNA in facial motoneurons after either a nerve resection or crush injury in mice. This increase in galectin-1 expression was due in part to the loss of target-derived factor(s) as indicated by both the return of galectin-1 expression to control levels following target re-innervation and the increase in galectin-1 expression after blockade of axonal transport by an interneuronal colchicine injection. Furthermore, interneuronal injections of glial-derived neurotrophic factor into the uninjured nerve also increased galectin-1 mRNA expression within facial motoneurons suggesting that positive signals may also be involved in the regulation of galectin-1 expression. Galectin-1 null mutant mice showed an attenuated rate of functional recovery of whisking movement after a facial nerve crush.

Animals↗
PubMed2002

Brain-derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant.

Previous experiments from our laboratory have shown that application of brain-derived neurotrophic factor (BDNF) to the red nucleus or the motor cortex stimulates an increase in the expression of regeneration-associated genes in rubrospinal and corticospinal neurons. Furthermore, we have previously shown that BDNF application stimulates regeneration of rubrospinal axons into a peripheral graft after a thoracic injury. The current study investigates whether application of BDNF to the motor cortex will facilitate regeneration of corticospinal neurons into a peripheral nerve graft placed into the thoracic spinal cord. In adult Sprague Dawley rats, the dorsal columns and the corticospinal tract between T9 and T10 were ablated by suction, and a 5-mm-long segment of predegenerated tibial nerve was autograft implanted into the lesion. With an osmotic pump, BDNF was infused directly into the parenchyma of the motor cortex for 14 days. Growth of the corticospinal tract into the nerve graft was then evaluated by transport of an anterograde tracer. Anterogradely labeled corticospinal fibers were not observed in the peripheral nerve graft in animals treated with saline or BDNF. Serotinergic and noradrenergic fibers, as well as peripheral sensory afferents, were observed to penetrate the graft, indicating the viability of the peripheral nerve graft as a permissive growth substrate for these specific fiber types. Although treatment of the corticospinal fibers with BDNF failed to produce regeneration into the graft, there was a distinct increase in the number of axonal sprouts rostral to the injury site. This indicates that treatment of corticospinal neurons with neurotrophins, e.g., BDNF, can be used to enhance sprouting of corticospinal axons within the spinal cord. Whether such sprouting leads to functional recovery after spinal cord injury is currently under investigation.

Animals↗
PubMed2001

Modulating astrogliosis after neurotrauma.

Traumatic injury to the adult central nervous system (CNS) results in a rapid response from resident astrocytes, a process often referred to as reactive astrogliosis or glial scarring. The robust formation of the glial scar and its associated extracellular matrix (ECM) molecules have been suggested to interfere with any subsequent neural repair or CNS axonal regeneration. A series of recent in vivo experiments has demonstrated a distinct inhibitory influence of the glial scar on axonal regeneration. Here we review several experimental strategies designed to elucidate the roles of astrocytes and their associated ECM molecules after CNS damage, including astrocyte ablation techniques, transgenic approaches, and alterations in the deposition of the ECM. In the short term, mediators that modulate the inflammatory mechanisms responsible for eliciting astrogliotic scarring hold strong potential for establishing a favorable environment for neuronal repair. In the future, the conditional (inducible) genetic manipulation of astrocytes holds promise for further increasing our understanding of the functional biology of astrocytes as well as opening new therapeutic windows. Nevertheless, it is most likely that, to obtain long distance axonal regeneration within the injured adult CNS, a combinatorial approach involving different repair strategies, including but not limited to astrogliosis modulation, will be required.

Animals↗
PubMed1997

In vivo immunological suppression of spinal cord myelin development.

