Combined effect of Cerium oxide nanoparticles loaded scaffold and photobiomodulation therapy on pain and neuronal regeneration following spinal cord injury: an experimental study.

BACKGROUND: Spinal cord injury (SCI) remained one of the challenges to treat due to its complicated mechanisms. Photobiomodulation therapy (PBMT) accelerates neuronal regeneration. Cerium oxide nanoparticles (CeONPs) also eliminate free radicals in the environment. The present study aims to introduce a combined treatment method of making PCL scaffolds as microenvironments, seeded with CeONPs and the PBMT technique for SCI treatment. METHODS: The surgical hemi-section was used to induce SCI. Immediately after the SCI induction, the scaffold (Sc) was loaded with CeONPs implanted. PBMT began 30 min after SCI induction and lasted for up to 4 weeks. Fifty-six male rats were randomly divided into seven groups. Glial fibrillary acidic protein (GFAP) (an astrocyte marker), Connexin 43 (Con43) (a member of the gap junction), and gap junctions (GJ) (a marker for the transfer of ions and small molecules) expressions were evaluated. The behavioral evaluation was performed by BBB, Acetone, Von Frey, and radiant heat tests. RESULT: The SC + Nano + PBMT group exhibited the most remarkable recovery outcomes. Thermal hyperalgesia responses were mitigated, with the combined approach displaying the most effective relief. Mechanical allodynia and cold allodynia responses were also attenuated by treatments, demonstrating potential pain management benefits. CONCLUSION: These findings highlight the potential of PBMT, combined with CeONPs-loaded scaffolds, in promoting functional motor recovery and alleviating pain-related responses following SCI. The study underscores the intricate interplay between various interventions and their cumulative effects, informing future research directions for enhancing neural repair and pain management strategies in SCI contexts.

Systemic vascular photobiomodulation accelerates the recovery of motor activity in rats following spinal cord injury.

OBJECTIVES: Spinal cord injury (SCI) causes the discontinuity of the spinal canal, leading to functional and sensorial losses in areas below the injury, which are often irreversible. Photobiomodulation (PBM) can enhance the neuromuscular repair process, especially in cases of peripheral nerve injuries. However, there is little knowledge regarding the effects of this therapeutic modality on recovery following a SCI, especially the noninvasive systemic form denominated vascular PBM (VPBM). To analyze the effects of VPBM in the immediate, acute and intermediate phases following a compression-induced SCI on morphological aspects of neuromuscular tissue repair, functional recovery and the protein expression of brain-derived neurotrophic factor (BDNF). METHODS: Wistar rats were divided into five groups: control, SCI, SCI + VPBM-Im (immediate administration of VPBM), SCI + VPBM-2h (VPBM administered 2 h after injury) and SCI + VPBM-14d (VPBM administered 14 days after injury). VPBM was administered in the region of the caudal vein/artery with low-level laser (AsGaAl, 780 nm, 80 J/cm², 40 mW for 80 s, totaling an energy of 3.2 J over a single point) for 14 consecutive days. During the analysis periods (1, 3, 7, 14, 21, 28 and 35 days after injury), functioning was evaluated using the Basso-Beattie-Bresnahan (BBB) index. At the end of each experimental period, blood samples were collected for the determination of the concentration of circulating BDNF using ELISA. Muscle tissue and nerve tissue samples were also extracted for morphological and histological analyses using H&E staining. RESULTS: SCI + VPBM-Im and SCI + VPBM-2 h led to the recovery of motor function beginning on the 7th day after injury (p < 0.05), an increase in the cross-sectional area (CSA) of the muscle fibers in the second week (p < 0.05) and an increase in muscle fiber diameter beginning on Day 14 (p < 0.05). Early irradiation had a greater effect on the reduction in the size of the cavity, with stabilization of the cavity found on Day 7 (p < 0.05). Considering the circulating BDNF levels, no changes was found during the experimental periods. CONCLUSION: The present results showed that VPBM was capable of modulating morphological and functional recovery following SCI, especially when administered early. The positive effects on functional recovery were demonstrated by the BBB index; the reestablishment of the structure of the muscle and nerve tissue was demonstrated by the preservation of CSA and diameter of muscle fiber and reduction in the area of the injury (cavity size) respectively. Thus, noninvasive VPBM may be an important component of treatment for spinal cord injuries.

