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 Sustained delivery of neurotrophic factors to treat spinal cord injury

2021 ◽  
Vol 12 (1) ◽  
pp. 494-511
Author(s):  
Aikeremujiang Muheremu ◽  
Li Shu ◽  
Jing Liang ◽  
Abudunaibi Aili ◽  
Kan Jiang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Neurotrophic Factors ◽  
Neurotrophic Factor ◽  
Neural Regeneration ◽  
Sustained Delivery ◽  
Neural Repair ◽  
Cord Injury ◽  
Psychological Harm

Abstract Acute spinal cord injury (SCI) is a devastating condition that results in tremendous physical and psychological harm and a series of socioeconomic problems. Although neurons in the spinal cord need neurotrophic factors for their survival and development to reestablish their connections with their original targets, endogenous neurotrophic factors are scarce and the sustainable delivery of exogeneous neurotrophic factors is challenging. The widely studied neurotrophic factors such as brain-derived neurotrophic factor, neurotrophin-3, nerve growth factor, ciliary neurotrophic factor, basic fibroblast growth factor, and glial cell-derived neurotrophic factor have a relatively short cycle that is not sufficient enough for functionally significant neural regeneration after SCI. In the past decades, scholars have tried a variety of cellular and viral vehicles as well as tissue engineering scaffolds to safely and sustainably deliver those necessary neurotrophic factors to the injury site, and achieved satisfactory neural repair and functional recovery on many occasions. Here, we review the neurotrophic factors that have been used in trials to treat SCI, and vehicles that were commonly used for their sustained delivery.

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.

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 Photobiomodulation Promotes Repair Following Spinal Cord Injury by Regulating the Transformation of A1/A2 Reactive Astrocytes

2021 ◽  
Vol 15 ◽  
Author(s):  
Xuankang Wang ◽  
Zhihao Zhang ◽  
Zhijie Zhu ◽  
Zhuowen Liang ◽  
Xiaoshuang Zuo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Motor Function ◽  
Function Analysis ◽  
Reactive Astrocytes ◽  
Male Rats ◽  
Dependent Manner ◽  
Astrocyte Activation ◽  
Cord Injury

After spinal cord injury (SCI), reactive astrocytes can be classified into two distinctive phenotypes according to their different functions: neurotoxic (A1) astrocytes and neuroprotective (A2) astrocytes. Our previous studies proved that photobiomodulation (PBM) can promote motor function recovery and improve tissue repair after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM contributes to repair after SCI by regulating the activation of astrocytes. Male rats subjected to clip-compression SCI were treated with PBM for two consecutive weeks, and the results showed that recovery of motor function was improved, the lesion cavity size was reduced, and the number of neurons retained was increased. We determined the time course of A1/A2 astrocyte activation after SCI by RNA sequencing (RNA-Seq) and verified that PBM inhibited A1 astrocyte activation and promoted A2 astrocyte activation at 7 days postinjury (dpi) and 14 dpi. Subsequently, potential signaling pathways related to A1/A2 astrocyte activation were identified by GO function analysis and KEGG pathway analysis and then studied in animal experiments and preliminarily analyzed in cultured astrocytes. Next, we observed that the expression of basic fibroblast growth factor (bFGF) and transforming growth factor-β (TGF-β) was upregulated by PBM and that both factors contributed to the transformation of A1/A2 astrocytes in a dose-dependent manner. Finally, we found that PBM reduced the neurotoxicity of A1 astrocytes to dorsal root ganglion (DRG) neurons. In conclusion, PBM can promote better recovery after SCI, which may be related to the transformation of A1/A2 reactive astrocytes.

scholarly journals Systemic Administration of Fibroblast Growth Factor 21 Improves the Recovery of Spinal Cord Injury (SCI) in Rats and Attenuates SCI-Induced Autophagy

2021 ◽  
Vol 11 ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Lin Ye ◽  
Weiyang Ying ◽  
Jiahui Ye ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Functional Recovery ◽  
Nerve Cells ◽  
Systemic Administration ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Cord Injury

Protecting the death of nerve cells is an essential tactic for spinal cord injury (SCI) repair. Recent studies show that nerve growth factors can reduce the death of nerve cells and promote the healing of nerve injury. To investigate the conducive effect of fibroblast growth factor 21 (FGF21) on SCI repair. FGF21 proteins were systemically delivered into rat model of SCI via tail vein injection. We found that administration of FGF21 significantly promoted the functional recovery of SCI as assessed by BBB scale and inclined plane test, and attenuated cell death in the injured area by histopathological examination with Nissl staining. This was accompanied with increased expression of NeuN, GAP43 and NF200, and deceased expression of GFAP. Interestingly, FGF21 was found to attenuate the elevated expression level of the autophagy marker LC3-II (microtubules associated protein 1 light chain 3-II) induced by SCI in a dose-dependent manner. These data show that FGF21 promotes the functional recovery of SCI via restraining injury-induced cell autophagy, suggesting that systemic administration of FGF21 could have a therapeutic potential for SCI repair.

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