Sustained delivery of bioactive neurotrophin-3 to the injured spinal cord

2015 ◽  
Vol 3 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Irja Elliott Donaghue ◽  
Charles H. Tator ◽  
Molly S. Shoichet
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Sustained Release ◽  
Sustained Delivery ◽  
Injured Spinal Cord ◽  
Hydrogel Composite ◽  
Neurotrophin 3 ◽  
Cord Injury

The sustained release of neurotrophin-3 from a nanoparticle/hydrogel composite resulted in functional and tissue benefit after compressive spinal cord injury.

Sustained release of neurotrophin-3 via calcium phosphate-coated sutures promotes axonal regeneration after spinal cord injury

2016 ◽  
Vol 94 (7) ◽  
pp. 645-652 ◽  
Author(s):  
Amgad Hanna ◽  
Daniel L. Thompson ◽  
Daniel J. Hellenbrand ◽  
Jae-Sung Lee ◽  
Casey J. Madura ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Calcium Phosphate ◽  
Sustained Release ◽  
Axonal Regeneration ◽  
Neurotrophin 3 ◽  
Cord Injury

Localized and sustained release of brain-derived neurotrophic factor from injectable hydrogel/microparticle composites fosters spinal learning after spinal cord injury

2016 ◽  
Vol 4 (47) ◽  
pp. 7560-7571 ◽  
Author(s):  
Zin Z. Khaing ◽  
Nikunj K. Agrawal ◽  
James H. Park ◽  
Shangjing Xin ◽  
Glendon C. Plumton ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Sustained Release ◽  
Sustained Delivery ◽  
Mediated Learning ◽  
Injectable Hydrogel ◽  
Cord Injury ◽  
Spinal Learning ◽  
Hydrogel Microparticle

Injectable hydrogel allows for sustained delivery of growth factor resulting in spinal mediated learning after injury.

scholarly journals Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

2020 ◽  
Vol 9 (4) ◽  
pp. 1221 ◽  
Author(s):  
Jacek M. Kwiecien ◽  
Liqiang Zhang ◽  
Jordan R. Yaron ◽  
Lauren N. Schutz ◽  
Christian J. Kwiecien-Delaney ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Low Dose ◽  
Dorsal Column ◽  
Neurological Deficits ◽  
Sustained Delivery ◽  
Post Surgery ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI.

scholarly journals Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Qi Han ◽  
Josue D. Ordaz ◽  
Nai-Kui Liu ◽  
Zoe Richardson ◽  
Wei Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Neurons ◽  
Enhanced Recovery ◽  
Neural Pathways ◽  
Locomotor Recovery ◽  
Neurotrophin 3 ◽  
Cord Injury ◽  
Dendritic Atrophy ◽  
Descending Projections

AbstractLocomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.

scholarly journals Overexpression of Rictor in the injured spinal cord promotes functional recovery in a rat model of spinal cord injury

2020 ◽  
Vol 34 (5) ◽  
pp. 6984-6998
Author(s):  
Ningning Chen ◽  
Pengxiang Zhou ◽  
Xizhe Liu ◽  
Jiachun Li ◽  
Yong Wan ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Rat Model ◽  
Injured Spinal Cord ◽  
Cord Injury

scholarly journals B-RAFV600E Inhibitor Dabrafenib Attenuates RIPK3-Mediated Necroptosis and Promotes Functional Recovery after Spinal Cord Injury

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1582 ◽  
Author(s):  
Takehiro Sugaya ◽  
Haruo Kanno ◽  
Michiharu Matsuda ◽  
Kyoichi Handa ◽  
Satoshi Tateda ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Tissue Damage ◽  
Neuroprotective Effect ◽  
Neural Tissue ◽  
Injured Spinal Cord ◽  
Thoracic Spinal Cord ◽  
Thoracic Spinal ◽  
Cord Injury

The receptor-interacting protein kinase 3 (RIPK3) is a key regulator of necroptosis and is involved in various pathologies of human diseases. We previously reported that RIPK3 expression is upregulated in various neural cells at the lesions and necroptosis contributed to secondary neural tissue damage after spinal cord injury (SCI). Interestingly, recent studies have shown that the B-RAFV600E inhibitor dabrafenib has a function to selectively inhibit RIPK3 and prevents necroptosis in various disease models. In the present study, using a mouse model of thoracic spinal cord contusion injury, we demonstrate that dabrafenib administration in the acute phase significantly inhibites RIPK3-mediated necroptosis in the injured spinal cord. The administration of dabrafenib attenuated secondary neural tissue damage, such as demyelination, neuronal loss, and axonal damage, following SCI. Importantly, the neuroprotective effect of dabrafenib dramatically improved the recovery of locomotor and sensory functions after SCI. Furthermore, the electrophysiological assessment of the injured spinal cord objectively confirmed that the functional recovery was enhanced by dabrafenib. These findings suggest that the B-RAFV600E inhibitor dabrafenib attenuates RIPK3-mediated necroptosis to provide a neuroprotective effect and promotes functional recovery after SCI. The administration of dabrafenib may be a novel therapeutic strategy for treating patients with SCI in the future.

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