Low-level laser therapy for spinal cord injury in rats: effects of polarization

Abstract. The effects of laser polarization on the efficacy of near-infrared low-level laser therapy for spinal cord injury (SCI) are presented. Rat spinal cords were injured with a weight-drop device, and the lesion sites were directly irradiated with a linearly polarized 808-nm diode laser positioned either perpendicular or parallel to the spine immediately after the injury and daily for five consecutive days. Functional recovery was assessed daily by an open-field test. Regardless of the polarization direction, functional scores of SCI rats that were treated with the 808-nm laser irradiation were significantly higher than those of SCI alone group (Group 1) from day 5 after injury. The locomotive function of SCI rats irradiated parallel to the spinal column (Group 3) was significantly improved from day 10 after injury, compared to SCI rats treated with the linear polarization perpendicular to the spinal column (Group 2). There were no significant differences in ATP contents in the injured tissue among the three groups. We speculate that the higher efficacy with parallel irradiation is attributable to the deeper light penetration into tissue with anisotropic scattering

Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study

<p>Abstract</p> <p>Background</p> <p>In acute stage of cerebral infarction, MRI indices (rDWI & rADC) deteriorate during the first 3-7 days after the ictus and then gradually normalize in approximately 10 days (pseudonormalization time), although the tissue is already infarcted. Since effective treatments improve these indices significantly and in less than the natural pseudonormalization time, a combined analysis of these changes provides an opportunity for objective evaluation on the effectiveness of various treatments for cerebral infarction. Hydroxyl radicals are highly destructive to the tissue and aggravate cerebral infarction. We treated brainstem infarction patients in acute stage with hydroxyl radical scavengers (Edaravone and hydrogen) by intravenous administration and evaluated the effects of the treatment by a serial observation and analysis of these MRI indices. The effects of the treatment were evaluated and compared in two groups, an Edaravone alone group and a combined group with Edaravone and hydrogen, in order to assess beneficial effects of addition of hydrogen.</p> <p>Methods</p> <p>The patients were divided in Edaravone only group (E group. 26 patients) and combined treatment group with Edaravone and hydrogen enriched saline (EH group. 8 patients). The extent of the initial hump of rDWI, the initial dip of rADC and pseudo-normalization time were determined in each patient serially and averages of these data were compared in these two groups and also with the natural course in the literatures.</p> <p>Results</p> <p>The initial hump of rDWI reached 2.0 in the E group which was better than 2.5 of the natural course but was not as good as 1.5 of the EH group. The initial dip of rADC was 0.6 in the E group which was close to the natural course but worse than 0.8 of the EH group. Pseudonormalization time of rDWI and rADC was 9 days only in EH group but longer in other groups. Addition of hydrogen caused no side effects.</p> <p>Conclusions</p> <p>Administration of hydroxyl radical scavengers in acute stage of brainstem infarction improved MRI indices against the natural course. The effects were more obvious and significant in the EH group. These findings may imply the need for more frequent daily administration of hydroxyl scavenger, or possible additional hydrogen effects on scavenger mechanisms.</p

Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage

BACKGROUND: Subarachnoid hemorrhage (SAH) often causes a prolongation of the corrected QT (QTc) interval during the acute phase. The aim of the present study was to examine independent risk factors for QTc prolongation in patients with SAH by means of multivariate analysis. METHOD: We studied 100 patients who were admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography (ECG) was performed immediately after admission. QT intervals were measured from the ECG and were corrected for heart rate using the Bazett formula. We measured serum levels of sodium, potassium, calcium, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose. RESULTS: The average QTc interval was 466 ± 46 ms. Patients were categorized into two groups based on the QTc interval, with a cutoff line of 470 ms. Univariate analyses showed significant relations between categories of QTc interval, and sex and serum concentrations of potassium, calcium, or glucose. Multivariate analyses showed that female sex and hypokalemia were independent risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was associated with a relative risk of 4.53 for severe QTc prolongation as compared with normokalemia, while the relative risk associated with female sex was 4.45 as compared with male sex. There was a significant inverse correlation between serum potassium levels and QTc intervals among female patients. CONCLUSION: These findings suggest that female sex and hypokalemia are independent risk factors for severe QTc prolongation in patients with SAH

