Response In Spinal Cord Injury Research Articles

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning.

JOURNAL/nrgr/04.03/01300535-202412000-00028/figure1/v/2024-04-08T165401Z/r/image-tiff Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022).

Sport Medicine Principles Augment Healing Response in Spinal Cord Injury in a Rat Model Treated with a Curcumin-Loaded Nanocomposite Hydrogel

In this research, the potential healing function of regular exercise on spinal cord injury healing response was investigated in a rat model. The animals were treated with curcumin-loaded chitosan nanoparticles dispersed in a calcium alginate hydrogel containing endometrial stem cells. Study showed the animals that received both regular exercise and hydrogel showed significantly better histopathological signs and functional recovery than the other groups. Histopathological studies showed that edema, vacuolation, and fibrosis were significantly lower in this group. Gene expression studies showed that the hybrid treatment upregulated the expression levels of VEGF, b-FGF, and TGF-β genes.

The NF-κB Pathway: a Focus on Inflammatory Responses in Spinal Cord Injury.

Spinal cord injury (SCI) is a type of central nervous system trauma that can lead to severe nerve injury. Inflammatory reaction after injury is an important pathological process leading to secondary injury. Long-term stimulation of inflammation can further deteriorate the microenvironment of the injured site, leading to the deterioration of neural function. Understanding the signaling pathways that regulate responses after SCI, especially inflammatory responses, is critical for the development of new therapeutic targets and approaches. Nuclear transfer factor-κB (NF-κB) has long been recognized as a key factor in regulating inflammatory responses. The NF-κB pathway is closely related to the pathological process of SCI. Inhibition of this pathway can improve the inflammatory microenvironment and promote the recovery of neural function after SCI. Therefore, the NF-κB pathway may be a potential therapeutic target for SCI. This article reviews the mechanism of inflammatory response after SCI and the characteristics of NF-κB pathway, emphasizing the effect of inhibiting NF-κB on the inflammatory response of SCI to provide a theoretical basis for the biological treatment of SCI.

Research Progress of MicroRNAs in Spinal Cord Injury

Spinal cord injury is a serious and devastating condition. Recently, research into microRNAs (miRNAs) has become increasingly exhaustive and it has been determined that they are closely related to the pathophysiological processes of spinal cord injury. They participate in the regulation of the inflammatory response of spinal cord injury, the death of neuronal cells, and the repair of neural functions, which are related to the recovery of spinal cord injury. This review focuses on the relationship between miRNA and spinal cord injury, lists miRNA-324-5p, miRNA-221 and miRNA-124, which are helpful for the repair of spinal cord injury, and finally summarizes the current research progress of miRNA-based therapies, so as to provide a foundational reference for clinical and scientific researchers.

Schwann cell-derived exosomes containing MFG-E8 modify macrophage/microglial polarization for attenuating inflammation via the SOCS3/STAT3 pathway after spinal cord injury

Macrophage/microglia polarization acts as an important part in regulating inflammatory responses in spinal cord injury (SCI). However, the regulation of inflammation of Schwann cell-derived exosomes (SCDEs) for SCI repair is still unclear. Therefore, we intend to find out the effect of SCDEs on regulating the inflammation related to macrophage polarization during the recovery of SCI. Firstly, the thesis demonstrated that SCDEs could attenuate the LPS- inflammation in BMDMs by suppressing M1 polarization and stimulating M2 polarization. Similarly, SCDEs improved functional recovery of female Wistar rats of the SCI contusion model according to BBB (Basso, Beattie, and Bresnahan) score, electrophysiological assay, and the gait analysis system of CatWalk XT. Moreover, MFG-E8 was verified as the main component of SCDEs to improve the inflammatory response by proteomic sequencing and lentiviral transfection. Improvement of the inflammatory microenvironment also inhibited neuronal apoptosis. The knockout of MFG-E8 in SCs can reverse the anti-inflammatory effects of SCDEs treatment. The SOCS3/STAT3 signaling pathway was identified to participate in upregulating M2 polarization induced by MFG-E8. In conclusion, our findings will enrich the mechanism of SCDEs in repairing SCI and provide potential applications and new insights for the clinical translation of SCDEs treatment for SCI.

