scholarly journals Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury

2017 ◽  
Vol 12 (5) ◽  
pp. 702 ◽  
Author(s):  
Yinghui Zhong ◽  
RobertB Shultz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Secondary Injury ◽  
Traumatic Spinal Cord Injury ◽  
Injury Mechanisms ◽  
Cord Injury

Physiologic Modulators of Neural Injury After Brain and Spinal Cord Injury

2017 ◽  
Author(s):  
W. Dalton Dietrich
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Cell ◽  
Acute Injury ◽  
Secondary Injury ◽  
Edema Formation ◽  
Blood Brain Barrier Disruption ◽  
Injury Mechanisms ◽  
Cord Injury ◽  
Brain And Spinal Cord

Brain and spinal cord injury are leading causes of death and long-term disability, producing diverse burdens for the affected individuals, their families, and society. Such injuries, including traumatic brain injury, stroke, subarachnoid hemorrhage, and spinal cord injury, have common patterns of neuronal cell vulnerability that are associated with a complex cascade of pathologic processes that trigger the propagation of tissue damage beyond the acute injury. Secondary injury mechanisms, including oxidative stress, edema formation, changes in cerebral blood flow and vessel reactivity, metabolic and blood–brain barrier disruption, and neuroinflammation, are therefore important therapeutic targets. Several key physiological parameters require monitoring and intensive management during various phases of treatment to ameliorate secondary injury mechanisms and potentially protect against further neuronal injury. This chapter reviews the core physiological targets in the management of brain and spinal cord injury and relates them to secondary injury mechanisms and outcomes.

Why Do We Not Have a Drug to Treat Acute Spinal Cord Injury?

Neurotrauma ◽  
2018 ◽  
pp. 411-422
Author(s):  
James W. Geddes
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Spinal Cord Injury ◽  
Secondary Injury ◽  
Functional Deficits ◽  
Injury Mechanisms ◽  
Cord Injury ◽  
Contusion Injury ◽  
Weight Drop ◽  
Intraspinal Hemorrhage

More than 100 years ago, Alfred Reginald Allen developed the weight-drop model of graded, reproducible contusion injury to the dorsal spinal cord. Allen also introduced the concept of secondary injury mechanisms, hypothesizing that hemorrhage and elevated intraspinal pressure contribute to the destruction of the spinal cord and functional deficits. Our understanding of the secondary injury cascade has advanced tremendously over the past 100 years, with numerous therapeutic targets identified. Yet we lack an effective drug treatment for acute spinal cord injury. Reasons for the failure to translate promising preclinical findings to successful clinical trials include concerns regarding the quality of preclinical studies, including possible bias and inappropriate statistical analysis; questions regarding the suitability of animal models; and the complexity of secondary mechanisms following spinal cord injury. Perhaps, however, we have overlooked the targets identified by Allen, namely the intraspinal hemorrhage and elevations in intraspinal pressure.

scholarly journals Vascular mechanisms in the pathophysiology of human spinal cord injury

1997 ◽  
Vol 2 (1) ◽  
pp. E2
Author(s):  
Charles H. Tator ◽  
Izumi Koyanagi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
White Matter Lesions ◽  
Arterial System ◽  
Secondary Injury ◽  
Human Spinal Cord ◽  
Injury Mechanisms ◽  
Cord Injury

Vascular injury plays an important role in the primary and secondary injury mechanisms that cause damage to the acutely traumatized spinal cord. To understand the pathophysiology of human spinal cord injury, the authors investigated the vascular system in three uninjured human spinal cords using silicone rubber microangiography and analyzed the histological findings related to vascular injury in nine acutely traumatized human spinal cords obtained at autopsy. The interval from spinal cord injury to death ranged from 20 minutes to 9 months. The microangiograms of the uninjured human cervical cords demonstrated new information about the sulcal arterial system and the pial arteries. The centrifugal sulcal arterial system was found to supply all of the anterior gray matter, the anterior half of the posterior gray matter, approximately the inner half of the anterior and lateral white columns, and the anterior half of the posterior white columns. Traumatized spinal cord specimens in the acute stage (3-5 days postinjury) showed severe hemorrhages predominantly in the gray matter, but also in the white matter. The white matter surrounding the hemorrhagic gray matter showed a variety of lesions, including decreased staining, disrupted myelin, and axonal and periaxonal swelling. The white matter lesions extended far from the injury site, especially in the posterior columns. There was no evidence of complete occlusion of any of the larger arteries, including the anterior and posterior spinal arteries and the sulcal arteries. However, occluded intramedullary veins were identified in the degenerated posterior white columns. In the chronic stage (3-9 months postinjury), the injured segments showed major tissue loss with large cavitations, whereas both rostral and caudal remote sites showed well-demarcated necrotic areas indicative of infarction mainly in the posterior white columns. Obstruction of small intramedullary arteries and veins by the initial mechanical stress or secondary injury mechanisms most likely produced these extensive white matter lesions. Our studies implicate damage to the anterior sulcal arteries in causing the hemorrhagic necrosis and subsequent central myelomalacia at the injury site in acute spinal cord injury in humans.

