scholarly journals Heparin-Binding Growth-Associated Molecule (Pleiotrophin) Affects Sensory Signaling and Selected Motor Functions in Mouse Model of Anatomically Incomplete Cervical Spinal Cord Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Natalia Kulesskaya ◽  
Dmitry Molotkov ◽  
Sonny Sliepen ◽  
Ekaterina Mugantseva ◽  
Arturo Garcia Horsman ◽  
...  

Heparin-binding growth-associated molecule (pleiotrophin) is a neurite outgrowth-promoting secretory protein that lines developing fiber tracts in juvenile CNS (central nervous system). Previously, we have shown that heparin-binding growth-associated molecule (HB-GAM) reverses the CSPG (chondroitin sulfate proteoglycan) inhibition on neurite outgrowth in the culture medium of primary CNS neurons and enhances axon growth through the injured spinal cord in mice demonstrated by two-photon imaging. In this study, we have started studies on the possible role of HB-GAM in enhancing functional recovery after incomplete spinal cord injury (SCI) using cervical lateral hemisection and hemicontusion mouse models. In vivo imaging of blood-oxygen-level-dependent (BOLD) signals associated with functional activity in the somatosensory cortex was used to assess the sensory functions during vibrotactile hind paw stimulation. The signal displays an exaggerated response in animals with lateral hemisection that recovers to the level seen in the sham-operated mice by injection of HB-GAM to the trauma site. The effect of HB-GAM treatment on sensory-motor functions was assessed by performance in demanding behavioral tests requiring integration of afferent and efferent signaling with central coordination. Administration of HB-GAM either by direct injection into the trauma site or by intrathecal injection improves the climbing abilities in animals with cervical hemisection and in addition enhances the grip strength in animals with lateral hemicontusion without affecting the spontaneous locomotor activity. Recovery of sensory signaling in the sensorimotor cortex by HB-GAM to the level of sham-operated mice may contribute to the improvement of skilled locomotion requiring integration of spatiotemporal signals in the somatosensory cortex.

2018 ◽  
Vol 300 ◽  
pp. 247-258 ◽  
Author(s):  
Ioana Goganau ◽  
Beatrice Sandner ◽  
Norbert Weidner ◽  
Karim Fouad ◽  
Armin Blesch

2015 ◽  
Vol 21 (2) ◽  
pp. 55-61 ◽  
Author(s):  
Hasan Çelik ◽  
Senem Mutevelizade ◽  
Ferhat Harman ◽  
Gökhan Yılmaz ◽  
Mehmet Zafer Berkman

2020 ◽  
Vol 21 (19) ◽  
pp. 7031
Author(s):  
Zhuo-Hao Liu ◽  
Yin-Cheng Huang ◽  
Chang-Yi Kuo ◽  
Chao-Ying Kuo ◽  
Chieh-Yu Chin ◽  
...  

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.


2007 ◽  
Vol 6 (2) ◽  
pp. 133-140 ◽  
Author(s):  
Eric M. Horn ◽  
Michael Beaumont ◽  
Xiao Zheng Shu ◽  
Adrian Harvey ◽  
Glenn D. Prestwich ◽  
...  

Object Therapies that use bioactive materials as replacement extracellular matrices may hold the potential to mitigate the inhibition of regeneration observed after central nervous system trauma. Hyaluronic acid (HA), a nonsulfated glycosaminoglycan ubiquitous in all tissues, was investigated as a potential neural tissue engineering matrix. Methods Chick dorsal root ganglia were cultured in 3D hydrogel matrices composed of cross-linked thiol-modified HA or fibrin. Samples were cultured and images were acquired at 48-, 60-, and 192-hour time points. Images of all samples were analyzed at 48 hours of incubation to quantify the extent of neurite growth. Cultures in cross-linked thiolated HA exhibited more than a 50% increase in neurite length compared with fibrin samples. Furthermore, cross-linked thiolated HA supported neurites for the entire duration of the culture period, whereas fibrin cultures exhibited collapsed and degenerating extensions beyond 60 hours. Two concentrations of the thiolated HA (0.5 and 1%) were then placed at the site of a complete thoracic spinal cord transection in rats. The ability of the polymer to promote regeneration was tested using motor evoked potentials, retrograde axonal labeling, and behavioral assessments. There were no differences in any of the parameters between rats treated with the polymer and controls. Conclusions The use of a cross-linked HA scaffold promoted robust neurite outgrowth. Although there was no benefit from the polymer in a rodent spinal cord injury model, the findings in this study represent an early step in the development of semisynthetic extracellular matrice scaffolds for the treatment of neuronal injury.


1985 ◽  
Vol 63 (1) ◽  
pp. 125-127 ◽  
Author(s):  
Brett A. Scott ◽  
Zelig Weinstein ◽  
Robert Chiteman ◽  
Morris W. Pulliam

✓ Intractable lower extremity spasms after spinal cord injury is a significant source of morbidity. A case of refractory spasticity in paraplegia was successfully converted to flaccid paraplegia by intrathecal injection of phenol and glycerin in metrizamide. This chemical rhizolysis is simple and effective, and the presence of metrizamide allows both fluoroscopic guidance for accurate intrathecal phenol placement and good miscibility with cerebrospinal fluid. A brief comparative review of alternative therapeutic modalities is presented.


2020 ◽  
pp. 107385842096627 ◽  
Author(s):  
Petr Krupa ◽  
Ahad M. Siddiqui ◽  
Peter J. Grahn ◽  
Riazul Islam ◽  
Bingkun K. Chen ◽  
...  

Evidence from preclinical and clinical research suggest that neuromodulation technologies can facilitate the sublesional spinal networks, isolated from supraspinal commands after spinal cord injury (SCI), by reestablishing the levels of excitability and enabling descending motor signals via residual connections. Herein, we evaluate available evidence that sublesional and supralesional spinal circuits could form a translesional spinal network after SCI. We further discuss evidence of translesional network reorganization after SCI in the presence of sensory inputs during motor training. In this review, we evaluate potential mechanisms that underlie translesional circuitry reorganization during neuromodulation and rehabilitation in order to enable motor functions after SCI. We discuss the potential of neuromodulation technologies to engage various components that comprise the translesional network, their functional recovery after SCI, and the implications of the concept of translesional network in development of future neuromodulation, rehabilitation, and neuroprosthetics technologies.


2009 ◽  
Vol 26 (7) ◽  
pp. 955-964 ◽  
Author(s):  
Tomohiro Miyashita ◽  
Masao Koda ◽  
Keiko Kitajo ◽  
Masashi Yamazaki ◽  
Kazuhisa Takahashi ◽  
...  

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