scholarly journals Intravital Assessment of Cells Responses to Conducting Polymer-Coated Carbon Microfibres for Bridging Spinal Cord Injury

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 73
Author(s):  
Bilal El Waly ◽  
Vincent Escarrat ◽  
Jimena Perez-Sanchez ◽  
Jaspreet Kaur ◽  
Florence Pelletier ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Immune Cell ◽  
Two Photon ◽  
Sensory Axons ◽  
Promising Therapeutic Approach ◽  
Cord Injury ◽  
Biochemical Signals ◽  
Coated Carbon ◽  
Striking Effect

The extension of the lesion following spinal cord injury (SCI) poses a major challenge for regenerating axons, which must grow across several centimetres of damaged tissue in the absence of ordered guidance cues. Biofunctionalized electroconducting microfibres (MFs) that provide biochemical signals, as well as electrical and mechanical cues, offer a promising therapeutic approach to help axons overcome this blind journey. We used poly(3,4-ethylenedioxythiophene)-coated carbon MFs functionalized with cell adhesion molecules and growth factors to bridge the spinal cord after a partial unilateral dorsal quadrant lesion (PUDQL) in mice and followed cellular responses by intravital two-photon (2P) imaging through a spinal glass window. Thy1-CFP//LysM-EGFP//CD11c-EYFP triple transgenic reporter animals allowed real time simultaneous monitoring of axons, myeloid cells and microglial cells in the vicinity of the implanted MFs. MF biocompatibility was confirmed by the absence of inflammatory storm after implantation. We found that the sprouting of sensory axons was significantly accelerated by the implantation of functionalized MFs after PUDQL. Their implantation produced better axon alignment compared to random and misrouted axon regeneration that occurred in the absence of MF, with a most striking effect occurring two months after injury. Importantly, we observed differences in the intensity and composition of the innate immune response in comparison to PUDQL-only animals. A significant decrease of immune cell density was found in MF-implanted mice one month after lesion along with a higher ratio of monocyte-derived dendritic cells whose differentiation was accelerated. Therefore, functionalized carbon MFs promote the beneficial immune responses required for neural tissue repair, providing an encouraging strategy for SCI management.

Epidural electrical stimulation to facilitate locomotor recovery after spinal cord injury

2021 ◽  
Author(s):  
Johannie Audet ◽  
Charly G. Lecomte
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Electrical Stimulation ◽  
Clinical Implementation ◽  
Preclinical Models ◽  
Lumbosacral Region ◽  
Locomotor Recovery ◽  
Promising Therapeutic Approach ◽  
Cord Injury ◽  
Stimulation Of

Tonic or phasic electrical epidural stimulation of the lumbosacral region of the spinal cord facilitates locomotion and standing in a variety of preclinical models with severe spinal cord injury. However, the mechanisms of epidural electrical stimulation that facilitate sensorimotor functions remain largely unknown. This review aims to address how epidural electrical stimulation interacts with spinal sensorimotor circuits and discusses the limitations that currently restrict the clinical implementation of this promising therapeutic approach.

scholarly journals Intercostal, ilioinguinal, and iliohypogastric nerve transfers for lower limb reinnervation after spinal cord injury: an anatomical feasibility and experimental study

2019 ◽  
Vol 30 (2) ◽  
pp. 268-278 ◽  
Author(s):  
Ahmed A. Toreih ◽  
Asser A. Sallam ◽  
Cherif M. Ibrahim ◽  
Ahmed I. Maaty ◽  
Mohsen M. Hassan
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Animal Studies ◽  
Femoral Nerve ◽  
Lower Limbs ◽  
Nerve Transfers ◽  
Promising Therapeutic Approach ◽  
Cord Injury ◽  
Significant Motor

OBJECTIVESpinal cord injury (SCI) has been investigated in various animal studies. One promising therapeutic approach involves the transfer of peripheral nerves originating above the level of injury into those originating below the level of injury. The purpose of the present study was to evaluate the feasibility of nerve transfers for reinnervation of lower limbs in patients suffering SCI to restore some hip and knee functions, enabling them to independently stand or even step forward with assistive devices and thus improve their quality of life.METHODSThe feasibility of transferring intercostal to gluteal nerves and the ilioinguinal and iliohypogastric nerves to femoral nerves was assessed in 5 cadavers. Then, lumbar cord hemitransection was performed below L1 in 20 dogs, followed by transfer of the 10th, 11th, and 12th intercostal and subcostal nerves to gluteal nerves and the ilioinguinal and iliohypogastric nerves to the femoral nerve in only 10 dogs (NT group). At 6 months, clinical and electrophysiological evaluations of the recipient nerves and their motor targets were performed.RESULTSThe donor nerves had sufficient length to reach the recipient nerves in a tension-free manner. At 6 months postoperatively, the mean conduction velocity of gluteal and femoral nerves, respectively, increased to 96.1% and 92.8% of the velocity in controls, and there was significant motor recovery of the quadriceps femoris and glutei.CONCLUSIONSIntercostal, ilioinguinal, and iliohypogastric nerves are suitable donors to transfer to the gluteal and femoral nerves after SCI to restore some hip and knee motor functions.

