OBJECTIVES: Spinal cord ischemia-reperfusion injury (SCIRI) remains a major challenge in the field of organ protection due to the lack of effective prevention and therapeutic strategies. Hyperglycemia, a common perioperative condition, contributes to neurological injury via multiple mechanisms. However, its role and underlying mechanism in SCIRI are still unclear. This study aims to investigate the involvement of the precursor of brain-derived neurotrophic factor (proBDNF) in hyperglycemia-induced SCIRI in mice. METHODS: Eight-week-old male C57BL/6 mice were randomly assigned to a control group (Vehicle) or a diabetes mellitus (DM) group. The DM group was established using intraperitoneal injection of streptozotocin (STZ) combined with 10% sucrose water. The Vehicle group received an equal volume of 50 mmol/L sodium citrate buffer (pH 4.5). Fasting blood-glucose levels ≥11.1 mmol/L were considered successful DM modeling. Both Vehicle and DM groups underwent SCIRI modeling via descending aortic clamping, while the Sham group underwent a sham procedure without aortic occlusion. Lower limb motor function was assessed using the Basso Mouse Scale (BMS) and its subscale (sub-BMS). Locomotor activity was evaluated using an open field test. Immunohistochemistry was performed to detect changes in neuronal nuclear protein (NeuN) and proBDNF expression in spinal cord tissues. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure mRNA expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). To explore the effect of proBDNF inhibition, diabetic mice were divided into groups: A DM+SCIRI+monoclonal anti-proBDNF antibody (McAb-proB) group received an intraperitoneal injection of 100 μg of McAb-proB 30 minutes before SCIRI modeling, and a DM+SCIRI+Vehicle group received an equal amount of isotype immunoglobulin G. BMS and sub-BMS scores were recorded, and the gene expression of inflammatory cytokines mentioned above were evaluated. RESULTS: Compared with the Vehicle+SCIRI group, the DM+SCIRI group showed significantly reduced BMS and sub-BMS scores, decreased NeuN expression, shorter total movement distance, slower locomotion, increased proBDNF expression, and elevated IL-1β, IL-6, and TNF-α mRNA levels (all P<0.05 or P<0.01). Compared with the DM+SCIRI+Vehicle group, the DM+SCIRI+McAb-proB group exhibited significantly improved BMS and sub-BMS scores and decreased mRNA expression of IL-1β, IL-6, and TNF-α (all P<0.05 or P<0.01). CONCLUSIONS Hyperglycemia exacerbates neural injury and inflammatory response in SCIRI through upregulation of proBDNF expression, delaying motor functional recovery. Antagonizing proBDNF expression can alleviate neurological damage and promote functional recovery in diabetic mice after SCIRI.
Animals ; Male ; Hyperglycemia/metabolism* ; Brain-Derived Neurotrophic Factor/genetics* ; Mice, Inbred C57BL ; Reperfusion Injury/metabolism* ; Mice ; Diabetes Mellitus, Experimental/metabolism* ; Inflammation/metabolism* ; Disease Models, Animal ; Spinal Cord/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Protein Precursors/genetics* ; Spinal Cord Ischemia/metabolism* ; Interleukin-6/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE: The purpose of this study was to determine whether xenon post-conditioning affects mTOR signaling as well as endoplasmic reticulum stress (ERS)-apoptosis pathway in rats with spinal cord ischemia/reperfusion injury. METHODS: Fifty male rats were randomized equally into sham-operated group (Sham group), I/R model group (I/R group), I/R model+ xenon post-conditioning group (Xe group), I/R model+rapamycin (a mTOR signaling pathway inhibitor) treatment group (I/R+ Rapa group), and I/R model + xenon post- conditioning with rapamycin treatment group (Xe + Rapa group).. In the latter 4 groups, SCIRI was induced by clamping the abdominal aorta for 85 min followed by reperfusion for 4 h. Rapamycin (or vehicle) was administered by daily intraperitoneal injection (4 mg/kg) for 3 days before SCIRI, and xenon post-conditioning by inhalation of 1∶1 mixture of xenon and oxygen for 1 h at 1 h after initiation of reperfusion; the rats without xenon post-conditioning were given inhalation of nitrogen and oxygen (1∶ 1). After the reperfusion, motor function and histopathologic changes in the rats were examined. Western blotting and real-time PCR were used to detect the protein and mRNA expressions of GRP78, ATF6, IRE1α, PERK, mTOR, p-mTOR, Bax, Bcl-2 and caspase-3 in the spinal cord. RESULTS: The rats showed significantly lowered hind limb motor function following SCIRI (P < 0.01) with a decreased count of normal neurons, increased mRNA and protein expressions of GRP78, ATF6, IRE1α, PERK, and caspase-3, and elevated p-mTOR/mTOR ratio and Bax/Bcl-2 ratio (P < 0.01). Xenon post-conditioning significantly decreased the mRNA and protein levels of GRP78, ATF6, IRE1α, PERK and caspase-3 (P < 0.05 or 0.01) and reduced p-mTOR/mTOR and Bax/Bcl-2 ratios (P < 0.01) in rats with SCIRI; the mRNA contents and protein levels of GRP78 and ATF6 were significantly decreased in I/R+Rapa group (P < 0.01). Compared with those in Xe group, the rats in I/R+Rapa group and Xe+Rapa had significantly lowered BBB and Tarlov scores of the hind legs (P < 0.01), and caspase-3 protein level and Bax/Bcl-2 ratio were significantly lowered in Xe+Rapa group (P < 0.05 or 0.01). CONCLUSION By inhibiting ERS and neuronal apoptosis, xenon post- conditioning may have protective effects against SCIRI in rats. The mTOR signaling pathway is partially involved in this process.
Animals ; Apoptosis ; Caspase 3/metabolism* ; Endoplasmic Reticulum Stress ; Endoribonucleases/pharmacology* ; Injections, Intraperitoneal ; Male ; Neurons/pathology* ; Nitrogen/metabolism* ; Oxygen/metabolism* ; Protein Serine-Threonine Kinases ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Sirolimus/pharmacology* ; Spinal Cord Ischemia/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Xenon/therapeutic use* ; bcl-2-Associated X Protein/metabolism*

