Pathophysiology Of Spinal Cord Injury Research Articles

The effect of periaqueductal gray's metabotropic glutamate receptor subtype 8 activation on locomotor function following spinal cord injury.

Background and aims The pathophysiology of spinal cord injury is very complex. One of the debilitating aspects of spinal cord injury in addition to pain is a defect in motor function below the lesion surface. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, on animal's locomotor functions in a model of compression spinal cord injury. Methods We used a contusion method (T6-T8) for induction of spinal cord injury. Male Wistar rats were randomly assigned to five equal groups (n = 10 per group). Clips compression injury model was used to induce spinal cord injury. Three weeks post injury DCPG, siRNA (small interfering Ribonucleic Acid) and normal saline (vehicle) were administered intra-ventrolaterally to the periaqueductal gray (PAG) region. Motor function, were assessed through BBB (Basso, Beattie, and Bresnahan Locomotor Rating Scale) and ladder walking test. In addition, the effects of DCPG on axonal regeneration in corticospinal tract were evaluated. Results We found that DCPG could improve motor function and axonal regeneration in corticospinal tract when compared to siRNA group. Conclusions The results revealed that activation of mGluR8 in PAG is capable to improve motor function and of axonal regeneration due to the inhibitory effect on glutamate transmission on the spinal cord surface and also the elimination of the deleterious effect of glutamate on the regeneration of the injured area as an excitatory neurotransmitter. Implications Our findings in this study showed that, more attention should be paid to glutamate and its receptors in spinal cord injury studies, whether at the spinal or cerebral level, especially in the field of motor function after spinal cord injury.

Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury

BackgroundA sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism.MethodsThe SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, western blotting, and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro.ResultsIn this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons.ConclusionsOur study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI and suggests that its inhibition may be a new treatment strategy for this traumatic condition.

The repair and autophagy mechanisms of hypoxia-regulated bFGF-modified primary embryonic neural stem cells in spinal cord injury.

There is no effective strategy for the treatment of spinal cord injury (SCI), a devastating condition characterized by severe hypoxia and ischemic insults. In this study, we investigated the histology and pathophysiology of the SCI milieu in a rat model and found that areas of hypoxia were unevenly interspersed in compressed SCI. With this new knowledge, we generated embryonic neural stem cells (NSCs) expressing basic fibroblast growth factor (bFGF) under the regulation of five hypoxia‐responsive elements (5HRE) using a lentiviral vector (LV‐5HRE‐bFGF‐NSCs) to specifically target these hypoxic loci. SCI models treated with bFGF expressed by the LV‐5HRE‐bFGF‐NSCs viral vector demonstrated improved recovery, increased neuronal survival, and inhibited autophagy in spinal cord lesions in the rat model due to the reversal of hypoxic conditions at day 42 after injury. Furthermore, improved functional restoration of SCI with neuron regeneration was achieved in vivo, accompanied by glial scar inhibition and the evidence of axon regeneration across the scar boundary. This is the first study to illustrate the presence of hypoxic clusters throughout the injury site of compressed SCI and the first to show that the transplantation of LV‐5HRE‐bFGF‐NSCs to target this hypoxic microenvironment enhanced the recovery of neurological function after SCI in rats; LV‐5HRE‐bFGF‐NSCs may therefore be a good candidate to evaluate cellular SCI therapy in humans.

Non-coding RNAs as therapeutic targets in spinal cord injury

Spinal cord injury (SCI) may be followed by persistent motor dysfunction and somatosensory disturbances that negatively influences the quality of life of patients and creates a significant economic burden. Analysis of secondary biological processes associated with changes in genetic expression is becoming increasingly important every day in understanding the pathophysiology of spinal cord injury. The results of international sequencing of the human genome were analyzed in 2004. These data revealed about 20,000 protein-coding genes covering near 2% of the total genomic sequence. The vast majority of gene transcripts are actually characterized as non-coding RNAs (ncRNAs). These RNA clusters do not encode functional proteins and ensure post-transcriptional regulation of gene expression. The clusters may be small (approximately 20 nucleotides) known as miRNAs or the transcripts can enroll over 200 nucleotides defined as long non-coding RNAs (lncRNAs). Some modern studies describe transient expression of microRNA in case of spinal cord injury. These RNAs are associated with inflammation and apoptosis, functional recovery and regeneration. Large-scale genomic analysis has demonstrated the existence of multiple lncRNAs whose expression is associated with some processes of spinal cord injury. lncRNA can be divided into two categories depending on the position in relation to the coding genes: intergenic and intragenic. Intergenic lncRNAs is currently the most studied class. Intragenic lncRNAs can be subdivided depending on the overlap of the coding genes (antisense, intron, etc.). According to recent studies, long non-coding RNAs are abundantly present in the tissues of central nervous system and may be crucial in the pathogenesis of certain diseases of nervous system. At the cellular level, it has been shown that lncRNAs regulate the expression of protein-coding RNAs. Moreover, these molecules are involved into such processes as neuronal death, demyelination and glia activation. This review is devoted to the role of ncRNAs in the pathogenesis of spinal cord injury and their potential use as targets for the treatment of consequences of spinal cord injury.

