scholarly journals Acute and non-resolving inflammation associate with oxidative injury after human spinal cord injury

Brain ◽  
2020 ◽  
Author(s):  
Tobias Zrzavy ◽  
Carmen Schwaiger ◽  
Isabella Wimmer ◽  
Thomas Berger ◽  
Jan Bauer ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Damage ◽  
Tissue Injury ◽  
Neuronal Cell ◽  
Neuronal Cell Body ◽  
Traumatic Spinal Cord Injury ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Lesion Core

Abstract Traumatic spinal cord injury is a devastating insult followed by progressive cord atrophy and neurodegeneration. Dysregulated or non-resolving inflammatory processes can disturb neuronal homeostasis and drive neurodegeneration. Here, we provide an in-depth characterization of innate and adaptive inflammatory responses as well as oxidative tissue injury in human traumatic spinal cord injury lesions compared to non-traumatic control cords. In the lesion core, microglia were rapidly lost while intermediate (co-expressing pro- as well as anti-inflammatory molecules) blood-borne macrophages dominated. In contrast, in the surrounding rim, TMEM119+ microglia numbers were maintained through local proliferation and demonstrated a predominantly pro-inflammatory phenotype. Lymphocyte numbers were low and mainly consisted of CD8+ T cells. Only in a subpopulation of patients, CD138+/IgG+ plasma cells were detected, which could serve as candidate cellular sources for a developing humoral immunity. Oxidative neuronal cell body and axonal injury was visualized by intracellular accumulation of amyloid precursor protein (APP) and oxidized phospholipids (e06) and occurred early within the lesion core and declined over time. In contrast, within the surrounding rim, pronounced APP+/e06+ axon-dendritic injury of neurons was detected, which remained significantly elevated up to months/years, thus providing mechanistic evidence for ongoing neuronal damage long after initial trauma. Dynamic and sustained neurotoxicity after human spinal cord injury might be a substantial contributor to (i) an impaired response to rehabilitation; (ii) overall failure of recovery; or (iii) late loss of recovered function (neuro-worsening/degeneration).

scholarly journals The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Shmma Quraishe ◽  
Lindsey H. Forbes ◽  
Melissa R. Andrews
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nervous System ◽  
Axonal Regeneration ◽  
Neuronal Cell ◽  
Developmental State ◽  
Neuronal Cell Body ◽  
Mature Adult ◽  
Cord Injury ◽  
Extracellular Environment

The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury.

scholarly journals For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Sandra Zivkovic ◽  
Maryam Ayazi ◽  
Grace Hammel ◽  
Yi Ren
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Innate Immune System ◽  
Tissue Injury ◽  
Innate Immune ◽  
Traumatic Spinal Cord Injury ◽  
Injured Spinal Cord ◽  
Cord Injury ◽  
Molecular Patterns

Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.

scholarly journals MicroRNA-135a-5p reduces P2X7-dependent rise in intracellular calcium and protects against excitotoxicity

2019 ◽  
Author(s):  
David Reigada Prado ◽  
Andrés Ángel Calderón-García ◽  
Manuel Soto-Catalán ◽  
Manuel Nieto-Diaz ◽  
Teresa Muñoz-Galdeano ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Intracellular Calcium ◽  
Calcium Concentration ◽  
Neuronal Cell ◽  
Intracellular Calcium Concentration ◽  
Tissue Loss ◽  
Traumatic Spinal Cord Injury ◽  
Cord Injury ◽  
Excitotoxic Cell Death

Excitotoxic cell death due to the massive release of glutamate and ATP contributes to the secondary extension of cellular and tissue loss following traumatic spinal cord injury (SCI). Evidence from blockage experiments suggests that overexpression and activation of purinergic receptors, especially P2X7, causes excitotoxicity in neurodegenerative diseases and traumatisms of the central nervous system. We hypothesize that the downregulation of specific miRNAs after the SCI contributes to the overexpression of P2X7 and that restorative strategies can be used to reduce excitotoxic response. In the present study, we have employed bioinformatic analyses to identify microRNAs whose dowregulation following SCI can be responsible for P2X7 overexpression and excitotoxic activity. Additional luciferase assays validated microRNA-135a-5p (miR-135a) as a posttranscriptional modulator of P2X7. Moreover, gene expression analysis in spinal cord samples from a rat SCI model confirmed that the decrease in miR-135a expression correlates with P2X7 overexpression after injury. Transfection of cultures of Neuro-2a neuronal cell line with a miR-135a inhibitory sequences (antagomiR-135a), simulating the reduction of miR-135a observed after SCI, resulted in the increase of P2X7 expression and the subsequent ATP-dependent rise in intracellular calcium concentration. Conversely, a restorative strategy employing miR-135a mimics reduced P2X7expression attenuating the increase in intracellular calcium concentration that depends on this receptor and protecting cells from excitotoxic death. Therefore, we conclude that miR-135a is a potential therapeutic target for SCI and that restoration of its expression may reduce the deleterious effects of ATP-dependent excitotoxicity induced after a traumatic spinal cord injury.

Neurological Recovery in Traumatic Spinal Cord Injury Patient with Delayed Surgical Intervention

2018 ◽  
Vol 1 (2) ◽  
pp. 34
Author(s):  
Mochamad Targib Alatas
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Surgical Intervention ◽  
Case Series ◽  
Spinal Cord Injury Patient ◽  
Traumatic Spinal Cord Injury ◽  
Best Interest ◽  
Score Improvement ◽  
Cord Injury ◽  
Injury Patient

Early surgical treatment for traumatic spinal cord injury (SCI) patients has been proven to yield better improvement on neurological state, and widely practiced among surgeons in this field. However, it is not always affordable in every clinical setting. It is undeniable that surgery for chronic SCI has more challenges as the malunion of vertebral bones might have initiated, thus requires more complex operating techniques. In this case series, we report 7 patients with traumatic SCI whose surgical intervention is delayed due to several reasons. Initial motoric scores vary from 0 to 3, all have their interval periods supervised between outpatient clinic visits. On follow up they demonstrate significant neurological development defined by at least 2 grades motoric score improvement. Physical rehabilitation also began before surgery was conducted. These results should encourage surgeons to keep striving for the patient’s best interest, even when the injury has taken place weeks or even months before surgery is feasible because clinical improvement for these patients is not impossible. 

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