Alendronate Enhances Functional Recovery after Spinal Cord Injury.

Spinal cord injury is a destructive disease characterized by motor/sensory dysfunction and severe inflammation. Alendronate is an anti-inflammatory molecule and may therefore be of benefit in the treatment of the inflammation associated with spinal cord injury. This study aimed to evaluate whether alendronate attenuates motor/sensory dysfunction and the inflammatory response in a thoracic spinal cord clip injury model. Alendronate was intraperitoneally administered at 1 mg/kg/day or 5 mg/kg/day from day (D) 0 to 28 post-injury (PI). The histopathological evaluation showed an alleviation of the inflammatory response, including the infiltration of inflammatory cells, and a decrease in gliosis. Alendronate also led to reductions in the levels of inflammation-related molecules, including mitogen-activated protein kinase, p53, pro-inflammatory cytokines, and pro-inflammatory mediators. Neuro-behavioral assessments, including the Basso, Beattie, and Bresnahan scale for locomotor function, the von Frey filament test, the hot plate test, and the cold stimulation test for sensory function, and the horizontal ladder test for sensorimotor function improved significantly in the alendronate-treated group at D28PI. Taken together, these results suggest that alendronate treatment can inhibit the inflammatory response in spinal cord injury thus improving functional responses.

Knockdown of long non-coding RNA NEAT1 relieves the inflammatory response of spinal cord injury through targeting miR-211-5p/MAPK1 axis

ABSTRACT Spinal cord injury (SCI) is a refractory disease often accompanied by inflammation. Long non-coding RNA NEAT1 (lncRNA NEAT1) was reported to be involved in the expression of the inflammasomes, while the regulatory effect of NEAT1 on SCI was poorly investigated. Herein, we carried out further studies on the pathogenesis of SCI. PC-12 cells were incubated with lipopolysaccharide (LPS) to induce inflammation. Western blotting assay was used to measure the protein expression levels. RNA expression levels were analyzed using RT-qPCR. Cell counting kit 8 and flow cytometry assays were used to separately determine the cell viability and apoptosis rate. The targeted relationships were verified by luciferase reporter and RNA pull-down assays. It was found that LPS induced inflammation in the PC-12 cells, leading to significantly higher cell apoptosis rate and lower viability, and the expression level of NEAT1 was elevated by LPS. However, knockdown of NEAT1 partially reversed the effects of LPS. Subsequently, the potential interaction between NEAT1 and miR-211-5p was validated and miR-211-5p inhibitor was further confirmed to antagonize the effects of NEAT knockdown. The downstream target gene of miR-211-5p was predicted and verified to be MAPK1. In addition, overexpression of MAPK1 was proved to antagonize the effects of NEAT1 knockdown. Taken together, the knockdown of NEAT1 remarkably alleviated the inflammation of SCI via miR-211-5p/MAPK1 axis.

Perforin affects regeneration in a mouse spinal cord injury model

Purpose of study: To study the role of the immune response in spinal cord injury, we previously investigated the effects of genetic deletion of functional T- and B-lymphocytes in recombination activating gene 2 (Rag2)-deficient mice. To dissect out another defined and more restricted component of the immune system, we now analyzed mice deficient in perforin, an enzyme with proteolytic activity expressed mainly by natural killer and cytotoxic lymphocytes. Materials and methods Locomotor outcomes in perforin-deficient (Pfp-/-) mice and wild-type littermate controls were measured after severe compression injury of the lower thoracic spinal cord up to six weeks after injury. Results According to both the Basso mouse scale score and single frame motion analysis, motor recovery of Pfp-/- mice was similar to wild-type controls. Interestingly, immunohistochemical analysis of cell types at six weeks after injury showed enhanced cholinergic reinnervation of spinal motor neurons caudal to the lesion site and neurofilament-positive structures at the injury site in Pfp-/- mice, whereas numbers of microglia/macrophages and astrocytes were decreased compared with controls. Conclusions We conclude that, although, loss of perforin does not change the locomotor outcome after injury, it beneficially affects diverse cellular features, such as number of axons, cholinergic synapses, astrocytes and microglia/macrophages at or caudal to the lesion site. Perforin’s ability to contribute to Rag2’s influence on locomotion was observed in mice doubly deficient in perforin and Rag2 which recovered better than Rag2-/- or Pfp-/- mice, suggesting that natural killer cells can cooperate with T- and B-cells in spinal cord injury.