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination.

Spinal cord injury (SCI) is a devastating condition that may cause permanent functional loss below the level of injury, including paralysis and loss of bladder, bowel, and sexual function. Patients are rarely treated immediately, and this delay is associated with tissue loss and scar formation that can make regeneration at chronic time points more challenging. Herein, we investigated regeneration using a poly(lactide-co-glycolide) multichannel bridge implanted into a chronic SCI following surgical resection of necrotic tissue. We characterized the dynamic injury response and noted that scar formation decreased at 4 and 8 weeks postinjury (wpi), yet macrophage infiltration increased between 4 and 8 wpi. Subsequently, the scar tissue was resected and bridges were implanted at 4 and 8 wpi. We observed robust axon growth into the bridge and remyelination at 6 months after initial injury. Axon densities were increased for 8 week bridge implantation relative to 4 week bridge implantation, whereas greater myelination, particularly by Schwann cells, was observed with 4 week bridge implantation. The process of bridge implantation did not significantly decrease the postinjury function. Collectively, this chronic model follows the pathophysiology of human SCI, and bridge implantation allows for clear demarcation of the regenerated tissue. These data demonstrate that bridge implantation into chronic SCI supports regeneration and provides a platform to investigate strategies to buttress and expand regeneration of neural tissue at chronic time points.

Short-term inhibition of fibrinolytic system restores locomotor function after spinal cord injury in mice

Spinal cord injury (SCI) is caused by an initial mechanical insult followed by a series of deleterious events that promote the progressive damage of affected tissues. Fibrinolysis, the process by which plasmin degrades cross-linked fibrin clots, has numerous functions in the central nervous system. However, the roles of the fibrinolytic system in SCI pathophysiology remain unknown. We investigated the roles of fibrinolysis in SCI, and explored therapeutic applications targeting fibrinolysis. Plasminogen-deficient (Plg−/−) mice exhibited significantly improved locomotor function in the early phase of SCI (the first 7 days post injury), with significant inhibition of bleeding and vascular permeability, but failed to demonstrate conclusive functional recovery. Consistent with these findings, the short-term administration of tranexamic acid (TXA) in wild-type mice over the first 3 days post injury significantly improved locomotor function after SCI, whereas prolonged TXA administration did not. Prolonged TXA administration resulted in significantly lower levels of matrix metalloproteinase activities in the spinal cord, suggesting that inhibition of the fibrinolytic system impaired tissue remodeling. Our results indicate that the fibrinolytic system has time-dependent biphasic actions following SCI. The temporally optimised modulation of fibrinolytic activity may thus be a novel therapeutic strategy to improve functional outcomes after SCI.

Regenerative Therapies for Spinal Cord Injury.

Spinal cord injury (SCI) is a serious problem that primarily affects younger and middle-aged adults at its onset. To date, no effective regenerative treatment has been developed. Over the last decade, researchers have made significant advances in stem cell technology, biomaterials, nanotechnology, and immune engineering, which may be applied as regenerative therapies for the spinal cord. Although the results of clinical trials using specific cell-based therapies have proven safe, their efficacy has not yet been demonstrated. The pathophysiology of SCI is multifaceted, complex and yet to be fully understood. Thus, combinatorial therapies that simultaneously leverage multiple approaches will likely be required to achieve satisfactory outcomes. Although combinations of biomaterials with pharmacologic agents or cells have been explored, few studies have combined these modalities in a systematic way. For most strategies, clinical translation will be facilitated by the use of minimally invasive therapies, which are the focus of this review. In addition, this review discusses previously explored therapies designed to promote neuroregeneration and neuroprotection after SCI, while highlighting present challenges and future directions. Impact Statement To date there are no effective treatments that can regenerate the spinal cord after injury. Although there have been significant preclinical advances in bioengineering and regenerative medicine over the last decade, these have not translated into effective clinical therapies for spinal cord injury. This review focuses on minimally invasive therapies, providing extensive background as well as updates on recent technological developments and current clinical trials. This review is a comprehensive resource for researchers working towards regenerative therapies for spinal cord injury that will help guide future innovation.

