Chimeric Self-assembling Nanofiber Containing Bone Marrow Homing Peptide’s Motif Induces Motor Neuron Recovery in Animal Model of Chronic Spinal Cord Injury; an In Vitro and In Vivo Investigation

2015 ◽  
Vol 53 (5) ◽  
pp. 3298-3308 ◽  
Author(s):  
Shima Tavakol ◽  
Reza Saber ◽  
Elham Hoveizi ◽  
Hadi Aligholi ◽  
Jafar Ai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Animal Model ◽  
Motor Neuron ◽  
Chronic Spinal Cord Injury ◽  
Self Assembling ◽  
Cord Injury

scholarly journals Adrenergic Receptors Modulate Motoneuron Excitability, Sensory Synaptic Transmission and Muscle Spasms After Chronic Spinal Cord Injury

2011 ◽  
Vol 105 (1) ◽  
pp. 410-422 ◽  
Author(s):  
M. M. Rank ◽  
K. C. Murray ◽  
M. J. Stephens ◽  
J. D'Amico ◽  
M. A. Gorassini ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Adrenergic Receptors ◽  
Receptor Activity ◽  
Chronic Spinal Cord Injury ◽  
Motoneuron Excitability ◽  
Cord Injury ◽  
Muscle Spasms

The brain stem provides most of the noradrenaline (NA) present in the spinal cord, which functions to both increase spinal motoneuron excitability and inhibit sensory afferent transmission to motoneurons (excitatory postsynaptic potentials; EPSPs). NA increases motoneuron excitability by facilitating calcium-mediated persistent inward currents (Ca PICs) that are crucial for sustained motoneuron firing. Spinal cord transection eliminates most NA and accordingly causes an immediate loss of PICs and emergence of exaggerated EPSPs. However, with time PICs recover, and thus the exaggerated EPSPs can then readily trigger these PICs, which in turn produce muscle spasms. Here we examined the contribution of adrenergic receptors to spasms in chronic spinal rats. Selective activation of the α1A adrenergic receptor with the agonists methoxamine or A61603 facilitated Ca PIC and spasm activity, recorded both in vivo and in vitro. In contrast, the α2 receptor agonists clonidine and UK14303 did not facilitate Ca PICs, but did decrease the EPSPs that trigger spasms. Moreover, in the absence of agonists, spasms recorded in vivo were inhibited by the α1 receptor antagonists WB4010, prazosin, and REC15/2739, and increased by the α2 receptor antagonist RX821001, suggesting that both adrenergic receptors were endogenously active. In contrast, spasm activity recorded in the isolated in vitro cord was inhibited only by the α1 antagonists that block constitutive receptor activity (activity in the absence of NA; inverse agonists, WB4010 and prazosin) and not by the neutral antagonist REC15/2739, which only blocks conventional NA-mediated receptor activity. RX821001 had no effect in vitro even though it is an α2 receptor inverse agonist. Our results suggest that after chronic spinal cord injury Ca PICs and spasms are facilitated, in part, by constitutive activity in α1 adrenergic receptors. Additionally, peripherally derived NA (or similar ligand) activates both α1 and α2 adrenergic receptors, controlling PICs and EPSPs, respectively.

scholarly journals A Collagen-Based Scaffold for Promoting Neural Plasticity in a Rat Model of Spinal Cord Injury

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2245
Author(s):  
Jue-Zong Yeh ◽  
Ding-Han Wang ◽  
Juin-Hong Cherng ◽  
Yi-Wen Wang ◽  
Gang-Yi Fan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Neural Plasticity ◽  
Collagen Scaffold ◽  
Glial Scar ◽  
Beneficial Effects ◽  
Cord Injury

In spinal cord injury (SCI) therapy, glial scarring formed by activated astrocytes is a primary problem that needs to be solved to enhance axonal regeneration. In this study, we developed and used a collagen scaffold for glial scar replacement to create an appropriate environment in an SCI rat model and determined whether neural plasticity can be manipulated using this approach. We used four experimental groups, as follows: SCI-collagen scaffold, SCI control, normal spinal cord-collagen scaffold, and normal control. The collagen scaffold showed excellent in vitro and in vivo biocompatibility. Immunofluorescence staining revealed increased expression of neurofilament and fibronectin and reduced expression of glial fibrillary acidic protein and anti-chondroitin sulfate in the collagen scaffold-treated SCI rats at 1 and 4 weeks post-implantation compared with that in untreated SCI control. This indicates that the collagen scaffold implantation promoted neuronal survival and axonal growth within the injured site and prevented glial scar formation by controlling astrocyte production for their normal functioning. Our study highlights the feasibility of using the collagen scaffold in SCI repair. The collagen scaffold was found to exert beneficial effects on neuronal activity and may help in manipulating synaptic plasticity, implying its great potential for clinical application in SCI.

scholarly journals Immunosuppressants Affect Human Neural Stem Cells In Vitro but Not in an In Vivo Model of Spinal Cord Injury

2013 ◽  
Vol 2 (10) ◽  
pp. 731-744 ◽  
Author(s):  
Christopher J. Sontag ◽  
Hal X. Nguyen ◽  
Noriko Kamei ◽  
Nobuko Uchida ◽  
Aileen J. Anderson ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Neural Stem Cells ◽  
In Vivo Model ◽  
Human Neural Stem Cells ◽  
Cord Injury

scholarly journals Depolarization and electrical stimulation enhance in vitro and in vivo sensory axon growth after spinal cord injury