Photobiomodulation and diffusing optical fiber on spinal cord's impact on nerve cells from normal spinal cord tissue in piglets.

Experts have proven that photobiological regulation therapy for spinal cord injury promotes the spinal repair following injury. The traditional irradiation therapy mode is indirect (percutaneous irradiation), which could significantly lower the effective use of light energy. In earlier studies, we developed an implantable optical fiber that one can embed above the spinal cord lamina, and the light directly is cast onto the surface of the spinal cord in a way that can dramatically improve energy use. Nonetheless, it remains to be seen whether near-infrared light diffused by embedded optical fiber can have side effects on the surrounding nerve cells. Given this, we implanted optical fiber on the lamina of a normal spinal cord to observe the structural integrity of the tissue using morphological staining; we also used immunohistochemistry to detect inflammatory factors. Considering the existing studies, we meant to determine that the light energy diffused by embedded optical fiber has no side effect on the normal tissue. The results of this study will lay a foundation for the clinical application of the treatment of spinal cord injury by near-infrared light irradiation.

The effect of low-level laser therapy on pathophysiology and locomotor recovery after traumatic spinal cord injuries: a systematic review and meta-analysis.

This study was designed to determine the effective therapeutic parameters and evaluate the regenerative potential of low-level laser therapy (LLLT) after traumatic spinal cord injuries (TSCIs) in animal studies. The EMBASE and MEDLINE databases were searched on October 5, 2019, and followed with an update on January 2, 2021. All animal studies discussing the effect of LLLT on main pathophysiological events after TSCI, including inflammation, axon growth, remyelination, glial scar formation, cavity size, and locomotor recovery, were included. For statistical analysis, we used mean difference with 95% confidence intervals for locomotor recovery. In total, 19 articles were included based on our criteria. The results showed that regardless of laser type, laser beams with a wavelength between 600 and 850 nm significantly suppress inflammation and led inflammatory cells to M2 polarization and wound healing. Also, laser therapy using these wavelengths for more than 2 weeks significantly improved axon regeneration and remyelination. Improvement of locomotor recovery was more efficient using wavelengths less than 700 nm (SMD = 1.21; 95%CI: 0.09, 2.33; p = 0.03), lasers with energy densities less than 100 J/cm2 (SMD = 1.72; 95%CI: 0.84, 2.59; p = 0.0001) and treatment duration between 1 and 2 weeks (SMD = 2.21; 95%CI: 1.24, 3.19; p < 0.00001). The LLLT showed promising potential to modulate pathophysiological events and recovery after TSCI, although there was heterogeneity in study design and reporting methods, which should be considered in future studies.

Clinical safety study of photobiomodulation in acute spinal cord injury by scattering fiber.

The study aimed to design a reliable and straightforward PBM method by implanting a medical scattering fiber above surgically exposed spinal cord in SCI patients. Moreover, the safety of this method was examined. Twelve patients with acute SCI (ASIA B) requiring posterior decompression were recruited. The medical scattering fiber was implanted above the spinal cord, and was continuously irradiated at 810 nm, 300 mW, 30 min/day, once per day for 7 days. The vital signs (temperature, blood pressure, respiratory rate, heart rate, and oxygen saturation), infection indicators (WBC, NEUT, hs-CRP, and PCT), photo-allergic reaction indicators (Eosinophil and Basophil), coagulation function indicators (PT, APTT, TT) and neurological stability indicators (ASIA sensory and motor scores) were recorded to evaluate the safety of PBM. Three months after surgery, 12 patients completed follow-up. In our study, direct PBM on SCI site did not cause clinically pathologic changes in vital signs of the patients. All patients had higher WBC, NEUT, and hs-CRP at day 3 during irradiation than those before surgery, and returned to normal at day 7. The changes in Eosinophil and Basophil that were closely associated with allergic reactions were within normal limits throughout the course of irradiation. The coagulation function (PT, APTT, and TT) of patients were also in the normal range. The ASIA sensory and motor scores of all patients had no changes throughout the irradiation process. However, in the follow-up, both ASIA sensory and motor scores of all patients had minor improvement than those in pre-irradiation, and 7 patients had adverse events, but they were not considered to be related to PBM. Our study might firstly employ direct PBM in the SCI by using scattered optical fibers. In a limited sample size, our study concluded that direct PBM at the site of SCI would not produce adverse effects within the appropriate irradiation parameters. The method is safe, feasible, and does not add additional trauma to the patient. Our preliminary study might provide a new methodology for the clinical PBM treatment of acute SCI.