Macrophage MSR1 Promotes the Formation of Foamy Macrophage and Neuronal Apoptosis after Spinal Cord Injury

Background: A sustained inflammatory response following spinal cord injury (SCI) contributes to neuronal damage, inhibiting functional recovery. Macrophages, the major participants in the inflammatory response, transform into foamy macrophages after phagocytosing myelin debris, subsequently releasing inflammatory factors and amplifying the secondary injury. Here, we assessed the effect of macrophage scavenger receptor 1 (MSR1) in phagocytosis of myelin debris after SCI and explained its possible mechanism. Methods: The SCI model was employed to determine the critical role of MSR1 in phagocytosis of myelin debris in vivo. The potential functions and mechanisms of MSR1 were explored using qPCR, Western blotting and immunofluorescence after treating macrophages and RAW264.7 with myelin debris in vitro. Findings: In this study, we found improved recovery from traumatic SCI in MSR1-knockout mice over that in MSR1 wild-type mice. Furthermore, MSR1 promoted the phagocytosis of myelin debris and the formation of foamy macrophage, leading to pro-inflammatory polarization in vitro and in vivo. Mechanistically, in the presence of myelin debris, MSR1-mediated NF-κB signaling pathway contributed to the release of inflammatory mediators and subsequently the apoptosis of neurons. Interpretation: Our study elucidates a previously unrecognized role of MSR1 in the pathophysiology of SCI, and suggests that its inhibition may be a new treatment strategy for this traumatic condition. Funding Statement: This study was supported by grants from the National Natural Science Foundation of China (81772351, 81520108018, 81472080, 81772352, and 81401800), the Jiangsu Committee of Science and Technology–Social Development Plan (BE2017755), the Jiangsu Six Talents Peak (WSN-011), the Nanjing Committee of Science and Technology (201505005), Medical Science and technology development Foundation from Nanjing Department of Health (YKK17060), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (SJCX18_0430). Declaration of Interests: The authors declare that they have no conflict of interest. Ethics Approval Statement: The animal protocols were approved by the Animal Committee of the First Affiliated Hospital of Nanjing Medical University.

Early Management of Acute Spinal Cord Injury-Part I: Initial Injury to Surgery.

Acute spinal cord injury is a devastating event associated with substantial morbidity worldwide. The pathophysiology of spinal cord injury involves the initial mechanical trauma and the subsequent inflammatory response, which may worsen the severity of neurologic dysfunction. Interventions have been studied to reduce the extent of primary injury to the spinal cord through preventive measures and to mitigate secondary insult through early specialized care. Management, therefore, is multifold, interdisciplinary, and begins immediately at the time of injury. It includes the trauma triage, acute management of the circulatory and respiratory systems, and definitive treatment, mainly with surgical decompression and stabilization.

Prospects of siRNA cocktails as tools for modifying multiple gene targets in the injured spinal cord.

