A combinatorial approach to modulate microenvironment toward regeneration and repair after spinal cord injury in rats

Bhattacharyya, Supti; Dinda, Amit Kumar; Vishnubhatla, Sreenivas; Anwar, Mohammad Faiyaz; Jain, Suman

doi:10.1016/j.neulet.2020.135500

Cited by 17 publications

(15 citation statements)

References 31 publications

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“…We have analysed data using peak to peak analysis feature of LabChart software. [10] We have found precise MEP and SSEP responses with minimum stimuli at AP-2.5 mm, ML-1.5 mm and AP-2.5 mm and ML-2.8 mm, respectively.…”

Section: Resultsmentioning

confidence: 49%

“…We have observed a complete abolition of the motor as well as SSEP 5 weeks after severe contusion injury to the thoracic spinal cord. [10] We propose that this technique could be a reliable measure to assess the function of the sensory and motor system. Any intervention to improve motor or sensory function can also be assessed based on analysis of evoked potentials.…”

Section: Discussionmentioning

confidence: 99%

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Recording of motor and somatosensory evoked potential in an anaesthetised Wistar rat using digital polyrite system

Bhattacharyya

Kochhar

Jain

2022

IJPP

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Objectives: The aim of this article is to explain the detailed methodology to record Motor evoked potential (MEP) and somatosensory evoked potential (SSEP) in adult albino Wistar rat, male (200–250 g) which has not been defined previously. Materials and Methods: We have standardised recording of both MEP and SSEP in these rats under anaesthesia on ADI digital polyrite system. Results: Evoked potentials have been widely studied in spinal cord injured patients to estimate the degree of injury and to establish a predictive measure of functional recovery. MEPs and SSEPs, arising from the motor cortex or peripheral nerve and generated either by direct electrical stimulation or by transcranial magnetic stimulation, have been advocated as a reliable indicator of descending and ascending pathway integrity. In the rat brain, there is a physical overlap between the motor and somatosensory cortex. Hence, our objective was to identify the exact area for stimulation in the cortex where we could record maximum response with the application of minimum electrical stimulation. Conclusion: The recording of MEP and SSEP together provides a powerful neurological technique to monitor the tracts of the spinal cord.

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Section: Resultsmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Recording of motor and somatosensory evoked potential in an anaesthetised Wistar rat using digital polyrite system

Bhattacharyya

Kochhar

Jain

2022

IJPP

Self Cite

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“…Among them, neurons are vital for reconstruction of the neural network and proper function. It has been reported that the majority of the endogenous or exogenous NSPCs in the injury site tend to differentiate into glial cells rather than neurons, resulting in limited success in functional recovery. , To solve this issue, various attempts have been made to alleviate the inhibitory microenvironment for improving neuronal differentiation in vivo . , In our previous studies, epidermal growth factor receptor (EGFR) neutralizing antibody was used for Col scaffold functionalization to block EGFR-related signaling triggered by myelin-associated proteins. , The functionalized Col scaffolds improved neuronal differentiation of exogenous NSPCs embedded in the scaffolds and promoted functional recovery of SCI rats. In a follow-up study, we demonstrated that EGFR neutralizing antibody functionalized Col scaffolds induced neurogenesis of endogenous NSPCs, leading to locomotion recovery .…”

Section: Resultsmentioning

confidence: 99%

Adhesive, Stretchable, and Spatiotemporal Delivery Fibrous Hydrogels Harness Endogenous Neural Stem/Progenitor Cells for Spinal Cord Injury Repair