Effects of photobiomodulation combined with MSCs transplantation on the repair of spinal cord injury in rat.

Stem cell transplantation has shown promising regenerative effects against neural injury, and photobiomodulation (PBM) can aid tissue recovery. This study aims to evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and laser alone or combined on spinal cord injury (SCI). The animals were divided into SCI, hUCMSCs, laser treatment (LASER) and combination treatment (hUCMSCs + LASER) groups. Cell-enriched grafts of hUCMSCs (1 × 106 cells/ml) were injected at the site of antecedent trauma in SCI model rats. A 2 cm2 damaged area was irradiated with 630 nm laser at 100 mW/cm2 power for 20 min. Locomotion was evaluated using Basso-Beattie-Bresnahan (BBB) scores, and neurofilament repair were monitored by histological staining and diffusion tensor imaging (DTI). First, after SCI, the motor function of each group was restored with different degrees, the combination treatment significantly increased the BBB scores compared to either monotherapy. In addition, Nissl bodies were more numerous, and the nerve fibers were longer and thicker in the combination treatment group. Consistent with this, the in situ expression of NF-200 and glial fibrillary acidic protein in the damaged area was the highest in the combination treatment group. Finally, DTI showed that the combination therapy optimally improved neurofilament structure and arrangement. These results may show that the combination of PBM and hUCMSCs transplantation is a feasible strategy for reducing secondary damage and promoting functional recovery following SCI.

Photobiomodulation Therapy Inhibit the Activation and Secretory of Astrocytes by Altering Macrophage Polarization.

Spinal cord injury (SCI) stimulates reactive astrogliosis and the infiltration of macrophages, which interact with each other at the injured area. We previously found Photobiomodulation (PBM) significantly decreases the number of M1 macrophages at the injured area of SCI. But the exact nature of the astrocyte response following PBM and relationship with the macrophage have not been explored in detail. In this study, a BALB/c mice model with standardized bilateral spinal cord compression and a macrophage-astrocyte co-culture model were applied to study effects of PBM on astrocytes. Results showed that PBM inhibit the expression of the astrocyte markers glial fibrillary acidic protein (GFAP) and the secretion of chondroitin sulfate proteoglycans (CSPG) in the para-epicenter area, decrease the number of M1 macrophage in vivo. The in vitro experiments indicated M1 macrophages promote the cell viability of astrocytes and the expression of CSPG. However, PBM significantly inhibited the expression of GFAP, decreased activation of astrocyte, and downregulated the expression of CSPG by regulating M1 macrophages. These results demonstrate that PBM may regulate the interaction between macrophages and astrocytes after spinal cord injury, which inhibited the formation of glial scar.

Sensory and motor responses after photobiomodulation associated with physiotherapy in patients with incomplete spinal cord injury: clinical, randomized trial.

Complete or incomplete spinal cord injury (SCI) results in permanent neurological deficits due to the interruption of nerve impulses, causing the loss of motor and sensory function, which leads to a reduction in quality of life. The focus of rehabilitation for such individuals is to improve quality of life and promote functional recovery. Photobiomodulation (PBM) has proved to be promising complementary treatment in cases of SCI. The aim of the present study was to investigate the effects of PBM combined with physiotherapy on sensory-motor responses below the level of the injury and quality of life in individuals with SCI. Thirty participants were randomized for allocation to the PBM group (active PBM + physiotherapy) or sham group (sham PBM + physiotherapy). Physiotherapy was administered three times a week. Sensitivity and motor skills were evaluated using the ASIA impairment scale. Quality of life was assessed using the WHOQOL-BREF questionnaire. The data were analyzed with the level of significance set to 5%. Improvements in sensitivity and an increase in the perception of muscle contraction were found in the active PBM group 30 days after treatment compared with the sham group. The results of the WHOQOL-BREF questionnaire revealed a significant difference in general quality of life favoring the active PBM group over the sham group after treatment. Physiotherapy combined with PBM leads to better sensory-motor recovery in patients with SCI as well as a better perception of health and quality of life. Trial registration identifier: NCT03031223.

Label-Free Spectral Imaging Unveils Biochemical Mechanisms of Low-Level Laser Therapy on Spinal Cord Injury.