2018 ◽  
Vol 300 ◽  
pp. 247-258 ◽  
Author(s):  
Ioana Goganau ◽  
Beatrice Sandner ◽  
Norbert Weidner ◽  
Karim Fouad ◽  
Armin Blesch
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Axon Growth ◽  
Sensory Axon ◽  
Cord Injury

scholarly journals Cytokine and Growth Factor Activation In Vivo and In Vitro after Spinal Cord Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
Elisa Garcia ◽  
Jorge Aguilar-Cevallos ◽  
Raul Silva-Garcia ◽  
Antonio Ibarra
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Critical Role ◽  
Glutamate Excitotoxicity ◽  
Signaling Proteins ◽  
Neurodegenerative Process ◽  
Cord Injury ◽  
Ion Imbalance

Spinal cord injury results in a life-disrupting series of deleterious interconnected mechanisms encompassed by the primary and secondary injury. These events are mediated by the upregulation of genes with roles in inflammation, transcription, and signaling proteins. In particular, cytokines and growth factors are signaling proteins that have important roles in the pathophysiology of SCI. The balance between the proinflammatory and anti-inflammatory effects of these molecules plays a critical role in the progression and outcome of the lesion. The excessive inflammatory Th1 and Th17 phenotypes observed after SCI tilt the scale towards a proinflammatory environment, which exacerbates the deleterious mechanisms present after the injury. These mechanisms include the disruption of the spinal cord blood barrier, edema and ion imbalance, in particular intracellular calcium and sodium concentrations, glutamate excitotoxicity, free radicals, and the inflammatory response contributing to the neurodegenerative process which is characterized by demyelination and apoptosis of neuronal tissue.

Functional Outcome of Bone Marrow Stem Cells (CD45+/CD34−) After Cell Therapy in Chronic Spinal Cord Injury in Wistar Rats

2008 ◽  
Vol 40 (3) ◽  
pp. 845-846 ◽  
Author(s):  
K.A.T. Carvalho ◽  
E.N. Vialle ◽  
G.H.G. Moreira ◽  
R.C. Cunha ◽  
R.B. Simeoni ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Cell Therapy ◽  
Functional Outcome ◽  
Wistar Rats ◽  
Bone Marrow Stem Cells ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury

scholarly journals Docosahexaenoic Acid-Loaded Polylactic Acid Core-Shell Nanofiber Membranes for Regenerative Medicine after Spinal Cord Injury: In Vitro and In Vivo Study

2020 ◽  
Vol 21 (19) ◽  
pp. 7031
Author(s):  
Zhuo-Hao Liu ◽  
Yin-Cheng Huang ◽  
Chang-Yi Kuo ◽  
Chao-Ying Kuo ◽  
Chieh-Yu Chin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Docosahexaenoic Acid ◽  
Neurite Outgrowth ◽  
Polylactic Acid ◽  
In Vivo Study ◽  
Core Shell ◽  
Cord Injury

Spinal cord injury (SCI) is associated with disability and a drastic decrease in quality of life for affected individuals. Previous studies support the idea that docosahexaenoic acid (DHA)-based pharmacological approach is a promising therapeutic strategy for the management of acute SCI. We postulated that a nanostructured material for controlled delivery of DHA at the lesion site may be well suited for this purpose. Toward this end, we prepare drug-loaded fibrous mats made of core-shell nanofibers by electrospinning, which contained a polylactic acid (PLA) shell for encapsulation of DHA within the core, for delivery of DHA in situ. In vitro study confirmed sustained DHA release from PLA/DHA core-shell nanofiber membrane (CSNM) for up to 36 days, which could significantly increase neurite outgrowth from primary cortical neurons in 3 days. This is supported by the upregulation of brain-derived neurotropic factor (BDNF) and neurotrophin-3 (NT-3) neural marker genes from qRT-PCR analysis. Most importantly, the sustained release of DHA could significantly increase the neurite outgrowth length from cortical neuron cells in 7 days when co-cultured with PLA/DHA CSNM, compared with cells cultured with 3 μM DHA. From in vivo study with a SCI model created in rats, implantation of PLA/DHA CSNM could significantly improve neurological functions revealed by behavior assessment in comparison with the control (no treatment) and the PLA CSNM groups. According to histological analysis, PLA/DHA CSNM also effectively reduced neuron loss and increased serotonergic nerve sprouting. Taken together, the PLA/DHA CSNM may provide a nanostructured drug delivery system for DHA and contribute to neuroprotection and promoting neuroplasticity change following SCI.

scholarly journals Autologous Bone Marrow-Derived Cell Therapy Combined with Physical Therapy Induces Functional Improvement in Chronic Spinal Cord Injury Patients

2014 ◽  
Vol 23 (6) ◽  
pp. 729-745 ◽  
Author(s):  
Wael Abo El-Kheir ◽  
Hala Gabr ◽  
Mohamed Reda Awad ◽  
Osama Ghannam ◽  
Yousef Barakat ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Physical Therapy ◽  
Cell Therapy ◽  
Autologous Bone Marrow ◽  
Functional Improvement ◽  
Chronic Spinal Cord Injury ◽  
Cord Injury ◽  
Autologous Bone
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