Gene silencing through RNA interference (RNAi) has been touted as a boon for identifying potential therapies for difficult-to-treat pathologies. In this regard, siRNA-mediated gene silencing for tackling the multifaceted pathophysiology of spinal cord injury seemed promising. The genes caspase 3 and sarm1 were targeted in the present study, using siRNAs in a rodent model of spinal cord injury, as the feasibility of concomitant silencing of more than one gene had not been previously attempted. The results indicated meager benefits in terms of functional recovery and tissue preservation. Interestingly, differential transfection efficiencies due to the heterogeneous nature of cells in the spinal cord along with variability in efficacy based on time of intervention affected the reproducibility of this approach. Complex gene interactions and inadequacies in molecular evaluation strategies further complicated the interpretation of the outcome. If these glitches are resolved through further research, gene therapy in general and RNAi, in particular, may become a mainstay approach for treating contusion spinal cord injury.Impact statementGene therapy has reached the level of clinical trials. However, safety and efficacy are yet to be confirmed. The present study tested the prospects of gene silencing using siRNAs in a rat model of spinal cord injury. Some noteworthy observations include the effective and long-lasting silencing effects of siRNAs, inhibition of one gene's expression resulting in silencing of multiple genes in associated pathways, possibility of targeting more than one gene through siRNA cocktails, and differential gene silencing effects based on temporal changes in their expression patterns. It is argued that differential uptake of siRNAs by cells as observed and limitations in the analysis methods available can skew interpretations. Thus, this study may serve as a cautionary tale indicating that gene silencing using siRNAs for spinal cord injury can be a potential therapy, but practical issues are to be addressed in order to ensure consistency and safety.

Modern Medical Management of Spinal Cord Injury.

Spinal cord injury (SCI) shows an incidence of 10.4-83 cases/million/year globally and remains a significant source of morbidity and cost to society. Despite greater understanding of the pathophysiology of SCI, neuroprotective and regenerative approaches to treatment have had limited clinical utility to date. Here, we review the key components of supportive care that are thus the mainstay of therapy and that have improved outcomes for victims of acute SCI in recent decades. Current management strategies for acute SCI involve early surgical decompression and fixation, the use of vasopressor medications for mean arterial blood pressure (MAP) augmentation to improve spinal cord perfusion, and corticosteroids. We highlight recent literature supporting the role of norepinephrine in acute SCI management and also an emerging neurocritical care strategy that seeks to optimize spinal cord perfusion pressure with the assistance of invasive monitoring. This review will highlight key pathophysiologic principles and targets for current acute clinical treatments in SCI, which include early surgical decompression, MAP augmentation, and corticosteroids. We discuss anticipated future research in these areas and focus on potential risks inherent to these treatments.

CPLA2 activation contributes to lysosomal defects leading to impairment of autophagy after spinal cord injury

The autophagy–lysosomal pathway plays an essential role in cellular homeostasis as well as a protective function against a variety of diseases including neurodegeneration. Conversely, inhibition of autophagy, for example due to lysosomal dysfunction, can lead to pathological accumulation of dysfunctional autophagosomes and consequent neuronal cell death. We previously reported that autophagy is inhibited and contributes to neuronal cell death following spinal cord injury (SCI). In this study, we examined lysosomal function and explored the mechanism of lysosomal defects following SCI. Our data demonstrated that expression levels and processing of the lysosomal enzyme cathepsin D (CTSD) are decreased by 2 h after SCI. Enzymatic activity levels of CTSD and another lysosomal enzyme, N-acetyl-alpha-glucosaminidase, are both decreased 24 h post injury, indicating general lysosomal dysfunction. Subcellular fractionation and immunohistochemistry analysis demonstrated that this dysfunction is due to lysosomal membrane permeabilization and leakage of lysosomal contents into the cytosol. To directly assess extent and mechanisms of damage to lysosomal membranes, we performed mass spectrometry-based lipidomic analysis of lysosomes purified from SCI and control spinal cord. At 2 h post injury our data demonstrated increase in several classes of lysosophospholipids, the products of phospholipases (PLAs), as well as accumulation of PLA activators, ceramides. Phospholipase cPLA2, the main PLA species expressed in the CNS, has been previously implicated in mediation of secondary injury after SCI, but the mechanisms of its involvement remain unclear. Our data demonstrate that cPLA2 is activated within 2 h after SCI preferentially in the lysosomal fraction, where it colocalizes with lysosomal-associated membrane protein 2 in neurons. Inhibition of cPLA2 in vivo decreased lysosomal damage, restored autophagy flux, and reduced neuronal cell damage. Taken together our data implicate lysosomal defects in pathophysiology of SCI and for the first time indicate that cPLA2 activation leads to lysosomal damage causing neuronal autophagosome accumulation associated with neuronal cell death.

Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds.