BACKGROUND/AIMS: Low-level laser therapy (LLLT) leads to complex photochemical responses during the healing process of spinal cord injury (SCI). Confocal Raman Microspectral Imaging (in combination with multivariate analysis) was adopted to illustrate the underlying biochemical mechanisms of LLLT treatment on a SCI rat model. METHODS: Using transversal tissue sections, the Raman spectra can identify areas neighboring the injury site, glial scar, cavity, and unharmed white matter, as well as their correlated cellular alterations, such as demyelination and up-regulation of chondroitin sulfate proteoglycans (CSPGs). Multivariate data analysis methods are used to depict the underlying therapeutic effects by highlighting the detailed content and distribution variations of the biochemical constituents. RESULTS: It is confirmed that photon-tissue interactions might lead to a decay of the inhibitory response to remyelination by suppressing CSPG expression, as also morphologically demonstrated by reduced glial scar and cavity areas. An inter-group comparison semi-quantitatively confirms changes in lipids, phosphatidic acid, CSPGs, and cholesterol during SCI and its LLLT treatment, paving the way for in vitro and in vivo understanding of the biochemical changes accompanying pathobiological SCI events. CONCLUSION: The achieved results in this work not only have once again proved the well-known cellular mechanisms of SCI, but further illustrate the underlying biochemical variability during LLLT treatment, which provide a sound basis for developing real-time Raman methodologies to monitor the efficacy of the SCI LLLT treatment.

Photobiomodulation improves motor response in patients with spinal cord injury submitted to electromyographic evaluation: randomized clinical trial.

Photobiomodulation is a treatment that has been widely used in neurotrauma and neurodegenerative diseases. In the present study, low-level laser therapy was administered to patients with spinal cord injury. Twenty-five individuals were divided into two groups: placebo photobiomodulation plus physiotherapy and active photobiomodulation plus physiotherapy. Electromyographic evaluations were performed before and after 12 sessions of phototherapy as well as 30 days after the end of treatment. In the active phototherapy group, median frequency values of the brachial biceps and femoral quadriceps muscles were higher at rest and during isotonic contraction 30 days after photobiomodulation (p = 0.0258). No significant results were found regarding the rest and isotonic conditions in the pre-photobiomodulation period (p = 0.950) or immediately following photobiomodulation (p = 0.262). The data provide evidence that phototherapy improves motor responses in individuals with spinal cord injury, as demonstrated by differences in the EMG signal before and after treatment. TRIAL REGISTRATION: NCT 03031223.

Low-dose fractionated irradiation promotes axonal regeneration beyond reactive gliosis and facilitates locomotor function recovery after spinal cord injury in beagle dogs.

Injury to the adult central nervous system (CNS) results in the formation of glial scar tissues. Glial scar-induced failure of regenerative axon pathfinding may limit axon regrowth beyond the lesion site and cause incorrect reinnervation and dystrophic appearance of stalled growth after CNS trauma. Glial scars also upregulate chondroitin sulphate proteoglycans (CSPGs) and expression of proinflammatory factor(s) that form a barrier to axonal regeneration. Therefore, interventions for glial scarring are an attractive strategy for augmenting axonal sprouting and regeneration and overcoming the physical and molecular barriers impeding functional repair. The glial reaction occurs shortly after spinal cord injury (SCI) and can persist for days or weeks with upregulation of cell cycle proteins. In this study, we utilised Beagle dogs to establish a preclinical SCI model and examine the efficacy of low-dose fractionated irradiation (LDI) treatment, which was performed once a day for 14 days (2 Gy per dose, 28 Gy in total). Low-dose fractionated irradiation is a stable method for suppressing cell activation and proliferation through interference in the cell cycle. Our results demonstrated that LDI could reduce astrocyte and microglia activation/proliferation and attenuate CSPGs and IL-1ß expression. Low-dose fractionated irradiation also promoted and provided a pathway for long-distance axon regeneration beyond the lesion site, induced reinnervation of axonal targets and restored locomotor function after SCI in Beagle dogs. Taken together, our findings suggest that LDI would be a promising therapeutic strategy for targeting glial scarring, promoting axon regeneration and facilitating reconstruction of functional circuits after SCI.

Modeling in vivo relative biological effectiveness in particle therapy for clinically relevant endpoints.