et al. 2021

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Aligned fibrous hydrogels capable of recruiting endogenous neural stem/progenitor cells (NSPCs) show great promise in spinal cord injury (SCI) repair. However, the hydrogels suffer from severe issues in close contact with the transected nerve stumps and harnessing the NSPC fate in the lesion microenvironment. Herein, we report aligned collagen-fibrin (Col-FB) fibrous hydrogels with stretchable property, adhesive behavior, and stromal cell-derived factor-1α (SDF1α)/paclitaxel (PTX) spatiotemporal delivery capability. The resultant Col-FB fibrous hydrogels exhibited 1.98 times longer elongation at break (230%), 2.55 times lower Young's modulus (17.93 ± 1.16 KPa), and 2.21 times greater adhesive strength (3.45 ± 0.48 KPa) than collagen (Col) fibrous hydrogels. The soft aligned fibrous hydrogels simulate the oriented microstructure and soft tissue feature of a natural spinal cord and provide elasticity and adhesivity to ensure a persistent close contact with host stumps. The repair of complete transection SCI in rats demonstrates that "middle-tobilateral" SDF1α gradient release induced endogenous NSPC migration to the lesion site in 10 days, and SDF1α/PTX sequential release promoted neuronal differentiation of the recruited NSPCs over 8 weeks, leading to hind limb locomotion recovery. The presented strategy was proved to be efficient for harnessing endogenous NSPCs, which facilitate SCI repair significantly.

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“…However, SCI rats with BMSCs exosomes injection could partly increase the number of Nissl bodies, while BMSCs exosomes did not work in the Shh-knockdown SCI rats while the BBB score changed in rats post-SCI thus corroborating the role of these exosomes in augmenting neural regeneration with a critical role of Shh in SCI. GAP-43, a neuronal phosphoprotein, plays an essential role in nerve growth [ 29 ]. In the current study, we identified up-regulation of GAP-43 after SCI as a response by spinal cord tissue for neuro-protection.…”

Section: Discussionmentioning

confidence: 99%

Repair of spinal cord injury in rats via exosomes from bone mesenchymal stem cells requires sonic hedgehog

Jia

Yang

et al. 2021

Regenerative Therapy

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Objective The loss of neural ability leading to subsequent diminishing of motor function and the impairment below the location of the injury is a result of the SCI (Spinal Cord Injury). Among the many therapeutic agents for SCI, the exosomes considered as extracellular vesicles seem to be the most promising. Sonic Hedgehog (Shh) is an exosome-carrying protein. This Study's purpose was to identify whether Shh is required for exosomes from BMSCs (mesenchymal stem cells of the bone) and plays a protective effect on SCI. Methods Spinal cord injection with shRNA Shh-adeno associated virus (sh-Shh-AAV) were used to silence Shh. Exosomes were extracted from BMSCs. Rats that had suffered SCI were given intravenous injections of exosomes through the veins of the tail. Immunohistochemistry was used to identify the expression of Shh glycoprotein molecule as well as the expression of Gli-1 (glioma-associated oncogene homolog 1) in the rat spinal cord tissues. Western blot was performed to measure the levels of growth associated protein-43 (GAP-43). The BBB (Basso Beattie Bresnahan) score was used to assess the motor functions of the hind legs. In the same manner, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling or TUNEL and Nissl Staining was deployed to assess the level of regeneration of neurons and assess the level of histopathological damage in the tissues of the Spinal Cord. Results In the case of the rats with SCI, the levels of display of Gli-1 and Shh showed dramatic improvement after the BMSCs exosome injections. In comparison to rats with SCI, the subjects of BMSCs exosomes group showed an improvement in their SCI, including a higher BBB score and Nissl body count, increasing GAP-43 expression, along with a much-decreased number of cells that suffered apoptosis. While the exosome effect on Spinal Cord Injury was completely ineffective in rats that had Shh silencing. Conclusions Exosomes secreted from BMSCs showed great effectiveness in the SCI healing with a vital involvement of Shh in this repair.

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A combinatorial approach to modulate microenvironment toward regeneration and repair after spinal cord injury in rats

Cited by 17 publications

References 31 publications

Recording of motor and somatosensory evoked potential in an anaesthetised Wistar rat using digital polyrite system

Recording of motor and somatosensory evoked potential in an anaesthetised Wistar rat using digital polyrite system

Adhesive, Stretchable, and Spatiotemporal Delivery Fibrous Hydrogels Harness Endogenous Neural Stem/Progenitor Cells for Spinal Cord Injury Repair

Repair of spinal cord injury in rats via exosomes from bone mesenchymal stem cells requires sonic hedgehog

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