Significant progress has been made in the treatment of spinal cord injury (SCI). Advances in post-trauma management and intensive rehabilitation have significantly improved the prognosis of SCI and converted what was once an “ailment not to be treated” into a survivable injury, but the cold hard fact is that we still do not have a validated method to improve the paralysis of SCI. The irreversible functional impairment of the injured spinal cord is caused by the disruption of neuronal transduction across the injury lesion, which is brought about by demyelination, axonal degeneration, and loss of synapses. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. The discovery of the regenerative capability of central nervous system neurons in the proper environment and the verification of neural stem cells in the spinal cord once incited hope that a cure for SCI was on the horizon. That hope was gradually replaced with mounting frustration when neuroprotective drugs, cell transplantation, and strategies to enhance remyelination, axonal regeneration, and neuronal plasticity demonstrated significant improvement in animal models of SCI but did not translate into a cure in human patients. However, recent advances in SCI research have greatly increased our understanding of the fundamental processes underlying SCI and fostered increasing optimism that these multiple treatment strategies are finally coming together to bring about a new era in which we will be able to propose encouraging therapies that will lead to appreciable improvements in SCI patients. In this review, we outline the pathophysiology of SCI that makes the spinal cord refractory to regeneration and discuss the research that has been done with cell replacement and biomaterial implantation strategies, both by itself and as a combined treatment. We will focus on the capacity of these strategies to facilitate the regeneration of neural connectivity necessary to achieve meaningful functional recovery after SCI.

Filling the Gap: Neural Stem Cells as A Promising Therapy for Spinal Cord Injury.

Spinal cord injury (SCI) can lead to severe motor, sensory and social impairments having a huge impact on patients’ lives. The complex and time-dependent SCI pathophysiology has been hampering the development of novel and effective therapies. Current treatment options include surgical interventions, to stabilize and decompress the spinal cord, and rehabilitative care, without providing a cure for these patients. Novel therapies have been developed targeting different stages during trauma. Among them, cell-based therapies hold great potential for tissue regeneration after injury. Neural stem cells (NSCs), which are multipotent cells with inherent differentiation capabilities committed to the neuronal lineage, are especially relevant to promote and reestablish the damaged neuronal spinal tracts. Several studies demonstrate the regenerative effects of NSCs in SCI after transplantation by providing neurotrophic support and restoring synaptic connectivity. Therefore, human clinical trials have already been launched to assess safety in SCI patients. Here, we review NSC-based experimental studies in a SCI context and how are they currently being translated into human clinical trials.

Differential Expression Profiles and Functional Predication of Circular Ribonucleic Acid in Traumatic Spinal Cord Injury of Rats.

Recent studies indicate that circular ribonucleic acids (circRNAs) are involved in a variety of human diseases. The roles of circRNAs in traumatic spinal cord injury (SCI) remain unknown, however. We performed RNA-seq to analyze the circRNA expression profile in rat spinal cord after SCI and to investigate the relevant mechanisms. In all, 150 circRNAs were significantly differentially expressed in rat spinal cord after SCI by a fold-change ≥2 and p value ≤0.05. Among these, 99 circRNAs were upregulated, while 51 were downregulated. Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway analyses, and circRNA/miocroRNA (miRNA) interaction networks were conducted to predict the potential roles of circRNAs in the process of SCI. In addition, the expression levels of six selected circRNAs were verified successfully by quantitative real-time polymerase chain reaction. Further study identified circRNA_07079 and circRNA_01282 as being associated with SCI, and they may participate in the pathophysiology of SCI through circRNA-targeted miRNA-messenger RNA axis. In summary, the results of our study revealed the expression profiles and potential functions of differentially expressed circRNAs in traumatic SCI in rats; this may provide new clues for studying the mechanisms underlying SCI and also present novel molecular targets for clinical therapy of SCI.

Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms

Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers. Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients. However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients. This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord. Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord. To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI. In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI. We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats.

The pathophysiology of spinal cord injury (SCI) involves primary injury and secondary injury. For the irreversibility of primary injury, therapies of SCI mainly focus on secondary injury, whereas inflammation is considered to be a major target for secondary injury; however the regulation of inflammation in SCI is unclear and targeted therapies are still lacking. In this study, we found that the expression of BRD4 was correlated with pro‐inflammatory cytokines after SCI in rats; in vitro study in microglia showed that BRD4 inhibition either by lentivirus or JQ1 may both suppress the MAPK and NF‐κB signalling pathways, which are the two major signalling pathways involved in inflammatory response in microglia. BRD4 inhibition by JQ1 not only blocked microglial M1 polarization, but also repressed the level of pro‐inflammatory cytokines in microglia in vitro and in vivo. Furthermore, BRD4 inhibition by JQ1 can improve functional recovery and structural disorder as well as reduce neuron loss in SCI rats. Overall, this study illustrates that microglial BRD4 level is increased after SCI and BRD4 inhibition is able to suppress M1 polarization and pro‐inflammatory cytokine production in microglia which ultimately promotes functional recovery after SCI.