BACKGROUND: The relative biological effectiveness (RBE) of particle therapy compared to photon radiotherapy is known to be variable but the exact dependencies are still subject to debate. In vitro data suggested that RBE is to a large extend independent of ion type if parametrized by the beam quality Q. This study analyzed the RBE dependence of pre-clinical data on late toxicity with an emphasis on the beam quality. MATERIAL AND METHODS: Published pre-clinical RBE dose-response data of the spinal cord following one and two fractions of photon and carbon ion irradiation were compiled. The beam quality for each treatment condition was obtained from Monte Carlo simulations. The αp and ßp parameters of the linear-quadratic (LQ) model for particle irradiation were determined from the pre-clinical data and was provided as a function of Q. An introduced model proposed αp to increase linearly with Q and ßp to remain constant. RBE values predicted by the model were compared to the published data. RESULTS: The αp parameter was highly correlated with Q (R2 = 0.96) with a linear slope of 0.019 Gy-1. No significant variation of ßp with Q was found. RBE and Q were also highly correlated (R2 = 0.98) for one and two fractions. The (extrapolated) RBE at Q = 0 (theoretical photon limit) for one and two fractions was 1.22 and significantly larger than 1 (p = .004). The model reproduced the dependence of RBE on fractionation well. CONCLUSIONS: Fraction dose and beam quality Q were sufficient to describe the RBE variability for a late toxicity model within a carbon ion treatment field. Assuming the independence of the identified RBE parameters on the ion type might suggest the translation of variable (pre-) clinical RBE data from carbon ion to proton therapy.

Effects of different fluences of low-level laser therapy in an experimental model of spinal cord injury in rats.

The aim of this study was to evaluate the in vivo response of different fluences of low-level laser therapy (LLLT) on the area of the injury, inflammatory markers, and functional recovery using an experimental model of traumatic spinal cord injury (SCI). Thirty two rats were randomly divided into four experimental groups: control group (CG), laser-treated group 500 J/cm2 (L-500), laser-treated group 750 J/cm2 (L-750), and laser-treated group 1000 J/cm2 (L-1000). SCI was performed by an impactor equipment (between the ninth and tenth thoracic vertebrae), with a pressure of 150 kdyn. Afterwards, the injured region was irradiated daily for seven consecutive sessions, using an 808-nm laser, at the respective fluence of each experimental groups. Motor function and tactile sensitivity were performed on days 1 and 7 post-surgery. Animals were euthanized on the eighth day after injury, and the samples were retrieved for histological and immunohistochemistry analyses. Functional evaluation and tactile sensitivity were improved after LLLT, at the higher fluence. Additionally, LLLT, at 750 and 1000 J/cm2, reduces the lesion volume and modulates the inflammatory process with decrease of CD-68 protein expression. These results suggest that LLLT at higher doses was effective in promoting functional recovery and modulating inflammatory process in the spinal cord of rats after SCI.

Heterotopic ossification of the shoulder joint following spinal cord injury: an analysis of 21 cases after single-dose radiation therapy.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: Heterotopic ossification (HO) affecting the hips is a common complaint of patients suffering traumatic spinal cord injury. However, the incidence of HO of the shoulder is considerably rare. In this context, we report on our results of 13 patients with a total of 21 cases of shoulder HO and single-dose radiation therapy. SETTING: Department of Spinal Cord Injury and Department of General and Trauma Surgery, BG-University Hospital Bergmannsheil Bochum, Ruhr-University Bochum, Germany. METHODS: The study group consists of 12 male and 1 female patient with a mean age of 55.5 years (range from 24 to 81 years; s.d.=14.5). Primary outcome measures were defined as the number of HO relapses and the number of side or adverse effects in relation to the radiation therapy. RESULTS: At the time of latest follow-up during hospitalization, the mean shoulder flexion was 92.1° while mean abduction was 94.5°. The average external rotation was 26.4°. No HO recurrence occurred and none of the patients suffered any adverse effects related to radiation therapy. CONCLUSIONS: In conclusion, single-dose radiation therapy in the treatment of shoulder HO due to spinal cord injury is an effective and reliable method, although the risk of secondary side effects related to the radiation therapy remain unknown.

Development of heterotopic ossifications, blood markers and outcome after radiation therapy in spinal cord injured patients.