scholarly journals Revascularization After Traumatic Spinal Cord Injury

2021 ◽  
Vol 12 ◽  
Author(s):  
Chun Yao ◽  
Xuemin Cao ◽  
Bin Yu
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Vessel ◽  
Vascular System ◽  
Mechanical Damage ◽  
Pathological Process ◽  
Secondary Injury ◽  
Traumatic Spinal Cord Injury ◽  
Physical Stimulation ◽  
Cord Injury

Traumatic spinal cord injury (SCI) is a complex pathological process. The initial mechanical damage is followed by a progressive secondary injury cascade. The injury ruptures the local microvasculature and disturbs blood-spinal cord barriers, exacerbating inflammation and tissue damage. Although endogenous angiogenesis is triggered, the new vessels are insufficient and often fail to function normally. Numerous blood vessel interventions, such as proangiogenic factor administration, gene modulation, cell transplantation, biomaterial implantation, and physical stimulation, have been applied as SCI treatments. Here, we briefly describe alterations and effects of the vascular system on local microenvironments after SCI. Therapies targeted at revascularization for SCI are also summarized.

Vascular mechanisms in the pathophysiology of human spinal cord injury

1997 ◽  
Vol 86 (3) ◽  
pp. 483-492 ◽  
Author(s):  
Charles H. Tator ◽  
Izumi Koyanagi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
White Matter Lesions ◽  
Arterial System ◽  
Secondary Injury ◽  
Human Spinal Cord ◽  
Injury Mechanisms ◽  
Cord Injury

✓ Vascular injury plays an important role in the primary and secondary injury mechanisms that cause damage to the acutely traumatized spinal cord. To understand the pathophysiology of human spinal cord injury, the authors investigated the vascular system in three uninjured human spinal cords using silicone rubber microangiography and analyzed the histological findings related to vascular injury in nine acutely traumatized human spinal cords obtained at autopsy. The interval from spinal cord injury to death ranged from 20 minutes to 9 months. The microangiograms of the uninjured human cervical cords demonstrated new information about the sulcal arterial system and the pial arteries. The centrifugal sulcal arterial system was found to supply all of the anterior gray matter, the anterior half of the posterior gray matter, approximately the inner half of the anterior and lateral white columns, and the anterior half of the posterior white columns. Traumatized spinal cord specimens in the acute stage (3–5 days postinjury) showed severe hemorrhages predominantly in the gray matter, but also in the white matter. The white matter surrounding the hemorrhagic gray matter showed a variety of lesions, including decreased staining, disrupted myelin, and axonal and periaxonal swelling. The white matter lesions extended far from the injury site, especially in the posterior columns. There was no evidence of complete occlusion of any of the larger arteries, including the anterior and posterior spinal arteries and the sulcal arteries. However, occluded intramedullary veins were identified in the degenerated posterior white columns. In the chronic stage (3–9 months postinjury), the injured segments showed major tissue loss with large cavitations, whereas both rostral and caudal remote sites showed well-demarcated necrotic areas indicative of infarction mainly in the posterior white columns. Obstruction of small intramedullary arteries and veins by the initial mechanical stress or secondary injury mechanisms most likely produced these extensive white matter lesions. Our studies implicate damage to the anterior sulcal arteries in causing the hemorrhagic necrosis and subsequent central myelomalacia at the injury site in acute spinal cord injury in humans.

