a-contusive-model-unilateral-cervical-spinal-cord-injury-using

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of ...

University of British Columbia 

A number of drugs commonly used for a variety of clinical indications have been found recently to have substantial neuroprotective properties, raising the potential for rapid translation into human clinical trials of spinal cord injury (SCI). In this study we compared the neuroprotective efficacy of erythropoietin and a derivative of it, darbepoetin, in an acute model of thoracic SCI. Sprague-Dawley rats were randomized to receive erythropoietin (5000 IU/kg), darbepoetin (10 mug/kg), or saline, as a single intravenous injection 1 h after a thoracic contusion SCI. The animals were evaluated for behavioral recovery over 6 weeks, which included BBB locomotor testing, horizontal ladder testing, video-analysis of gait, and hindlimb monofilament sensory testing. At 6 week post-injury, the spinal cords were evaluated histologically to measure white and grey matter sparing at and around the epicenter of injury. We found that neither erythropoietin nor darbepoetin led to improved behavioral recovery over saline controls, with no significant differences observed in BBB scores, BBB subscores, footfall errors on horizontal ladder testing, width of hindlimb base of support, or threshold for paw withdrawal on sensory testing. Furthermore, no differences were observed in grey or white matter sparing between the three experimental groups. Using doses of erythropoietin and darbepoetin that other investigators have reported to be beneficial in SCI and stroke models, we were unable to demonstrate a neuroprotective effect when administered 1 h after injury. Further preclinical investigation is necessary to refine the treatment strategy of using erythropoietin or darbepoetin in acute spinal cord injury.

Delayed treatment of spinal cord injury with erythropoietin or darbepoetin--a lack of neuroprotective efficacy in a contusion model of cord injury.

Spinal cord injury typically results in limited functional recovery. Here we investigated whether therapeutic dietary restriction, a multi-faceted, safe, and clinically-feasible treatment, can improve outcome from cervical spinal cord injury. The well-established notion that dietary restriction increases longevity has kindled interest in its potential benefits in injury and disease. When followed for several months prior to insult, prophylactic dietary restriction triggers multiple molecular responses and improves outcome in animal models of stroke and myocardial infarction. However, the efficacy of the clinically-relevant treatment of post-injury dietary restriction is unknown. Here we report that "every-other-day fasting" (EODF), a form of dietary restriction, implemented after rat cervical spinal cord injury was neuroprotective, promoted plasticity, and improved behavioral recovery. Without causing weight loss, EODF improved gait-pattern, forelimb function during ladder-crossing, and vertical exploration. In agreement, EODF preserved neuronal integrity, dramatically reduced lesion volume by >50%, and increased sprouting of corticospinal axons. As expected, blood beta-hydroxybutyrate levels, a ketone known to be neuroprotective, were increased by 2-3 fold on the fasting days. In addition, we found increased ratios of full-length to truncated trkB (receptor for brain-derived neurotrophic factor) in the spinal cord by 2-6 folds at both 5 days (lesion site) and 3 weeks after injury (caudal to lesion site) which may further enhance neuroprotection and plasticity. Because EODF is a safe, non-invasive, and low-cost treatment, it could be readily translated into the clinical setting of spinal cord injury and possibly other insults.

Dietary restriction started after spinal cord injury improves functional recovery.

Intravenously administered magnesium has been extensively investigated as a neuroprotective agent traumatic brain injuries and stroke. Numerous investigators have reported the neuroprotective benefits of magnesium in animal models of spinal cord injury (SCI) as well, but typically with doses that far exceed human tolerability. To develop magnesium into a clinically relevant therapy for SCI, further refinement and improvement of the magnesium formulation is necessary. In this series of experiments, we evaluated the neuroprotective efficacy of magnesium in a polyethylene glycol (PEG) formulation using an acute model of thoracic SCI. Following thoracic contusion (Infinite Horizon) rat SCI model, we independently confirmed the neuroprotective efficacy of the magnesium and PEG combination which had been previously reported in a thoracic clip compression model of SCI (Ditor et al., 2007). We established that the 254 micromol/kg dose of MgCl(2) was superior to 127 micromol/kg MgCl(2) with respect to tissue sparing and locomotor recovery. Additionally, the number of infusions (2, 4, or 6), time between infusions (6 vs 8 hours), and different magnesium salts (MgCl(2) vs MgSO(4)) were evaluated to determine an "optimal" treatment regimen. We observed that an "optimized" regimen of MgCl(2) within PEG conferred greater tissue neuroprotection and improved locomotor recovery compared to methylprednisolone. Further a 4 hour time window of histologic and behavioral efficacy was established. The goal of these experiments was to help guide the treatment parameters for a clinical trial of magnesium within a polyethylene glycol formulation in acute human spinal cord injury.