Effect of VX‑765 on the transcriptome profile of mice spinal cords with acute injury

Previous studies have shown that caspase-1 plays an important role in the acute inflammatory response of spinal cord injury (SCI). VX-765, a novel and irreversible caspase-1 inhibitor, has been reported to effectively intervene in inflammation. However, the effect of VX-765 on genome-wide transcription in acutely injured spinal cords remains unknown. Therefore, in the present study, RNA-sequencing (RNA-Seq) was used to analyze the effect of VX-765 on the local expression of gene transcription 8 h following injury. The differentially expressed genes (DEGs) underwent enrichment analysis of functions and pathways by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, respectively. Parallel analysis of western blot confirmed that VX-765 can effectively inhibit the expression and activation of caspase-1. RNA-Seq showed that VX-765 treatment resulted in 1,137 upregulated and 1,762 downregulated DEGs. These downregulated DEGs and their associated signaling pathways, such as focal adhesion, cytokine-cytokine receptor interaction, leukocyte transendothelial migration, extracellular matrix-receptor interaction, phosphatidylinositol 3-kinase-protein kinase B, Rap1 and hypoxia inducible factor-1 signaling pathway, are mainly associated with inflammatory response, local hypoxia, macrophage differentiation, adhesion migration and apoptosis of local cells. This suggests that the application of VX-765 in the acute phase can improve the local microenvironment of SCI by inhibiting caspase-1. However, whether VX-765 can be used as a therapeutic drug for SCI requires further exploration. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA548970).

Let-7 participates in the regulation of inflammatory response in spinal cord injury through PI3K/Akt signaling pathway.

To study the potential mechanism of let-7 in participating in the regulation of inflammatory response in spinal cord injury (SCI). A total of 40 male Sprague-Dawley rats were randomly divided into four groups: group A (Sham, n=10), group B (SCI+NC, n=10), group C (SCI+antagomir, n=10), and group D (SCI+mimics, n=10). The SCI model was established via operation in all groups. After successful modeling, let-7-antagomir negative control (80 mg/kg) was intraperitoneally injected in SCI+NC group at 5 d, an equal amount of let-7-antagomir was intraperitoneally injected in SCI+antagomir group at 5 d, and an equal amount of let-7-mimics was intraperitoneally injected in SCI+mimics group at 5 d. The inflammatory cells in experimental groups and control group were observed via hematoxylin-eosin (HE) staining. At the same time, the expression of let-7 in the four groups was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), the expressions of phosphatidylinositol 3-hydroxy kinase (PI3K) and protein kinase B (Akt) in all groups were detected via Western blotting, and the inflammatory index levels in each group were detected via enzyme-linked immunosorbent assay (ELISA). In Sham group, it was observed via HE staining that there were only a few bleeding or inflammatory cells. In SCI+NC group, bleeding and inflammatory cells basically tended to be stable. There were a large number of inflammatory cells in SCI+mimics group, while there were some inflammatory cells in SCI+antagomir group, but showing a decreasing trend compared with SCI+NC group. It was found in the RT-PCR detection of let-7 expression level in all groups that the expression of let-7 significantly declined in SCI+antangomir group compared with that in Sham group and SCI+NC group, and there were significant differences (p<0.01). The expression of let-7 was significantly increased in SCI+mimics group compared with that in Sham group and SCI+NC group, and there were significant differences (p<0.01). The results of Western blotting revealed that the PI3K and Akt protein expressions were significantly decreased in SCI+mimics group compared with those in SCI+antagomir group, SCI+NC group, and Sham group (p<0.05). The ELISA results showed that the levels of inflammatory factors in SCI+mimics group, SCI+antagomir group, and SCI+NC group were significantly higher than those in Sham group. In SCI+mimics group, the levels of inflammatory factors were abnormally high and reached extremely significant levels (p<0.05), indicating that let-7 promotes the inflammatory response after SCI. Let-7 participates in the regulation of inflammatory response in SCI through the PI3K/Akt signaling pathway.