STUDY DESIGN: Retrospective study. OBJECTIVES: This study was implemented to detect risk factors for the developing of heterotopic ossifications (HOs) in spinal cord injury (SCI) patients. SETTING: This study was conducted in Murnau, Germany. METHODS: All patients from 2008-2012 with acute SCI were routinely examined by ultrasound of the hips every 2 weeks. The sub group of SCI patients suffering of HO of the hips were extracted and the incidence of developing an HO was calculated. Parameters like age, level of injury, ASIA Impairment Scale (AIS), duration time of accident until diagnosis of HO, Brooker stage, localization of HO (magnetic resonance imaging (MRI)) and symptoms like thrombosis, emboli, decrease of range of motion (ROM), dermal symptoms, swelling, increase in D-Dimere level, were evaluated. Also accompanying injuries of the brain, lung and extremities were recorded. RESULTS: From January 2008 until January 2012, 575 patients with an acute and traumatic SCI were treated in our Department. During this period 32 HOs were detected in the muscles surrounding the hip. In 10 cases a single side and in 22 cases both sides were affected. A total of 26 patients were detected showing up a Brooker 0, two patients Brooker 1, and five patients a Brooker stage >2. The adductor muscles showed an edema in 19 cases and the quadriceps muscles were affected in 15 cases. 26% of all SCI patients showed AIS A status, but in patients who developed HO, 64% have had an AIS A status. 19% of patients with a HO were AIS B and 9.5% showed an AIS C and D. Regarding the level of injury the distribution of patients suffering of HO was comparable to the distribution of SCI patients without HO. In mean HO were detected 9 weeks after SCI and no new HO were found after the 22nd (n=1) week of injury. Clinical symptoms such as swelling, pain, redness or decrease in ROM or increase in D-Dimere levels were seen in 24 cases. Accompanying injuries like brain injury and lung contusions were found in 83% of patients developing HO. The incidence of thrombosis was comparable to SCI patients without HO. One patient with no accompanying injuries or clinical symptoms was detected by routinely performed ultrasound. CONCLUSIONS: The risk of developing HO in patients with traumatic SCI is 5.5% but increases when accompanying injuries of the brain and lung occur. Patients with a neurological status of AIS A must also be quoted as risk patients. When considering the described risk factors and clinical symptoms, 96% of all HO can be detected.

"Low-intensity laser therapy effect on the recovery of traumatic spinal cord injury".

Scientific advances have been made to optimize the healing process in spinal cord injury. Studies have been developed to obtain effective treatments in controlling the secondary injury that occurs after spinal cord injury, which substantially changes the prognosis. Low-intensity laser therapy (LILT) has been applied in neuroscience due to its anti-inflammatory effects on biological tissue in the repairing process. Few studies have been made associating LILT to the spinal cord injury. The objective of this study was to investigate the effect of the LILT (GaAlAs laser-780 nm) on the locomotor functional recovery, histomorphometric, and histopathological changes of the spinal cord after moderate traumatic injury in rats (spinal cord injury at T9 and T10). Thirty-one adult Wistar rats were used, which were divided into seven groups: control without surgery (n = 3), control surgery (n = 3), laser 6 h after surgery (n = 5), laser 48 h after surgery (n = 5), medullar lesion (n = 5) without phototherapy, medullar lesion + laser 6 h after surgery (n = 5), and medullar lesion + laser 48 h after surgery (n = 5). The assessment of the motor function was performed using Basso, Beattie, and Bresnahan (BBB) scale and adapted Sciatic Functional Index (aSFI). The assessment of urinary dysfunction was clinically performed. After 21 days postoperative, the animals were euthanized for histological and histomorphometric analysis of the spinal cord. The results showed faster motor evolution in rats with spinal contusion treated with LILT, maintenance of the effectiveness of the urinary system, and preservation of nerve tissue in the lesion area, with a notorious inflammation control and increased number of nerve cells and connections. In conclusion, positive effects on spinal cord recovery after moderate traumatic spinal cord injury were shown after LILT.

Photobiomodulation Increases M2-Type Polarization of Macrophages by Inhibiting Versican Production After Spinal Cord Injury.

