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 DEPENDENCE OF THE RESTORATIVE EFFECT OF MACROPOROUS POLY(N-[2-HYDROXYPROPYL]-METHACRYLAMIDE HYDROGEL ON THE SEVERITY OF EXPERIMENTAL LACERATIVE SPINAL CORD INJURY

2021 ◽  
Vol 127 (4) ◽  
pp. 8-21
Author(s):  
Ibrahim Abdallah ◽  
Volodymyr Мedvediev ◽  
Nataliya Draguntsova ◽  
Nana Voitenko ◽  
Vitaliy Tsymbaliuk
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Severe Trauma ◽  
Individual Characteristics ◽  
Male Rats ◽  
Study Results ◽  
Cord Injury ◽  
Hydroxypropyl Methacrylamide ◽  
Immediate Implantation

restoration of the spinal cord function presents a most severe biomedical issue nowadays. The aim of the study was to detect the macroporous poly(N-[2-hydroxypropyl]-methacrylamide hydrogel (PHPMA-hydrogel, HG) restorative effect dependence on the severity of the laceration spinal cord injury in young organisms. The male rats sample (~1-month-old, ~50 g, inbred Wistar line) was represented with 4 experimental groups: 1) spinal cord lateral hemisection at the level of ~Т12–Т13 segments (Sect; n=11); 2) spinal cord lateral hemiexcision ~1 mm long at the similar level (Exc; n=8); 3) spinal cord lateral hemisection at the similar level with immediate implantation of the hydrogel fragment into the trauma region (HGsect; n=11); 4) spinal cord lateral hemiexcision at the similar level with immediate implantation of the hydrogel fragment into the affected region (HGexс; n=6). The motor function and spasticity of the paretic hindlimb was estimated respectively by the technically modified Basso–Beattie–Bresnahan (ВВВ) and Ashworth, conditionally blinded to individual characteristics of all operated animals and previous study results. The observation lasted for ~5 months. The criteria of non-inclusion were as follows: the ipsilateral hindlimb function level in a week after the injury >9 points ВВВ, and the contralateral hindlimb function level during prolonged period ≤14 points ВВВ. The results were interpreted and presented according to the standardized time scale with interpolatory representation of the motor function and spasticity individual level in certain cases. Asymptotic stage differences between the studied groups and subgroups were stated during the first three weeks as well as in 8 weeks and 3 months after the injury. We found out that in a week after injury the motor function level in group Exc made up 0.9±0.5 points ВВВ, in group HGexc — 3.6±1.2 points, in group Sect — 5.9±1.1 points, in group HGsect — 6.0±1.0 points. In 5 months the motor function level in group Sect made up 9.5±1.0 points ВВВ, in group HGsect — 9.5±1.1 points, in group Exc — 0.8±0.3 points, in group HGexc — 4.5±1.8 points. At the same study stage the spasticity level in groups Sect and HGsect was, respectively, 0.8±0.2 and 0.8±0.3 points Ashworth, in group HGexc — 1.8±0.7 points, in group Exc — 3.6±0.3 points. Throughout the study no significant differences in groups Sect and HGsect have been detected, and in groups Exc і HGexc such differences were detected only in 5 weeks after the injury. The considerable difference of spasticity in groups Sect and HGsect was noted in 1 week after the injury, in groups HGexc and Exc — during first 2 months of the experiment. In groups Sect and Exc reliable difference of both motor function and spasticity level was found at all study stages. In groups HGsect and HGexc considerable difference of the motor function level was characteristic at all stages, except for the end of the 1st and 7th weeks, whereas spasticity level differences throughout the study remained insignificant. So, the tested hydrogel in young organisms shows positive effect only with severe trauma stages accompanied with extensive spinal cord defect.

scholarly journals Evaluation of PTEN Inhibitor Following Spinal Cord Injury on Recovery of Voiding Efficiency and Motor Function Observed by Regeneration in Spinal Cord

2020 ◽  
Vol 24 (Suppl 2) ◽  
pp. 104-110
Author(s):  
Young Sam Cho ◽  
Su Jin Kim ◽  
Khae Hawn Kim
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Growth Factors ◽  
Growth Factor ◽  
Motor Function ◽  
Walking Ability ◽  
Voiding Function ◽  
Walking Test ◽  
Cord Injury ◽  
Scale Test