STUDY DESIGN: Retrospective database analysis. PURPOSE: To identify risk factors that predict mortality following acute spine fractures in geriatric patients of Singapore. OVERVIEW OF LITERATURE: Acute geriatric spinal fractures contribute significantly to local healthcare costs and hospital admissions. However, geriatric mortality following acute spine fractures is scarcely assessed in the Asian population. METHODS: Electronic records of 3,010 patients who presented to our hospital’s emergency department and who were subsequently admitted during 2004–2015 with alleged history of traumatic spine fractures were retrospectively reviewed, and 613 patients (mean age, 85.7±4.5 years; range, 80–101 years; men, 108; women, 505) were shortlisted. Mortality rates were reviewed up to 1 year after admission and multivariate analyses were performed to identify independent risk factors correlating with mortality. RESULTS: Women were more susceptible to spine fractures (82.4%), with falls (77.8%) being the most common mechanism of injury. Mortality rates were 6.0%, 8.2%, and 10.4% at 3, 6, and 12 months, respectively. The most common causes of death at all 3 time points were pneumonia and ischemic heart disease. Based on the multivariate analysis at 1-year follow-up, elderly women had a lower mortality rate compared to men (p<0.001); mortality rates increased by 6.3% (p=0.024) for every 1-year increase in the patient’s age; and patients with an American Spinal Injury Association (ASIA) score of A–C had a much higher mortality rate compared to those with an ASIA score of D–E (p<0.001). CONCLUSIONS: An older age at presentation, male sex, and an ASIA score of A–C were identified as independent factors predicting increased mortality among geriatric patients who sustained acute spine fractures. The study findings highlight at-risk groups for acute spine fractures, thereby providing an opportunity to develop strategies to increase the life expectancy of these patients.
Accidental Falls ; Aged ; Asia ; Asian Continental Ancestry Group ; Cause of Death ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Health Care Costs ; Humans ; Life Expectancy ; Male ; Mortality ; Multivariate Analysis ; Myocardial Ischemia ; Pneumonia ; Retrospective Studies ; Risk Factors ; Singapore ; Spinal Cord Injuries ; Spinal Fractures ; Spinal Injuries ; Spine

We describe a case of vertebral artery dissection (VAD) presenting with acute infarctions in cervical spinal cord and cerebellum in a 78-year-old man. Diffusion-weighted magnetic resonance (MR) imaging of the brain demonstrated diffusion-restricted lesions in the right cerebellum and sagittal T2-weighted MR imaging of spinal cord showed a hyperintense lesion of the cervical spinal cord at C2-C4 level. Right VAD was identified by transfemoral cerebral angiography and computed tomography angiography which showed segmental occlusion in the right vertebral artery.
Aged ; Angiography ; Brain ; Cerebellum ; Cerebral Angiography ; Cervical Cord ; Humans ; Infarction ; Magnetic Resonance Imaging ; Spinal Cord ; Spinal Cord Ischemia ; Vertebral Artery Dissection ; Vertebral Artery

No abstract available.
Anterior Spinal Artery Syndrome ; Hemiplegia ; Infarction ; Paresis ; Spinal Cord