Postoperative Spinal Epidural Hematoma: Risk Factor and Clinical Outcome

We report a series of epidural hematomas which cause neurologic deterioration after spinal surgery, and have taken risk factors and prognostic factors into consideration. We retrospectively reviewed the database of 3720 cases of spine operation in a single institute over 7 years (1998 April-2005 July). Nine patients who demonstrated neurologic deterioration after surgery and required surgical decompression were identified. Factors postulated to increase the postoperative epidural hematoma and to improve neurologic outcome were investigated. The incidence of postoperative epidural hematoma was 0.24%. Operation sites were cervical 3 cases, thoracic 2 cases, and lumbar 4 cases. Their original diagnoses were tumor 3 cases, cervical stenosis 2 cases, lumbar stenosis 3 cases and herniated lumbar disc 1case. The symptoms of epidural hematomas were neurologic deterioration and pain. After decompression, clinical outcome revealed complete recovery in 3 cases (33.3%), incomplete recovery in 5 cases (55.6%) and no change in 1 case (11.1%). Factors increasing the risk of postoperative epidural hematoma were coagulopathy from medical illness or anticoagulation therapy (4 cases, 44.4%) and highly vascularized tumor (3 cases, 33.3%). The time interval to evacuation of complete recovery group (29.3 hours) was shorter than incomplete recovery group (66.3 hours). Patients with coagulopathy and highly vascularized tumor were more vulnerable to spinal epidural hematoma. The postoperative outcome was related to the preoperative neurological deficit and the time interval to the decompression

The cytokine tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 have a neuroprotective effect in the central nervous system

<p>Abstract</p> <p>Background</p> <p>Cerebral cortical neurons have a high vulnerability to the harmful effects of hypoxia. However, the brain has the ability to detect and accommodate to hypoxic conditions. This phenomenon, known as preconditioning, is a natural adaptive process highly preserved among species whereby exposure to sub-lethal hypoxia promotes the acquisition of tolerance to a subsequent lethal hypoxic injury. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) are found in neurons and their expression is induced by exposure to sub-lethal hypoxia. Accordingly, in this work we tested the hypothesis that the interaction between TWEAK and Fn14 induces tolerance to lethal hypoxic and ischemic conditions.</p> <p>Methods</p> <p>Here we used <it>in vitro </it>and <it>in vivo </it>models of hypoxic and ischemic preconditioning, an animal model of transient middle cerebral artery occlusion and mice and neurons genetically deficient in TWEAK, Fn14, or tumor necrosis factor alpha (TNF-α) to investigate whether treatment with recombinant TWEAK or an increase in the expression of endogenous TWEAK renders neurons tolerant to lethal hypoxia. We used enzyme-linked immunosorbent assay to study the effect of TWEAK on the expression of neuronal TNF-α, Western blot analysis to investigate whether the effect of TWEAK was mediated by activation of mitogen-activated protein kinases and immunohistochemical techniques and quantitative real-time polymerase chain reaction analysis to study the effect of TWEAK on apoptotic cell death.</p> <p>Results</p> <p>We found that either treatment with recombinant TWEAK or an increase in the expression of TWEAK and Fn14 induce hypoxic and ischemic tolerance <it>in vivo </it>and <it>in vitro</it>. This protective effect is mediated by neuronal TNF-α and activation of the extracellular signal-regulated kinases 1 and 2 pathway via phosphorylation and inactivation of the B-cell lymphoma 2-associated death promoter protein.</p> <p>Conclusions</p> <p>Our work indicate that the interaction between TWEAK and Fn14 triggers the activation of a cell signaling pathway that results in the induction of tolerance to lethal hypoxia and ischemia. These data indicate that TWEAK may be a potential therapeutic strategy to protect the brain from the devastating effects of an ischemic injury.</p

Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats

<p>Abstract</p> <p>Background</p> <p>Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an <it>in vivo </it>rat model of acute ischemic stroke.</p> <p>Methods</p> <p>Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1β, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra.</p> <p>Results</p> <p>24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p = 0.001), cortical (p = 0.002), and basal ganglia (p = 0.036) infarct volumes. Hippocampal infarct volumes (p = 0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1β (79%; p < 0.001), TNF-α (59%; p = 0.001), IL-6 (47%; p = 0.04), and CD11B (49%; p = 0.001) in the infarcted cortex compared to controls.</p> <p>Conclusions</p> <p>Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.</p