Purpose: Neurogenic bladder (NB) associated with spinal cord injury (SCI) is a serious health problem. However, no effective treatment has been developed for SCI patients with NB. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibitors have been proposed as a promising option for inducing neural regeneration. Therefore, we investigated the effects of a tissue gene nerve (TGN), PTEN inhibitor, on voiding function, motor function, and the expression of growth factors after SCI.Methods: In this experiment, female rats were randomly divided into 3 groups (n=10 in each group): the sham-operation group, the SCI-induced group, and the SCI-induced and TGN-treated group. Cystometry; the Basso, Beattie, and Bresnahan (BBB) scale test; the ladder walking test; hematoxylin and eosin staining; and Western blotting for brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) were performed to evaluate functional and molecular changes.Results: After SCI, the rats exhibited decreased walking ability according to the BBB scale test and impaired coordinative function according to the ladder walking test. The PTEN inhibitor promoted enhanced walking ability and coordinative function. Cystometry showed voiding impairment after SCI and improved voiding function was observed after PTEN treatment. Overexpression of VEGF, BDNF, and NGF were observed after SCI. Administration of PTEN inhibitors significantly attenuated the overexpression of growth factors due to SCI.Conclusion: PTEN inhibitor treatment diminished the overexpression of growth factors and promoted the repair of damaged tissue. PTEN inhibitor-treated rats also showed improved motor function and improved voiding function. Therefore, we suggest TGN as a new therapeutic agent that can be applied after SCI.

scholarly journals Upregulation of Vascular Endothelial Growth Factor Receptors Flt-1 and Flk-1 Following Acute Spinal Cord Contusion in Rats

2007 ◽  
Vol 55 (8) ◽  
pp. 821-830 ◽  
Author(s):  
Jeong-Sun Choi ◽  
Ha-Young Kim ◽  
Jung-Ho Cha ◽  
Jae-Youn Choi ◽  
Sang In Park ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Reactive Astrocytes ◽  
Pcr Analysis ◽  
Vascular Endothelial ◽  
Cord Injury ◽  
Contusion Injury ◽  
Endothelial Growth Factor

To investigate the possible role of vascular endothelial growth factor (VEGF) in the injured spinal cord, we analyzed the distribution and time course of the two tyrosine kinase receptors for VEGF, Flt-1 and Flk-1, in the rat spinal cord following contusion injury using a weight-drop impactor. The semi-quantitative RT-PCR analysis of Flt-1 and Flk-1 in the spinal cord showed slight upregulation of these receptors following spinal cord injury. Although mRNAs for Flt-1 and Flk-1 were constitutively expressed in neurons, vascular endothelial cells, and some astrocytes in laminectomy control rats, their upregulation was induced in association with microglia/macrophages and reactive astrocytes in the vicinity of the lesion within 1 day in rats with a contusion injury and persisted for at least 14 days. The spatiotemporal expression of Flt-1 in the contused spinal cord mirrored that of Flk-1 expression. In the early phase of spinal cord injury, upregulation of Flt-1 and Flk-1 mRNA occurred in microglia/macrophages that infiltrated the lesion. In addition, the expression of both receptors increased progressively in reactive astrocytes within the vicinity of the lesion, predominately in the white matter, and almost all reactive astrocytes coexpressed Flt-1 or Flk-1 and nestin. These results suggest that VEGF may be involved in the inflammatory response and the astroglial reaction to contusion injuries of the spinal cord via specific VEGF receptors. (J Histochem Cytochem 55: 821–830, 2007)

scholarly journals Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xuankang Wang ◽  
Xin Li ◽  
Xiaoshuang Zuo ◽  
Zhuowen Liang ◽  
Tan Ding ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Male Rats ◽  
In Vitro Experiments ◽  
Post Injury ◽  
Stat3 Pathway ◽  
Cord Injury ◽  
Recovery Of Motor Function

Abstract Background Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. Methods Male Sprague–Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. Results PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. Conclusion Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway

2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Inflammatory Factors ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Apoptosis And Inflammation

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.

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