MicroRNA-204-5p targets SOX11 to regulate the inflammatory response in spinal cord injury.

The purpose of this study was to investigate whether microRNA-204-5p can regulate the inflammatory response of spinal cord injury (SCI) by targeting SOX11. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of microRNA-204-5p in patients with SCI. The mouse SCI model was established to detect the recovery of the grip strength of the upper and lower limbs. Then, the expression of microRNA-204-5p in these mice with SCI was detected by qRT-PCR, and the levels of the inflammatory factors Toll-like receptor 4 (TLR4) and iNOS were examined by Western blot. Subsequently, microRNA- 204-5p was overexpressed in the mouse SCI model using lentivirus, and the changes in mouse grip strength and the inflammatory factor levels were observed. SOX11 was then searched as the target gene of microRNA-204-5p through bioinformatics analysis, and its expression in patients or mice with SCI was examined using qRT-PCR. SOX11 expression was again detected after the overexpression or knockdown of microRNA-204-5p in cells. The binding of microRNA-204-5p to SOX11 was verified by dual-luciferase reporting assay. After microRNA-204-5p and SOX11 were co-overexpressed in cells, the levels of TLR4 and iNOS were analyzed. Furthermore, the changes in the grip strength were observed in mice with SCI after simultaneous up-regulation of microRNA-204-5p and SOX11. Micro-204-5p level was conspicuously decreased in the population with SCI. And the SCI mouse model showed that the upper and lower limb strength conspicuously decreased and began to recover after 7 days. During the seven days, microRNA-204-5p level in the SCI mice decreased with time, while the levels of the inflammatory cytokines TLR4 and iNOS conspicuously increased. After microRNA-204-5p was overexpressed in SCI mice, their upper and lower limb strength was conspicuously restored, while the levels of TLR4 and iNOS were also remarkably decreased. The bioinformatics analysis revealed that there exist some binding sites between microRNA-204-5p and SOX11, and we found that SOX11 expression was conspicuously enhanced in the plasma of the SCI patients. Meanwhile, the SOX11 level in SCI mice was also conspicuously increased, and it was time-dependent. The expression of SOX11 was decreased after the upregulation of microRNA-204-5p, while the opposite result was observed after the downregulation of microRNA-204-5p. In addition, the result of the dual-luciferase reporter gene assay revealed that microRNA-204-5p could bind to SOX11 in a targeted manner. Meanwhile, the up-regulation of SOX11 was partially relieved by the inhibitory effect of microRNA-204-5p on TLR4 and iNOS. Moreover, the simultaneous overexpression of SOX11 and microRNA-204-5p partially reversed the impact of the up-regulated microRNA-204-5p alone on the recovery of the upper and lower limb strength in SCI mice. The low expression of microRNA-204-5p in patients with SCI can affect the levels of the inflammatory cytokines TLR4 and iNOS and improve SCI by targeting SOX11.

Neuregulin-1 Fosters Supportive Interactions between Microglia and Neural Stem/Progenitor Cells.

Microglia play diverse roles in homeostasis and pathology of the central nervous system (CNS). Their response to injury or insult is critical for initiating neuroinflammation and tissue damage as well as resolution of inflammation and wound healing. Changes to the microenvironment of microglia appear to be a key determinant of their phenotype and their role in the endogenous repair process in the injured or diseased CNS. Our recent findings have identified a positive role for neuregulin-1 (Nrg-1) in regulating immune response in spinal cord injury and focal demyelinating lesions. We show that increasing the tissue availability of Nrg-1 after injury can promote endogenous repair by modulating neuroinflammation. In the present study, we sought to elucidate the specific role of Nrg-1 in regulating microglial activity and more importantly their influence on the behavior of neural stem/progenitor cells (NPCs). Using injury-relevant in vitro systems, we demonstrate that Nrg-1 attenuates the expression of proinflammatory mediators in activated microglia. Moreover, we provide novel evidence that availability of Nrg-1 can restore the otherwise suppressed phagocytic ability of proinflammatory microglia. Interestingly, the presence of Nrg-1 in the microenvironment of proinflammatory microglia mitigates their inhibitory effects on NPC proliferation. Nrg-1 treated proinflammatory microglia also augment mobilization of NPCs, while they had no influence on their suppressive effects on NPC differentiation. Mechanistically, we show that Nrg-1 enhances the interactions of proinflammatory microglia and NPCs, at least in part, through reduction of TNF-α expression in microglia. These findings provide new insights into the endogenous regulation of microglia-NPC interactions and identify new potential targets for optimizing this important crosstalk during the regenerative process after CNS injury and neuroinflammatory conditions.

