Current Knowledge of Microglia in Traumatic Spinal Cord Injury

Microglia are the resident immune cells in the central nervous system (CNS). After traumatic spinal cord injury (SCI), microglia undergo activation, proliferation, and changes in gene and protein expression and morphology, with detrimental and beneficial effects. Activated microglia cause secondary neuronal injury via the production of proinflammatory cytokines, reactive oxygen species, and proteases. However, activated microglia also promote neuronal repair through the secretion of anti-inflammatory growth factors and cytokines. Proinflammatory cytokines increase endothelial permeability, promote A1 astrocyte activation and axonal demyelination, and reduce neural stem/progenitor cells (NSPCs), leading to the exacerbation of neuronal injury. In contrast, anti-inflammatory factors facilitate angiogenesis, reduce reactive astrocytes, and promote axonal remyelination and the propagation of NSPCs, contributing to tissue repair and locomotor recovery. Due to its limited regenerative capacity, the CNS requires beneficial microglia for continuous protection against injury. Understanding and regulating microglial activation status are beneficial to reducing detrimental effects and promoting repair behaviors and to obtain more information on efficient therapies for traumatic SCI. This review discusses microglial activation and the differences between microglia and similar immune cells, microglial interactions with other cells in the spinal cord, and the progress in the development of therapies targeting microglia in SCI.

Enhancing Functional Recovery Through Intralesional Application of Extracellular Vesicles in a Rat Model of Traumatic Spinal Cord Injury

Local inflammation plays a pivotal role in the process of secondary damage after spinal cord injury. We recently reported that acute intravenous application of extracellular vesicles (EVs) secreted by human umbilical cord mesenchymal stromal cells dampens the induction of inflammatory processes following traumatic spinal cord injury. However, systemic application of EVs is associated with delayed delivery to the site of injury and the necessity for high doses to reach therapeutic levels locally. To resolve these two constraints, we injected EVs directly at the lesion site acutely after spinal cord injury. We report here that intralesional application of EVs resulted in a more robust improvement of motor recovery, assessed with the BBB score and sub-score, as compared to the intravenous delivery. Moreover, the intralesional application was more potent in reducing inflammation and scarring after spinal cord injury than intravenous administration. Hence, the development of EV-based therapy for spinal cord injury should aim at an early application of vesicles close to the lesion.

Hyperbaric oxygenation therapy in treatment of traumatic spinal cord injury: a pilot study

Spinal cord traumatic injury as resulting persistent movement and sensory disorders is one of the most disabling consequences of traumatic factor impact on the human body. Despite a large number of experimental and clinical studies aimed at developing methods for restoring lost functions, there is no acceptable solution to the problem. One of the promising areas in the treatment and rehabilitation of this category of patients is the use of hyperbaric oxygenation (HBO). Experimental models have shown that HBO has a neuroprotective effect in spinal cord injury, but the results of clinical application of the method are still controversial. Objective: to determine the effectiveness of HBO in the complex therapy of victims with traumatic spinal cord injury and the feasibility of further study of this area. Materials and Methods: Study design is a pilot observational retrospective “case – control”. The database of patients with spinal cord injury who were hospitalized at Romodanov Neurosurgery Institute in the period from 2010 to 2020 were used for the analysis. When selecting a control for each clinical case, the following factors were considered: gender, age, circumstances of injury, type of damage to the osteoligamentous apparatus, level of neurological deficit, degree of damage and compression of the spinal cord, time elapsed from the moment of injury to surgery. 28 "case ‒ control" pairs were analyzed. The main criterion for therapy effectiveness was the change in the functional class according to the ASIA scale. Results. Positive dynamics was registered in 57% of victims, including in the group of patients receiving HBO therapy - in 71%, in the control group - in 43%. HBO therapy in the postoperative period significantly affects the dynamics of regression of neurological disorders (p=0.0295). The odds ratio is 3.333 (95% confidence interval - 1.098‒10.116, p=0.0335). The calculation of the odds ratio, adjusted for additional analyzed factors, showed a more pronounced efficiency - 4.519 (95% confidence interval - 1.279‒15.962, p=0.0192). Conclusions. The obtained results indicate that usage of HBO as a method of complex therapy for traumatic spinal cord injury is promising for further study in order to determine the effectiveness of the method, the optimal timing of treatment initiation in the postoperative period and its duration.

Long-Term Survival and Causes of Death in Patients below the Age of 60 with Traumatic Spinal Cord Injury in Germany

To study the mortality, cause and risk indicators of death in German patients with traumatic spinal cord injury, patients with traumatic spinal cord injury admitted to Berufsgenossenschaftliches Trauma Hospital Hamburg between 1 January 1997 and 31 December 2018, aged between 16 and 60 with a minimal survival of one year after injury, were included. Further criteria were the absence of life-limiting comorbidities at the time of injury. 223 deceased patients with traumatic spinal cord injury were identified, investigated on and partly compared to the surviving subjects. We aimed to discover specific complications that were related to Spinal Cord Injury and responsible for a possibly limited life expectancy. Data collection was performed during in- and outpatient treatment. A statistical analysis was performed to compare groups. The post-injury life expectancy was 25.0 years with a significant correlation regarding the level of lesion and severity of injury. The leading causes of death were cardiovascular diseases and pneumonia. Bladder cancer was the most common fatal malignant tumor. The life expectancy of patients suffering from traumatic spinal cord injury is limited. The longer a patient survives after injury and the lower the level of lesion, the more likely an age-related cause of death becomes. Bladder cancer is significantly more frequent when compared to the overall distribution of tumor diseases in Germany.