In vivo two-photon imaging reveals a role of progesterone in reducing axonal dieback after spinal cord injury in mice

2017 ◽  
Vol 116 ◽  
pp. 30-37 ◽  
Author(s):  
Zhijie Yang ◽  
Wenguang Xie ◽  
Furong Ju ◽  
Akbar khan ◽  
Shengxiang Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Two Photon ◽  
Cord Injury ◽  
Photon Imaging ◽  
Two Photon Imaging

scholarly journals MULTIMODAL NONLINEAR OPTICAL IMAGING OF CELL–MATRIX INTERACTION DURING SPINAL CORD INJURY EX VIVO

2011 ◽  
Vol 23 (03) ◽  
pp. 223-230 ◽  
Author(s):  
Yi-Cheng Huang ◽  
Te-Hsuen Chen ◽  
Wen-Chun Kuo ◽  
Sung-Hao Hsu ◽  
Yi-You Huang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Ex Vivo ◽  
Second Harmonic ◽  
Two Photon ◽  
Matrix Interaction ◽  
Cell Matrix ◽  
Photon Excitation ◽  
Cord Injury ◽  
Near Future

Neurons within spinal cord injury (SCI) are prevented from regeneration because of scar formation. Chondroitinase ABC (ChABC) was reported to promote functional recovery after spinal cord injury. However, the mechanism and the role of ChABC in the recovery are not clear. In this research, we used second harmonic generation (SHG) and two-photon excitation fluorescence (2PEF) images as probes to observe cell–matrix interaction on fibrosis after SCI followed by ChABC treatment. According to our experimental results, the enzyme ChABC could decrease cystic formation dramatically and consequently allow the spinal cord to regenerate. Using immunohistological analysis, we found that treatment with ChABC at the lesion area resulted in fewer chondroitin sulfate proteoglycans (CSPGs) remaining, longer axonal re-growth, and more new developmental neurons. Furthermore, ChABC 1 U/ml was more effective than 5 U/ml treatment. Using the noninvasive technology, SHG and 2PEF images, we could observe cell–matrix interaction clearly, not only in fixed samples but also in unfixed ex vivo samples. This technology presents a potential for clinical use in the near future.

scholarly journals Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel J. Hellenbrand ◽  
Charles M. Quinn ◽  
Zachariah J. Piper ◽  
Carolyn N. Morehouse ◽  
Jordyn A. Fixel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Immune Cell ◽  
Sensory Function ◽  
Glutamate Excitotoxicity ◽  
Secondary Injury ◽  
Extensive Literature ◽  
Secondary Damage ◽  
Cord Injury

AbstractTraumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.

scholarly journals Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Chao Wang ◽  
Lu Zhang ◽  
Jean De La Croix Ndong ◽  
Aubryanna Hettinghouse ◽  
Guodong Sun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Western Blotting ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Neurological Recovery ◽  
Post Injury ◽  
Nissl Staining ◽  
Promising Therapeutic Approach ◽  
Cord Injury

Abstract Purpose Spinal cord injury (SCI) often results in significant and catastrophic dysfunction and disability and imposes a huge economic burden on society. This study aimed to determine whether progranulin (PGRN) plays a role in the progressive damage following SCI and evaluate the potential for development of a PGRN derivative as a new therapeutic target in SCI. Methods PGRN-deficient (Gr−/−) and wild-type (WT) littermate mice were subjected to SCI using a weight-drop technique. Local PGRN expression following injury was evaluated by Western blotting and immunofluorescence. Basso Mouse Scale (BMS), inclined grid walking test, and inclined plane test were conducted at indicated time points to assess neurological recovery. Inflammation and apoptosis were examined by histology (Hematoxylin and Eosin (H&E) staining and Nissl staining, TUNEL assays, and immunofluorescence), Western blotting (from whole tissue protein for iNOS/p-p65/Bax/Bcl-2), and ex vivo ELISA (for TNFα/IL-1β/IL-6/IL-10). To identify the prophylactic and therapeutic potential of targeting PGRN, a PGRN derived small protein, Atsttrin, was conjugated to PLGA-PEG-PLGA thermosensitive hydrogel and injected into intrathecal space prior to SCI. BMS was recorded for neurological recovery and Western blotting was applied to detect the inflammatory and apoptotic proteins. Results After SCI, PGRN was highly expressed in activated macrophage/microglia and peaked at day 7 post-injury. Grn−/− mice showed a delayed neurological recovery after SCI at day 21, 28, 35, and 42 post-injury relative to WT controls. Histology, TUNEL assay, immunofluorescence, Western blotting, and ELISA all indicated that Grn−/− mice manifested uncontrolled and expanded inflammation and apoptosis. Administration of control-released Atsttrin could improve the neurological recovery and the pro-inflammatory/pro-apoptotic effect of PGRN deficiency. Conclusion PGRN deficiency exacerbates SCI by promoting neuroinflammation and cellular apoptosis, which can be alleviated by Atsttrin. Collectively, our data provide novel evidence of using PGRN derivatives as a promising therapeutic approach to improve the functional recovery for patients with spinal cord injury.