Peripheral arterial disease is one part of systematic atherosclerosis, becoming a heavy burden of human health. Patients in end stage of peripheral arterial disease manifest critical limb ischemia with severe rest pain and refractory ulcer. Surgical revascularization is the optimal option for patients with critical limb ischemia to avoid major amputation and improve quality of life. However, some of them contraindicate surgical revascularizations owing to coexisting morbidities. Spinal cord stimulation is reported to be effective and minimally invasive in pain relief and limb salvage for patients with limb ischemia. Here, we reported one case with chronic critical limb ischemia and gangrene of foot who underwent spinal cord stimulation, which was, as we knew, the first case in China. He was diagnosed with Burger disease and accompanied with history of stroke, chronic obstructive pulmonary disease and Castleman's disease. It showed totally occlusive lesions of external iliac and femoropopliteal artery and no outflows below the knee in the computed tomography angiography. Given the complexity of lesions and weakness of the patient, spinal cord stimulation was indicated for control of rest pain and limb salvage. As specified, we implanted the temporary neurostimulator as the first step. After 2 weeks from temporary neurostimulator implantation, the patient achieved significant relief in intensity of pain, and acquired 20% improvement of transcutaneous oxygen pressure. The satisfactory results indicated probable effectiveness of spinal cord stimulation, thus we performed the permanent neurostimulator implantation 1 month later. During 2 months of follow-up, the patients stabilized at Fountain III with pain relief with one kind of nonsteroidal anti-inflammatory drug. In our case, we confirmed the significant validity of spinal cord stimulation for pain control and consequent improvement of quality of life in non-reconstructable chronic critical limb ischemia. Furthermore, we reviewed that a number of published studies suggested that spinal cord stimulation be a reasonable option for patients with critical rest pain, especially who contraindicated surgical revascularization. The application of spinal cord stimulation in pain relief for non-reconstructable chronic critical limb ischemia was approved by related guidelines released by European Society of Cardiology and Trans-Atlantic Inter-Society Consensus. Further investigations are required for assessing the long-term outcome in limb salvage.
China ; Humans ; Ischemia ; Leg ; Limb Salvage ; Male ; Quality of Life ; Spinal Cord ; Spinal Cord Stimulation ; Treatment Outcome

Fatal arrhythmias, heart failure, and sudden cardiac death after myocardial ischemia/infarction are serious threats to human health. In recent years, studies have shown that spinal cord stimulation (SCS) can balance autonomic activity, inhibit myocardial structural remodeling, improve blood flow to ischemic myocardium, effectively reduce the incidence of arrhythmia, heart failure and sudden cardiac death after myocardial ischemia/infarction, but its specific mechanism has not yet been fully elucidated. The effect of SCS on cardiac function may be achieved by inhibiting neural remodeling, or by ameliorating structural remodeling and electrical remodeling. This article reviews the progress on the role and mechanism of SCS in myocardial ischemia/infarction.
Coronary Artery Disease ; Heart Failure ; Humans ; Myocardial Infarction ; therapy ; Myocardial Ischemia ; Myocardium ; Spinal Cord Stimulation

We present a patient with metastatic colon carcinoma who developed paraplegia following a neurolytic splanchnic block. A 41-year old man with metastatic adenocarcinoma of the colon received a splanchnic neurolytic block using alcohol because of severe abdominal pain. Bilateral motor weakness and a sensorial deficit in both legs developed after the procedure. Diffusion magnetic resonance imaging revealed spinal cord ischemia between T8 and L1. The motor and sensorial deficits were almost completely resolved at the end of the third month. We think that anterior spinal artery syndrome due to reversible spasms of the lumbar radicular arteries using alcohol have resulted in transient paraplegia. The retrograde spread of alcohol to neural structures may have also contributed.
Abdominal Pain ; Adenocarcinoma ; Anterior Spinal Artery Syndrome ; Arteries ; Colon ; Diffusion Magnetic Resonance Imaging ; Humans ; Leg ; Paraplegia ; Spasm ; Spinal Cord Ischemia

A 77-year-old female with a history of osteoarthritis visited our clinic complaining of lower back pain, paresthesia in both legs, and voiding difficulty. Her pain and temperature sensations were diminished below the L1 dermatome, and proprioception was decreased in both feet. The findings of a routine laboratory workup, echocardiogram, and cerebrospinal fluid studies were normal. Spine magnetic resonance imaging revealed high T2-weighted signal intensities and diffusion restriction in the posterior conus medullaris. The patient was diagnosed and treated for posterior spinal artery infarction.
Aged ; Arteries ; Cerebrospinal Fluid ; Conus Snail ; Diffusion ; Female ; Foot ; Humans ; Infarction ; Leg ; Low Back Pain ; Magnetic Resonance Imaging ; Osteoarthritis ; Paresthesia ; Proprioception ; Sensation ; Spinal Cord Compression ; Spinal Cord Ischemia ; Spinal Cord Vascular Diseases ; Spinal Cord ; Spine

STUDY DESIGN: A case report. OBJECTIVES: To report a rare cause of non-traumatic spinal cord injury (SCI) during surfing SUMMARY OF LITERATURE REVIEW: Surfer's myelopathy is a non-traumatic SCI associated with the hyperextension posture during paddling in surfing. Although the definite pathomechanism has not been identified, cord ischemia followed by arterial infarction may be related to this injury. MATERIALS AND METHODS: A young healthy male patient presented with a SCI that occurred during his first time surfing. Magnetic resonance imaging revealed a T2-hyperintense lesion in the spinal cord from D10 to the conus medullaris. RESULTS: The patient completely recovered without any neurologic deficits after steroid therapy and other forms of supportive management. CONCLUSIONS: Since surfing is becoming more common in Korea, awareness of surfer's myelopathy is important for early diagnosis and proper management.
Early Diagnosis ; Humans ; Infarction ; Ischemia ; Korea ; Magnetic Resonance Imaging ; Male ; Neurologic Manifestations ; Posture ; Spinal Cord ; Spinal Cord Diseases* ; Spinal Cord Injuries ; Spinal Cord Ischemia