Endogenous TrkB Ligands Suppress Functional Mechanosensory Plasticity in the Deafferented Spinal Cord

Ramer, Leanne M.; McPhail, Lowell T.; Borisoff, Jaimie; Soril, Lesley; Kaan, Timothy K. Y.; Lee, Jae H.T.; Saunders, James W. T.; Hwi, Lucy P.-R.; Ramer, Matt S.

doi:10.1523/jneurosci.0491-07.2007

Cited by 41 publications

(31 citation statements)

References 74 publications

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“…Finally, some neurotrophins may suppress sprouting. Ramer et al 32 found that endogenous TrkB ligands suppress sprouting and mechanosensory recovery in rats after dorsal root injuries.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial

Yang

et al. 2011

Spinal Cord

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Study design: Lithium has attracted much attention as a neuroregenerative agent for spinal cord injury in animal models. We hypothesized that the lithium can be beneficial to patients with spinal cord injury. The safety and pharmacokinetics of lithium has been studied in our earlier phase I clinical trial, indicating its safety. This is a phase II clinical trial to evaluate its efficacy on chronic spinal cord injury patients. Objectives: The aim of this study was to investigate the efficacy of lithium on chronic spinal cord injury patients. Setting: A major spinal cord injury rehabilitation center in Beijing, China. Methods: Randomized, double-blind, placebo-controlled 6-week parallel treatment arms with lithium carbonate and with placebo. A total of 40 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was titrated or placebo was simulated to maintain the serum lithium level of 0.6-1.2 mmol l À1 for 6 weeks, followed by a 6-month follow-up. The functional outcomes and the neurological classifications, as well as the safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. Results: No significant changes in the functional outcomes and the neurological classifications were found. The only significant differences were in the pain assessments using visual analog scale comparing the lithium and the placebo group. No severe adverse event was documented in the study. Conclusion: The lithium treatment did not change the neurological outcomes of patients with chronic spinal cord injury. It is worth to investigate whether lithium is effective in the treatment of neuropathic pain in chronic spinal cord injury. Sponsorship: China Spinal Cord Injury Network Company Limited.

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“…Finally, some neurotrophins may suppress sprouting. Ramer et al 32 found that endogenous TrkB ligands suppress sprouting and mechanosensory recovery in rats after dorsal root injuries.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial

Yang

et al. 2011

Spinal Cord

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“…Penetration of spinal parenchyma by intrathecallydelivered proteins,using this technique,has been confirmed previously. 12 The six rats (test/NT-3-treated: n ¼ 3; control/untreated: n ¼ 3) were allowed to survive for one week. In the cervical dorsal root rhizotomy model, in which dorsal roots are injured approximately 2 mm from the cord, one week is sufficient for regeneration up to (but in untreated animals, not beyond) the DRTZ; one week's delivery of NT-3 into the intrathecal space has been shown previously to promote regeneration of primary afferent axons into the cord.…”

Section: Methodsmentioning

confidence: 99%

The impact of neurotrophin-3 on the dorsal root transitional zone following injury

et al. 2008

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Study design: Morphological and Stereological assessment of the dorsal root transitional zone (DRTZ) following complete crush injury, using light microscopy (LM) and transmission electron microscopy (TEM). Objectives: To assess the effect of exogenous neurotrophin-3 (NT-3) on the response of glial cells and axons to dorsal root damage. Setting: Department of Anatomy, University College Cork, Ireland and Department of Physiology, UMDS, University of London, UK. Methods: Cervical roots (C6-8) from rats which had undergone dorsal root crush axotomy 1 week earlier, in the presence (n ¼ 3) and absence (n ¼ 3) of NT-3, were processed for LM and TEM. Results: Unmyelinated axon number and size was greater in the DRTZ proximal (Central Nervous System; CNS) and distal (Peripheral Nervous System; PNS) compartments of NT-3-treated tissue. NT-3 was associated with a reduced astrocytic response, an increase in the proportion of oligodendrocytic tissue and a possible inhibition or delay of microglial activation. Disrupted-myelin volume in the DRTZ PNS and CNS compartments of treated tissue was lower, than in control tissue. In the PNS compartment, NT-3 treatment increased phagocyte and blood vessel numbers. It decreased myelinating activity, as sheath thickness was significantly lower and may also account for the noted lower Schwann cell and organelle volume in the test group. Conclusions: Our observations suggest that NT-3 interacts with non-neuronal tissue to facilitate the regenerative effort of damaged axons. This may be as a consequence of a direct action or indirectly mediated by modulation of non-neuronal responses to injury.

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“…Animals were killed with an overdose of chloral hydrate (1 g/kg intraperitoneally; Sigma-Aldrich Canada Ltd., Oakville, Ontario, Canada), and tissue was processed by standard methods (Ramer et al, 2007). Cords were cut transversely (16 m) and thaw-mounted onto glass slides or were cut parasagittally (40 m) for floating-section immunohistochemistry.…”

Section: Antibody Characterization Immunohistochemistry and Imagingmentioning

confidence: 99%

Anatomical and functional characterization of neuropil in the gracile fasciculus

Ramer¹

2008

J of Comparative Neurology

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A fundamental organizational principle of the central nervous system is that gray matter is the province of neuronal somata, white matter their processes. However, the rat and primate dorsal columns (archetypal spinal "white matter" tracts) are actually of intermediate character, insofar as they contain a surprisingly prominent neuropil of unknown function. Here I report on the morphology, inputs, projections, and functional properties of these neurons. Small fusiform and larger lentiform neurons are most abundant in the gracile fasciculus of the cervical and lumbar enlargements and are absent from the cuneate fasciculus and corticospinal tract. Many have dendrites that run along the dorsal pia, and, although in transverse sections these neurons appear isolated from the gray matter, they are also connected to area X by varicose and sometimes loosely fasciculated dendrites. These neurons receive neurochemically diverse, compartmentalized synaptic inputs (primary afferent, intrinsic and descending), half express the substance P receptor, and some project supraspinally. Unlike substantia gelatinosa neurons, they do not express protein kinase C gamma. Functionally, they have small receptive fields, which are somatotopically appropriate with respect to their anterior-posterior position along the neuraxis. They respond to innocuous and/or noxious mechanical stimulation of the distal extremities, and some are prone to central sensitization or "windup." Morphologically, neurochemically, and functionally, therefore, these cells most closely resemble neurons in laminae III-VI in the dorsal horn. The proximity of their dorsal dendrites to the pia mater may also reflect an ability to integrate internal (e.g., changes in cerebrospinal fluid compostition) and external (e.g., somatic) stimuli.

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Endogenous TrkB Ligands Suppress Functional Mechanosensory Plasticity in the Deafferented Spinal Cord

Cited by 41 publications

References 74 publications

Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial

Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial

The impact of neurotrophin-3 on the dorsal root transitional zone following injury

Anatomical and functional characterization of neuropil in the gracile fasciculus

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