scholarly journals Gut dysbiosis impairs recovery after spinal cord injury

2016 ◽  
Vol 213 (12) ◽  
pp. 2603-2620 ◽  
Author(s):  
Kristina A. Kigerl ◽  
Jodie C.E. Hall ◽  
Lingling Wang ◽  
Xiaokui Mo ◽  
Zhongtang Yu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Gut Microbiota ◽  
Oral Delivery ◽  
Cell Activation ◽  
Immune Cell ◽  
Neurological Function ◽  
Lymphoid Tissues ◽  
Gut Dysbiosis ◽  
Cord Injury

The trillions of microbes that exist in the gastrointestinal tract have emerged as pivotal regulators of mammalian development and physiology. Disruption of this gut microbiome, a process known as dysbiosis, causes or exacerbates various diseases, but whether gut dysbiosis affects recovery of neurological function or lesion pathology after traumatic spinal cord injury (SCI) is unknown. Data in this study show that SCI increases intestinal permeability and bacterial translocation from the gut. These changes are associated with immune cell activation in gut-associated lymphoid tissues (GALTs) and significant changes in the composition of both major and minor gut bacterial taxa. Postinjury changes in gut microbiota persist for at least one month and predict the magnitude of locomotor impairment. Experimental induction of gut dysbiosis in naive mice before SCI (e.g., via oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment and spinal cord pathology after SCI. Conversely, feeding SCI mice commercial probiotics (VSL#3) enriched with lactic acid–producing bacteria triggers a protective immune response in GALTs and confers neuroprotection with improved locomotor recovery. Our data reveal a previously unknown role for the gut microbiota in influencing recovery of neurological function and neuropathology after SCI.

scholarly journals 3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Junhao Deng ◽  
Miao Li ◽  
Fanqi Meng ◽  
Zhongyang Liu ◽  
Song Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Human Placenta ◽  
Trophic Factors ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Two Photon ◽  
Cord Injury

AbstractMesenchymal stem cell (MSC) is an absorbing candidate for cell therapy in treating spinal cord injury (SCI) due to its great potential for multiple cell differentiation, mighty paracrine secretion as well as vigorous immunomodulatory effect, of which are beneficial to the improvement of functional recovery post SCI. However, the therapeutic effects of MSC on SCI have been limited because of the gradual loss of MSC stemness in the process of expanding culture. Therefore, in this study, we aimed to maintain those beneficial properties of MSC via three-dimensional spheroid cell culture and then compared them with conventionally-cultured MSCs in the treatment of SCI both in vitro and in vivo with the aid of two-photon microscope. We found that 3D human placenta-derived MSCs (3D-HPMSCs) demonstrated a significant increase in secretion of anti-inflammatory factors and trophic factors like VEGF, PDGF, FGF via QPCR and Bio-Plex assays, and showed great potentials on angiogenesis and neurite morphogenesis when co-cultured with HUVECs or DRGs in vitro. After transplantation into the injured spinal cord, 3D-HPMSCs managed to survive for the entire experiment and retained their advantageous properties in secretion, and exhibited remarkable effects on neuroprotection by minimizing the lesion cavity, inhibiting the inflammation and astrogliosis, and promoting angiogenesis. Further investigation of axonal dieback via two-photon microscope indicated that 3D-HPMSCs could effectively alleviate axonal dieback post injury. Further, mice only treated with 3D-HPMSCs obtained substantial improvement of functional recovery on electrophysiology, BMS score, and Catwalk analysis. RNA sequencing suggested that the 3D-HPMSCs structure organization-related gene was significantly changed, which was likely to potentiate the angiogenesis and inflammation regulation after SCI. These results suggest that 3D-HPMSCs may hold great potential for the treatment of SCI.

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