The onset of myelination in the embryonic chick spinal cord begins on embryonic day (E) 12 or E13 of the 21 day in ovo developmental period. This event coincides with a loss of functional axonal regeneration following complete transection of the thoracic spinal cord. In this study, we have characterised an immunological method for delaying the developmental onset of myelination in vivo until later stages of development (developmental myelin-suppression). A single injection of heterologous or homologous serum complement proteins plus myelin-specific, complement-binding antibodies into the spinal cord prior to E13 delayed the onset of myelination until E17. The state of spinal cord myelin was assessed with immunohistochemical, histological and ultrastructural techniques. Northern blot analysis indicated that myelin basic protein mRNA was not down-regulated in myelin-suppressed spinal cords, which suggests that oligodendrocytes survived developmental myelin-suppression. Glial fibrillary acidic protein immunostaining of normal and treated tissue indicated that myelin-suppression did not alter the resident astrocyte population of the spinal cord or elicit astrogliosis. Immunostaining with microtubule-associated protein-2 and thionine staining of normal and myelin-suppressed tissue further indicated that the neuronal architecture was unaffected by the immunological protocol.

Animals↗
PubMed1995

Axonal regeneration and physiological activity following transection and immunological disruption of myelin within the hatchling chick spinal cord.

Transections of the chicken spinal cord after the developmental onset of myelination at embryonic day (E) 13 results in little or no functional regeneration. However, intraspinal injection of serum complement proteins with complement-binding GalC or 04 antibodies between E9-E12 results in a delay of the onset of myelination until E17. A subsequent transection of the spinal cord as late as E15 (i.e., during the normal restrictive period for repair) results in neuroanatomical regeneration and functional recovery. Utilizing a similar immunological protocol, we evoked a transient alteration of myelin structure in the posthatching (P) chicken spinal cord, characterized by widespread "unravelling" of myelin sheaths and a loss of MBP immunoreactivity (myelin disruption). Myelin repair began within 7 d of cessation of the myelin disruption protocol. Long term disruption of thoracic spinal cord myelin was initiated after a P2-P10 thoracic transection and maintained for > 14 d by intra-spinal infusion of serum complement proteins plus complement-binding GalC or 04 antibodies. Fourteen to 28 d later, retrograde tract tracing experiments, including double-labeling protocols, indicated that approximately 6-19% of the brainstem-spinal projections had regenerated across the transection site to lumbar levels. Even though voluntary locomotion was not observed after recovery, focal electrical stimulation of identified brainstem locomotor regions evoked peripheral nerve activity in paralyzed preparations, as well as leg muscle activity patterns typical of stepping in unparalyzed animals. This indicated that a transient alteration of myelin structure in the injured adult avian spinal cord facilitated brainstem-spinal axonal regrowth resulting in functional synaptogenesis with target neurons.

Animals↗
PubMed1991

Two cases of tension pneumopericardium following blunt chest injury.

Tension pneumopericardium is uncommon in blunt trauma, and only rare survivors have been reported. We report two patients who survived tension pneumopericardium following blunt trauma. Both patients experienced signs and symptoms of cardiac tamponade that were corrected by insertion of a subxyphoid pericardial tube. Both survived all injuries and returned to normal activities with normal neurologic function.

Accidents, Traffic↗
PubMed1974

In vitro and in vivo effects of endotoxin on mouse peritoneal cells.

The in vitro effect of endotoxin (LPS) on unfractionated mouse peritoneal cells and cells fractionated into glass adherent and nonadherent populations was studied. LPS caused blast transformation and deoxyribonucleic acid synthesis in the nonadherent, nonphagocytic cells. There was no evidence of a mitogenic effect on macrophages. Instead, a cytotoxic effect was noted. When incubated with unfractionated peritoneal cells, LPS was still cytotoxic for macrophages, but the mitogenic effect for nonadherent cells was decreased or ablated. The intraperitoneal administration of LPS to mice resulted in an acute inflammatory response with a transient depletion of mononuclear cells. There was no stimulation of division of macrophages. Data were obtained which indicated that local cell division is an important factor in the normal turnover of peritoneal macrophages.

Animals↗