Spinal cord injury (SCI) is a catastrophic accidence with little effective treatment, and inflammation played an important role in that. Previous studies showed photobiomodulation (PBM) could effectively downregulate the process of inflammation with modification of macrophage polarization after SCI; however, the potential mechanism behind that is still unclear. In the presented study, we aimed to investigate the effect of PBM on the expression level of versican, a matrix molecular believed to be associated with inflammation, and tried to find the mechanism on how that could regulate the inflammation process. Using immunofluorescence technique and western blot, we found the expression level of versican is increased after injury and markedly downregulated by irradiation treatment. Using virus intrathecal injection, we found the knock-down of versican could produce the effect similar to that of PBM and might have an effect on inflammation and macrophage polarization after SCI. To further verify the deduction, we peptide the supernatant of astrocytes to induce M0, M1, and M2 macrophages. We found that the versican produced by astrocytes might have a role on the promotion of M2 macrophages to inflammatory polarization. Finally, we investigated the potential pathway in the regulation of M2 polarization with the induction of versican. This study tried to give an interpretation on the mechanism of inflammation inhibition for PBM in the perspective of matrix regulation. Our results might provide light on the inflammation regulation after SCI.

Effect and mechanism of terahertz irradiation in repairing spinal cord injury in mice.

SIGNIFICANCE: Spinal cord injury (SCI) represents a serious trauma to the central nervous system. Terahertz (THz) irradiation is an emerging technique, it has potential application prospects in the treatment of central nervous system diseases. AIM: We report on the investigation of the effect and mechanism of THz irradiation in repairing SCI in mice. APPROACH: The effect of THz in SCI was evaluated by the expression of inflammatory factors, the mouse behavioral scale (BMS), and immunofluorescence staining. After RNA sequencing (RNA-seq), we determined the differentially expressed genes (DEGs) and performed GO and KEGG analysis. RESULTS: After THz irradiation, the inflammatory response, the behavioral function, and the severity of SCI recovered well, indicating that THz irradiation can effectively promote the repair of SCI. GO and KEGG results show that genes related to inflammation, immune regulation, and IL-17 signaling pathway may play an important role in this process. CONCLUSIONS: THz irradiation can effectively promote the repair of SCI. Genes related to inflammation, immune regulation, and IL-17 signaling pathway may play an important role in this process.

X-ray Irradiation Improves Neurological Function Recovery of Injured Spinal Cord by Inhibiting Inflammation and Glial Scar Formation.

Spinal cord injury (SCI) is a common clinical disease that can cause permanent disruption of nerve function. Inflammation and glial scar formation influence the recovery of injured spinal cord. X-ray irradiation can reduce inflammation, inhibit cell proliferation and increase cell apoptosis. However, the regulatory effects of X-ray irradiation on inflammation and glial scars and the underlying molecular mechanisms are still unclear. This study was aimed to investigate the therapeutic effect and molecular mechanism of X-ray irradiation on spinal cord injury. Behavioural experiments showed that X-ray irradiation can promote the recovery of nerve function after SCI. X-ray irradiation inhibited the inflammatory response by reducing the expression of inflammatory factors (TNF-α and IL-1ß) at the lesion site, thereby reducing neuronal apoptosis. X-ray irradiation inhibited the formation of the glial scar (GFAP and vimentin) in the lesion. P38MAPK and Akt signalling pathways were involved in these processes. Furthermore, the 10 Gy dose had the most significant effects among the 2 Gy, 10 Gy and 20 Gy doses. In summary, X-ray irradiation may exert an active therapeutic effect on SCI by inhibiting inflammation and glial scar formation, which may be related to the inhibition of p38MAPK and Akt signalling pathways.

Effects of photobiomodulation in experimental spinal cord injury models: A systematic review.

This systematic review investigated the repercussions of photobiomodulation using low-level laser therapy (LLLT) for the treatment of spinal cord injury (SCI) in experimental models. Studies were identified from relevant databases published between January 2009 and December 2021. Nineteen original articles were selected and 68.4% used light at an infrared wavelength. There was a considerable variation of the power used (from 25 to 200 mW), total application time (8-3000 s) and total energy (0.3-450 J). In 79% of the studies, irradiation was initiated immediately after or within 2 h of the SCI, and treatment time ranged continuously from 5 to 21 days. In conclusion, LLLT can be an auxiliary therapy in the treatment of SCI, playing a neuroprotective role, enabling functional recovery, increasing the concentration of nerve connections around the injury site and reducing pro-inflammatory cytokines. However, there is a need for standardization in the dosimetric parameters.