BCIT Citations Collection | BCIT Institutional Repository

BCIT Citations Collection

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Collection of published works from BCIT researchers, faculty, and instructors.

Deafferentation and neurotrophin-mediated intraspinal sprouting
Axonal plasticity in the adult spinal cord is governed by intrinsic neuronal growth potential and by extracellular cues. The p75 receptor (p75(NTR)) binds growth-promoting neurotrophins (NTs) as well as the common receptor for growth-inhibiting myelin-derived proteins (the Nogo receptor) and so is well situated to gauge the balance of positive and negative influences on axonal plasticity. Using transgenic mice lacking the extracellular NT-binding domain of p75(NTR) (p75-/- mice), we have examined the influence of p75(NTR) on changes in the density of primary afferent (calcitonin gene-related peptide-expressing) and descending monoaminergic (serotonin- and tyrosine hydroxylase-expressing) projections to the dorsal horn after dorsal rhizotomy, with and without concomitant application of exogenous nerve growth factor and NT-3. We found that, in intact p75-/- mice, the axon density of all populations was equal to or less than that in wild-type mice but that rhizotomy-induced intraspinal sprouting was significantly augmented. Monoaminergic axon sprouting was enhanced in both nerve growth factor- and NT-3-treated p75-/- mice compared with similarly treated wild-type mice. Primary afferent sprouting was particularly robust in NT-3-treated p75-/- mice. These in vivo results illustrate the interactions of p75(NTR) with NTs, with their respective tropomyosin-related kinase receptors and with inhibitory myelin-derived molecules. Our findings illustrate the pivotal role of p75(NTR) in spinal axonal plasticity and identify it as a potential therapeutic target for spinal cord injury., Peer-reviewed article, Published. Received 14 August 2004; Revised 7 October 2004; Accepted 25 October 2004.
Detection and classification of sensory information from acute spinal cord recordings
One avenue of research for partial restoration of function following spinal cord injury is the use of neural prostheses, an example of which is functional electrical stimulation (FES) devices for motor functions. Neural prostheses may also be useful for the extraction of sensory information directly from the nervous system. We suggest the spinal cord as a possible site for the detection of peripheral sensory information from neural activity alone. Acute multichannel extracellular recordings were used to extract neural spike activity elicited from peripheral sensations from the spinal cords of rats. To test the recording method and classification potential, eight classes of sensory events were recorded consisting of electrical stimulation of seven locations on rat forepaws, and another class of data during which no stimulus was present. A dual-stage classification scheme using principal component analysis and k-Means clustering was devised to classify the sensory events during single trials. The eight tasks were correctly identified at a mean accuracy of 96%. Thus, we have shown the methodology to detect and classify peripheral sensory information from multichannel recordings of the spinal cord. These methods may be useful, for example, in a closed-loop FES for restoration of hand grasp., Peer-reviewed article, Published. Manuscript received October 24, 2005; revised February 25, 2006.
Dynamic wheelchair seating positions impact cardiovascular function after spinal cord injury
Innovative wheelchairs allow individuals to change position easily for comfort and social situations. While these wheelchairs are beneficial in multiple ways, the effects of position changes on blood pressure might exacerbate hypotension and cerebral hypoperfusion, particularly in those with spinal cord injury (SCI) who can have injury to autonomic nerves that regulate cardiovascular control. Conversely, cardiovascular benefits may be obtained with lowered seating. Here we investigate the effect of moderate changes in wheelchair position on orthostatic cardiovascular and cerebrovascular reflex control.Nineteen individuals with SCI and ten neurologically-intact controls were tested in supine and seated positions (neutral, lowered, and elevated) in the Elevation™ wheelchair. Participants with SCI were stratified into two groups by the severity of injury to cardiovascular autonomic pathways. Beat-to-beat blood pressure, heart rate and middle cerebral artery blood flow velocity (MCAv) were recorded non-invasively.Supine blood pressure and MCAv were reduced in individuals with lesions to autonomic pathways, and declined further with standard seating compared to those with preserved autonomic control. Movement to the elevated position triggered pronounced blood pressure and MCAv falls in those with autonomic lesions, with minimum values significantly reduced compared to the seated and lowered positions. The cumulative duration spent below supine blood pressure was greatest in this group. Lowered seating bolstered blood pressure in those with lesions to autonomic pathways.Integrity of the autonomic nervous system is an important variable that affects cardiovascular responses to orthostatic stress and should be considered when individuals with SCI or autonomic dysfunction are selecting wheelchairs.This work was supported in part by the Heart and Stroke Foundation of British Columbia and the Yukon (V.E.C)., Peer-reviewed article, Published. Received: December 14, 2016 ; Accepted: June 12, 2017 ; Published: June 30, 2017
Endogenous TrkB ligands suppress functional mechanosensory plasticity in the deafferented spinal cord
Dorsal root injury (DRI) disrupts the flow of sensory information to the spinal cord. Although primary afferents do not regenerate to their original targets, spontaneous recovery can, by unknown mechanisms, occur after DRI. Here, we show that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), but not nerve growth factor or neurotrophin-4, are upregulated in the spinal gray matter after DRI. Because endognous BDNF and NT-3 have well established roles in synaptic and axonal plasticity, we hypothesized that they contributed to spontaneous recovery after DRI. We first developed a model of DRI-induced mechanosensory dysfunction: rat C7/8 DRI produced a deficit in low-threshold cutaneous mechanosensation that spontaneously improved within 10 d but did not recover completely. To determine the effects of endogenous BDNF and NT-3, we administered TrkB-Fc or TrkC-Fc fusion proteins throughout the recovery period. To our surprise, TrkB-Fc stimulated complete recovery of mechanosensation by 6 d after DRI. It also stimulated mechanosensory axon sprouting but prevented deafferentation-induced serotonergic sprouting. TrkC-Fc had no effect on low-threshold mechanosensory behavior or axonal plasticity. There was no mechanosensory improvement with single-bolus TrkB-Fc infusions at 10 d after DRI (despite significantly reducing rhizotomy-induced cold pain), indicating that neuromodulatory effects of BDNF did not underlie mechanosensory recovery. Continuous infusion of the pan-neurotrophin antagonist K252a also stimulated behavioral and anatomical plasticity, indicating that these effects of TrkB-Fc treatment occurred independent of signaling by other neurotrophins. These results illustrate a novel, plasticity-suppressing effect of endogenous TrkB ligands on mechanosensation and mechanosensory primary afferent axons after spinal deafferentation., Peer-reviewed article, Published. Received Oct. 2, 2006; revised March 26, 2007; accepted April 20, 2007.