Over-expressed miR-27a-3p inhibits inflammatory response to spinal cord injury by decreasing TLR4.

We investigate whether microRNA-27a-3p (miR-27a-3p) can inhibit the inflammatory response of spinal cord injury by negatively regulating toll-like receptor 4 (TLR4). The quantitative Real-time polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-27a-3p and TLR4 in serum samples from patients with spinal cord injury and in hydrogen peroxide-treated C8-B4 and C8-D1A cells. Dual luciferase reporter assays were used to detect targeted binding of TLR4 to miR-27a-3p. The protein expression of miR-27a-3p and TLR4 and the two inflammatory factors, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), were all detected by Western blot. TLR4 expression was elevated and miR-27a-3p was decreased in serum samples from patients with spinal cord injury and in hydrogen peroxide-treated C8-D1A and C8-B4 cells. Dual luciferase reporter assays results demonstrated that miR-27a-3p can bind to TLR4. Up-regulation of miR-27a-3p can decrease the expression of TNF-α and IL-6 and can also reduce TLR4 expression. After overexpression of TLR4, the expression of TNF-α and IL-6 were increased. miR-27a-3p can inhibit the inflammatory response of spinal cord injury by negatively regulating TLR4.

Biochemical events related to glial response in spinal cord injury

Introducción. La lesión de la médula espinal (LME) es un evento devastador con implicaciones físicas, psicológicas y socioeconómicas. En el tejido cercano a la lesión se instauran cambios morfofisiológicos que determinan la recuperación funcional del segmento medular y de los órganos efectores dependientes de los tractos axonales lesionados.Objetivo. Describir los eventos bioquímicos secuenciales más relevantes de la respuesta de las células gliales posterior a la LME.Materiales y métodos. Se realizó una búsqueda de publicaciones científicas de los últimos 18 años en las bases de datos PubMed y ScienceDirect, bajo los términos en inglés spinal cord injury (SCI), SCI pathophysiology, SCI inflammation, microglia in SCI, glial scar y chondroitin sulfate proteoglycans (CSPG).Resultados. Los procesos fisiopatológicos que se producen después de la LME determinan la recuperación neurológica de los pacientes. La activación de las células gliales juega un papel importante, ya que promueve la producción de moléculas bioactivas y la formación de barreras físicas que inhiben la regeneración neural.Conclusión. El conocimiento de los cambios neurobiológicos ocurridos tras la LME permite una mayor comprensión de la fisiopatología y favorece la búsqueda de nuevas alternativas terapéuticas que limiten la progresión de la lesión primaria y que minimicen el daño secundario responsable de la disfunción neurológica.

Immunomodulation as a neuroprotective strategy after spinal cord injury.

The study was supported by Premios Santa Casa Neurociencias-Prize Meloe Castro for Spinal Cord Injury Research; Portuguese Foundation for Science and Technology (Financiado no ambito do Projecto 3599-Promover a Producao Cientifica e Desenvolvimento Tecnologico e a Constituicao de Redes Tematicas (3599-PPCDT), project: PTDC/DTP-FTO/5109/2014; Post-Doctoral fellowship-SFRH/BPD/97701/2013-to N.A. Silva; IF Development Grant to A. J. Salgado).

Electric field stimulation protects injured spinal cord from secondary inflammatory response in rats.