MicroRNAs in contusion spinal cord injury: pathophysiology and clinical utility.

Spinal cord injury (SCI) in humans is a common central nervous system trauma. Pathophysiologically, SCI involves both primary and secondary damages. Therapeutically, targeting secondary damage including inflammation, neuropathic pain, apoptosis, demyelination, and glial reaction to promote functional benefits for SCI patients has long been considered a potential treatment strategy by neuroscientists and clinicians. As a type of small non-coding RNA, microRNAs (miRNAs) have been shown to play essential roles in the regulation of pathophysiologic processes of SCI and are considered to be an effective treatment method for SCI. Dysregulated expression of miRNAs is observed in SCI patients and animal models of SCI. Furthermore, miRNAs might also be used as biomarkers for diagnostic and prognostic purposes in SCI. Given contusion injury is the most clinically relevant type of SCI, this review mainly focuses on the role of miRNAs in the pathophysiology of contusion SCI and the putative utilization of miRNAs as diagnostic biomarkers and therapeutic targets for contusion SCI.

Biomarkers in Spinal Cord Injury: Prognostic Insights and Future Potentials.

Spinal Cord Injury (SCI) is a major challenge in Neurotrauma research. Complex pathophysiological processes take place immediately after the injury and later on as the chronic injury develops. Moreover, SCI is usually accompanied by traumatic injuries because the most common modality of injury is road traffic accidents and falls. Patients develop significant permanent neurological deficits that depend on the extent and the location of the injury itself and in time they develop further neurological and body changes that may risk their mere survival. In our review, we explored the recent updates with regards to SCI biomarkers. We observed two methods that may lead to the appearance of biomarkers for SCI. First, during the first few weeks following the injury the Blood Spinal Cord Barrier (BSCB) disruption that releases several neurologic structure components from the injured tissue. These components find their way to Cerebrospinal Fluid (CSF) and the systemic circulation. Also, as the injury develops several components of the pathological process are expressed or released such as in neuroinflammation, apoptosis, reactive oxygen species, and excitotoxicity sequences. Therefore, there is a growing interest in examining any correlations between these components and the degrees or the outcomes of the injury. Additionally, some of the candidate biomarkers are theorized to track the progressive changes of SCI which offers an insight on the patients' prognoses, potential-treatments-outcomes assessment, and monitoring the progression of the complications of chronic SCI such as Pressure Ulcers and urinary dysfunction. An extensive literature review was performed covering literature, published in English, until February 2018 using the Medline/PubMed database. Experimental and human studies were included and titles, PMID, publication year, authors, biomarkers studies, the method of validation, relationship to SCI pathophysiology, and concluded correlation were reported. Potential SCI biomarkers need further validation using clinical studies. The selection of the appropriate biomarker group should be made based on the stage of the injuries, the accompanying trauma and with regards to any surgical, or medical interference that might have been done. Additionally, we suggest testing multiple biomarkers related to the several pathological changes coinciding to offer a more precise prediction of the outcome.

Spinal Cord Protection for Thoracic Aortic Surgery: Bench to Bedside

This article summarizes the anatomically driven pathophysiology of spinal cord injury, the impact of ischemia reperfusion on the cellular level, current research in developing neuronal ischemic tolerance, and promotion of collateralization. It addresses neuroprotective strategies in modern clinical practice, current pharmacologic interventions, and continued challenges in the management of complex aortic disease. The pathophysiology of spinal cord injury includes disruption and recovery of collateral blood flow and the effects of malperfusion on the spinal cord. The optimal approach to spinal cord protection is to employ an integrated and protocolized set of strategies to simultaneously maximize spinal cord blood flow, improve ischemic tolerance, and promote collateralization. In the laboratory setting, investigation should continue to pursue a more granular understanding of ischemic injury and seek to translate protective therapies to clinical practice.