Neurotrophin treatment to promote regeneration after traumatic CNS injury

Kelamangalath, Lakshmi; Smith, George M.

doi:10.1007/s11515-013-1269-8

Cited by 18 publications

(10 citation statements)

References 83 publications

(100 reference statements)

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“…22,30,31 It is now well established that neurotrophins are important mediators of neuronal development, where they modulate dendritic growth and remodeling, membrane receptor trafficking, neurotransmitter release and synapse formation and function. 20,[32][33][34] In our study, neutrophins had a physiological role in the dendritic architecture in the hippocampus. This observation is in line with previous work showing that BDNF regulates dendritic architecture during the early development of hippocampal neurons.…”

Section: Discussionsupporting

confidence: 48%

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

Zhang

Zou

et al. 2015

Human Vaccines & Immunotherapeutics

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y These authors equally contributed to this work.Keywords: dendritic complexity, fractal dimension, neurotrophin, spine, sholl analysis Abbreviations: BCG, Bacillus Calmette-Gu erin; CNS, central nevers system; BDNF, brain derived neurotrophic factor; IGF-1, insulin-like growth factor 1; AMPA, a-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptorDendritic structure is sensitive to changes in the environment during brain development. Accumulating evidence has demonstrated that early immune activation can significantly affect neuronal development. Our study concentrated on the morphological study of neural dendrites and spines in the hippocampal CA1 area using Diolistic labeling with Sholl analysis and fractal analysis. The results revealed that Bacille Calmette-Gu erin (BCG) vaccination enhanced dendritic complexity, as reflected by the increased number of intersections, number of branch points and fractal dimension, and promoted neurite outgrowth. In addition, BCG increased the density and promoted the maturation of dendritic spines. The alterations in dendritic structure and spine morphology were observed at 2 and 4 w, but the differences were more apparent at 4 w than at 2 w. However, no significant difference was observed at 8 w. Furthermore, we observed that BCG increased the expression of hippocampal brain derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1). Hippocampal BDNF/IGF-1 was positively correlated with apical dendritic length, fractal dimension, and spine density. Taken together, we show in this study that neonatal BCG vaccination promotes dendritic development in developing hippocampal CA1 neurons, most likely by increasing the expression of BDNF and IGF-1 in the hippocampus.

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Section: Discussionsupporting

confidence: 48%

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

Zhang

Zou

et al. 2015

Human Vaccines & Immunotherapeutics

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“…As a mechanism of OPN expression related change in the developmental cerebellum, we focused on the BDNF for its role in processes including neurogenesis, synaptogenesis, axogenesis, and myelination [51,52]. Physiologically, OPN promotes the expression of pro-survival genes via nuclear factor kappa-b (NF- K B) [53].…”

Section: Discussionmentioning

confidence: 99%

Effects of Ascorbic Acid on Osteopontin Expression and Axonal Myelination in the Developing Cerebellum of Lead-Exposed Rat Pups

Nam

Seo

Nahm

et al. 2019

IJERPH

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Osteopontin (OPN) is a multi-functional protein that binds to integrin and calcium-binding phosphoprotein. OPN is required for normal neuronal development and its axonal myelination. We studied the combined effect of lead (Pb) and ascorbic acid treatment on OPN expression in the developing cerebellum. We randomly divided pregnant female rats into three groups: control, Pb (lead acetate, 0.3%, drinking water), and Pb plus ascorbic acid (PA; ascorbic acid, 100 mg/kg, oral intubation) groups. The blood level of Pb was significantly increased, while ascorbic acid reduced Pb levels in the dams and pups. At postnatal day (PND) 21, results from Nissl staining and OPN immunohistochemistry demonstrated that OPN was detected in the Purkinje cell layer in the cerebellum. Ascorbic acid treatment mitigated Pb exposure-induced reduction in the number of intact Purkinje cells and OPN immunoreactive Purkinje cells in the cerebellum of pups. In addition, Pb-induced reduction in the number of oligodendrocytes and myelin-associated glycoprotein is associated with the malformation of the myelin sheath. Ascorbic acid provided protection from Pb-induced impairments. Pb-induced structural deficits in the cerebellum resulted in functional deterioration observed during locomotive tests (bar holding test and wire mesh ascending test), while ascorbic acid ameliorated these harmful effects. Present results suggest that the change of OPN is associated with myelination in the developing cerebellum. The results also demonstrated that exposure to Pb is harmful, while ascorbic acid treatment is beneficial.

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“…The failure of axon growth in the adult spinal cord is due to limitation in the intrinsic capacity of the central nervous system (CNS) neurons to regenerate as well as environmental barriers, including the lack of growth support, the presence of inhibitory factors at the lesion area and formation of scar and cavities, which together impede axon growth and connectivity. Strategies that have been used to promote axonal regeneration after SCI at different stages of the injury (Coumans et al, 2001; Jin et al, 2002; Liu et al, 1999; Lorgulescu et al, 2015) include: administration of neurotrophic factors (Elliott Donaghue et al, 2015; Kelamangalath and Smith, 2013), neutralization or blocking inhibitory factors (Brosamle et al, 2000; Fouad et al, 2001; Petrosyan et al, 2013), reducing scar formation (Houle et al, 2006; Yick et al, 2004) and bridging the lesion cavity using cellular transplants (Bonner et al, 2010; David and Aguayo, 1981; Jin et al, 2002; Reier et al, 1986; Santos-Benito and Ramon-Cueto, 2003; Xu et al, 1995b).…”

Section: Introductionmentioning

confidence: 99%

Axonal regeneration of different tracts following transplants of human glial restricted progenitors into the injured spinal cord in rats

2018

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The goal of this study was to compare the efficacy of human glial restricted progenitors (hGRPs) in promoting axonal growth of different tracts. We examined the potential of hGRPs grafted into a cervical (C4) dorsal column lesion to test sensory axons, and into a C4 hemisection to test motor tracts. The hGRPs, thawed from frozen stocks, were suspended in a PureCol matrix and grafted acutely into a C4 dorsal column or hemisection lesion. Control rats received PureCol only. Five weeks after transplantation, all transplanted cells survived in rats with the dorsal column lesion but only about half of the grafts in the hemisection. In the dorsal column lesion group, few sensory axons grew short distances into the lesion site of control animals. The presence of hGRPs transplants enhanced axonal growth significantly farther into the transplants. In the hemisection group, coerulospinal axons extended similarly into both control and transplant groups with no enhancement by the presence of hGRPs. Rubrospinal axons did not grow into the lesion even in the presence of hGRPs. However, reticulospinal and raphespinal axons grew for a significantly longer distance into the transplants. These results demonstrate the differential capacity of axonal growth/regeneration of the motor and sensory tracts based on their intrinsic abilities as well as their response to the modified environment induced by the hGRPs transplants. We conclude that hGRP transplants can modify the injury site for axon growth of sensory and some motor tracts, and suggest they could be combined with other interventions to restore connectivity.

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Neurotrophin treatment to promote regeneration after traumatic CNS injury

Cited by 18 publications

References 83 publications

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

Neonatal vaccination with bacille Calmette-Guérin promotes the dendritic development of hippocampal neurons

Effects of Ascorbic Acid on Osteopontin Expression and Axonal Myelination in the Developing Cerebellum of Lead-Exposed Rat Pups

Axonal regeneration of different tracts following transplants of human glial restricted progenitors into the injured spinal cord in rats

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