scholarly journals SCING—Spinal Cord Injury Neuroprotection with Glyburide: a pilot, open-label, multicentre, prospective evaluation of oral glyburide in patients with acute traumatic spinal cord injury in the USA

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e031329 ◽  
Author(s):  
Amy Janelle Minnema ◽  
A Mehta ◽  
Warren W Boling ◽  
Jan Schwab ◽  
J Marc Simard ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Drug Administration ◽  
Transient Receptor Potential ◽  
Secondary Injury ◽  
Traumatic Spinal Cord Injury ◽  
Open Label ◽  
Transient Receptor Potential Melastatin ◽  
Cord Injury ◽  
Neuroprotective Strategy

IntroductionAcute traumatic spinal cord injury (tSCI) is a devastating neurological disorder with no pharmacological neuroprotective strategy proven effective to date. Progressive haemorrhagic necrosis (PHN) represents an increasingly well-characterised mechanism of secondary injury after tSCI that negatively impacts neurological outcomes following acute tSCI. Preclinical studies evaluating the use of the Food and Drug Administration-approved sulfonylurea receptor 1-transient receptor potential melastatin 4 channel blocker glyburide in rodent models have shown reduced secondary microhaemorrhage formation and the absence of capillary fragmentation, the pathological hallmark of PHN.Methods and analysisIn this initial phase multicentre open-label pilot study, we propose to enrol 10 patients with acute cervical tSCI to primarily assess the feasibility, and safety of receiving oral glyburide within 8 hours of injury. Secondary objectives include pharmacokinetics and preliminary evaluations on neurological recovery as well as blood and MRI-based injury biomarkers. Analysis will be performed using the descriptive and non-parametric statistics.Ethics and disseminationGlyburide has been shown as an effective neuroprotective agent in preclinical tSCI models and in the treatment of ischaemic stroke with the additional risk of a hypoglycaemic response. Given the ongoing secondary injury and the traumatic hyperglycaemic stress response seen in patients with tSCI, glyburide; thus, offers an appealing neuroprotective strategy to supplement standard of care treatment. The study protocol was approved by the Ohio State University Biomedical Institutional Review Board. The protocol was amended in February 2017 with changes related to study feasibility and patient recruitment. Specifically, the route of administration was changed to the oral form to allow for streamlined and rapid drug administration, and the injury-to-drug time window was extended to 8 hours in an effort to further enhance enrolment. Participants or legally authorised representatives are informed about the trial and its anticipated risks orally and in written form using an approved informed consent form prior to inclusion. The findings of this study will be disseminated to the participants and to academic peers through scientific conferences and peer-reviewed journal publications.Trial registration numbersNCT02524379and 2014H0335.

scholarly journals Detection and Analysis of Perfusion Pressure through Measuring Oxygen Saturation and Requirement of Dural Incision Decompression after Laminectomy

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Jamal Alshorman ◽  
Yulong Wang ◽  
Guixiong Huang ◽  
Tracy Boakye Serebour ◽  
Xiaodong Guo
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Blood Flow ◽  
Oxygen Saturation ◽  
Spine Injury ◽  
Secondary Injury ◽  
Traumatic Spinal Cord Injury ◽  
Trauma Patients ◽  
Injury Site ◽  
Cord Injury

Background. Traumatic spinal cord injury (SCI) can continue and transform long after the time of initial injury. Preventing secondary injury after SCI is one of the most significant challenges, and early intervention to return the blood flow at the injury site can minimize the likelihood of secondary injury. Objective. The purpose of this study is to investigate whether laminectomy can achieve the spinal cord blood flow by measuring the spinal blood oxygen saturation intraoperatively without the presence of light. Methods. Between June and August 2021, eight patients were admitted after traumatic spinal cord injury for surgical treatment. We explored the effectiveness of laminectomy and whether the patients required further procedures or not. We used a brain oxygen saturation monitor at the spine injury site under dark conditions. Results. Eight cervical trauma patients, six males and two females, underwent laminectomy decompression. Three patients’ ASIA grade improved by one level, and one patient showed slight motor-sensory improvement. Oxygen saturation was in the normal range. Conclusion. Performing bony decompression can show good results. Therefore, finding an examination method to confirm the improvement of blood perfusion by measuring oxygen saturation at the injury site after laminectomy is essential to avoid other complications.

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