To investigate acute beneficial effects of electrical field stimulation (EFS) on secondary inflammatory response in spinal cord injury (SCI) rats. Sprague-Dawley (SD) rats were divided into three groups,sham group rats received laminectomy only, control group rats were subjected to SCI only, and EFS group rats received EFS immediately after the injury. During the 30-min-stimulation, the injury potential modulated to 0 ± 0.5 mV by EFS. At 12h, 24h and 48h after the surgery, the rats in each group were sacrificed. Immunofluorescence staining for macrophage marker (ED-1), the tautomerase activity of macrophage inhibitory factor (MIF) assay and real-time PCR analysis for interleukin-1β (IL-1β) and matrix metalloproteinase-9 (MMP-9) were performed. Compared to the rats in control group, the rats treated with EFS presented less ED-1 positive cells 12h (P <; 0.05), 24h (P <; 0.01) and 48h (P <; 0.05) after the surgery and showed a lower MIF tautomerase activity 12h (P <; 0.01), 24h (P <; 0.01) and 48h (P <; 0.01) after the surgery. Moreover, EFS significantly decreased the mRNA levels of IL-β (P <; 0.05) and MMP-9 at 48h (P <; 0.01) after the injury. EFS could attenuate secondary inflammatory response of injured spinal cord shortly after SCI, and EFS treatment could be a candidate for SCI therapy.

Neuregulin-1: a novel regulator of glial response in spinal cord injury

Neuregulin-1: a novel regulator of glial response in spinal cord injury

Histamine promotes locomotion recovery after spinal cord hemisection via inhibiting astrocytic scar formation.

This study investigated whether histamine could play a protective role in pathophysiological response of spinal cord injury (SCI) and regulate the glial scar formation. Functional assessment and histological analyses were performed to investigate the effect of histamine after SCI. Histidine decarboxylase knockout (HDC(-/-)) mice were used to confirm the action of histamine. Selective antagonists for H1 and H2 receptors were utilized in vivo and in vitro to verify the functional properties of histamine on astrogliosis. The local administration of histamine significantly attenuated the tissue damage and glial scar formation after SCI. In particular, the astrogliosis and neurocan expression found around the lesion were significantly suppressed by histamine. Immunofluorescent staining for neurofilament showed that histamine promoted axonal growth across the glial scar. The HDC(-/-) mice, lacking in endogenous histamine, showed lower behavior score, increased lesion size and astrogliosis, as compared with the wild types. The effect of histamine on locomotor recovery and reactive astrogliosis is reversed by H1 receptor antagonist but not H2 receptor antagonist. Our results indicate that histamine significantly improved the chronic locomotor recovery via attenuating astrogliosis after SCI by stimulating histamine H1 receptor. This study highlights a therapeutic potential of histamine and its related drugs for SCI.

Editorial Note on: Respiratory CO2 response in acute cervical spinal cord injury (CO2 response in spinal cord injury)

Editorial Note on: Respiratory CO 2 response in acute cervical spinal cord injury (CO 2 response in spinal cord injury)

Respiratory CO2 response in acute cervical spinal cord injury (CO2 response in spinal cord injury)

Retrospective study. The objective of this study was to compare the CO₂ response of acute tetraplegic cervical spinal cord injury (SCI) patients undergoing mechanical ventilation with a control group of critically ill patients ready for weaning of mechanical ventilation and successfully extubated. This study was conducted at the intensive care unit of a University Hospital in Mallorca, Spain. CO₂ response was studied in 12 acute tetraplegic cervical SCI patients at the C4-C7 level and 22 control patients. The control group patients were consecutively selected from a database of patients with mechanical ventilation and who were successfully extubated after a CO₂ response test. To increase the CO₂ , we used the method of re-inhalation of expired air, and we evaluated the hypercapnic ventilatory response, the change in minute ventilation induced by the increase of partial pressure of arterial carbon dioxide (PaCO₂ ), which measures the whole respiratory system (metabolic control, neuromuscular or ventilatory apparatus), and the hypercapnic drive response, the change in the airway occlusion pressure at 100 ms induced by the increase in PaCO2, which measures the chemosensitivity of the respiratory center. Cervical SCI patients were younger than the control group patients (26±7 and 62±12 years, respectively; P<0.001). Mean values of the hypercapnic ventilatory response in cervical SCI and control groups were 0.52±0.31 and 0.64±0.33 l min(-1) per mm Hg (P=0.40), respectively, and the hypercapnic drive response was 0.24±0.16 and 0.48±0.23 cm H₂O per mm Hg (P=0.001), respectively. Acute tetraplegic cervical SCI patients had reduced hypercapnic drive response that may contribute to the difficult weaning, without reduction in hypercapnic ventilatory response.