Magnesium chloride in a polyethylene glycol formulation as a neuroprotective therapy for acute spinal cord injury: preclinical refinement and optimization.

Although much progress has been made in the clinical care of patients with acute spinal cord injuries, there are no reliably effective treatments, which minimize secondary damage and improve neurologic outcome. The time and expense needed to establish de novo pharmacologic or biologic therapies for acute SCI has encouraged the development of neuroprotective treatments based on drugs that are already in clinical use and, therefore, have the advantage of a well-characterized safety and pharmacokinetic profile in humans. Statins are the most commonly prescribed class of lipid-lowering drugs, and recently, it has been recognized that statins also have powerful immunomodulatory and anti-inflammatory effects. This paper describes a series of experiments that were performed to evaluate the comparative neuroprotective effects of simvastatin and atorvastatin. We observed a promising signal of neurologic benefit with simvastatin in our first experiment, but in repeated attempts to replicate that effect in three subsequent experiments, we failed to reveal any behavioral or histologic improvements. We would conclude that simvastatin given orally or subcutaneously at doses previously reported by other investigators to be effective in different neurologic conditions does not confer a significant neurologic benefit in a thoracic contusion injury model (OSU Impactor) when administered with a 1-h delay in intervention. We contend that further preclinical investigation of atorvastatin and simvastatin is warranted before considering their translation into human SCI.

Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury.

Functional recovery after spinal cord injury (SCI) is limited, and the injury results in a dramatic reduction in long-term lifespan. Prophylactic dietary restriction (DR) robustly extends animal lifespan, and is beneficial in models of neuronal insult. In rats, we found that one form of DR, every-other-day-fasting (EODF), which started 1 month prior to a cervical SCI improved functional recovery, resulted in greater numbers of neurons surrounding the injury site, and a approximately 45% reduction in lesion size compared to the control group. In the light of the low-risk implementation of prophylactic EODF, the clinical translation as a treatment prior to elective subacute or chronic interventions is attractive. There are numerous secondary complications after human SCI, including a 13- to 25-year reduction in lifespan. DR consistently increases median and maximal lifespan in a large range of organisms, including non-human primates. Animal research suggests that EODF might reduce many of the secondary complications people with SCI suffer from. Dietary interventions may provide the possibility to improve the quality and span of life for individuals with SCI.

Prophylactic dietary restriction may promote functional recovery and increase lifespan after spinal cord injury.

Minocycline, a commonly prescribed tetracycline antibiotic, has shown promise as a potential therapeutic agent in animal models of numerous neurologic disorders such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Huntington's disease, stroke, and spinal cord injury (SCI). Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors prescribed to lower cholesterol. These drugs are also known to reduce inflammation and oxidative stress, improve endothelial function, and modulate the immune system in stroke, traumatic brain injury, and SCI. As both drugs have translational potential, we evaluated their neuroprotective properties here in a clinically relevant model of contusive cervical spinal cord injury. Sprague-Dawley rats underwent a unilateral cervical contusion SCI at C5 and were randomized to receive: 1. Minocycline 90 mg/kg x 3 days, 2. Simvastatin 20 mg/kg x 7 days, 3. Simvastatin 20 mg/kg x 7 days then 5mg/kg x 35 days, or 4. Saline (Control). Behavioral recovery was assessed over 6 weeks using the horizontal ladder test, cylinder rearing test, modified Montoya staircase test and grooming test. Forepaw sensitivity was also assessed using the electronic von Frey Aesthesiometer. The corticospinal and rubrospinal tracts were traced and the spinal cords were harvested 7 weeks after injury. The extent of gray matter and white matter sparing and corticospinal and rubrospinal tract sprouting were evaluated in cross sections of the spinal cord. In the end, neither minocycline nor simvastatin treatment was associated with improved performance on the behavioral tests, as compared to saline controls. Performance on the horizontal ladder test, cylinder rearing test, and von Frey sensory test were similar among all groups. Animals treated for 42 days with simvastatin scored significantly higher in the grooming score compared to other groups, but retrieved significantly fewer pellets on the modified Montoya staircase test than control and minocycline treated animals. Histologically, there were no significant differences in white and gray matter sparing and in the extent of corticospinal and rubrospinal sprouting between the four groups. In conclusion, both minocycline and simvastatin failed to improve functional and histological recovery in our model of contusive cervical spinal cord injury.

Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury.

Magnesium in a polyethylene glycol formulation provides neuroprotection after unilateral cervical spinal cord injury.

Spinal cord injury (SCI) often results in a loss of motor and sensory function. Currently there are no validated effective clinical treatments. Previously we found in rats that dietary restriction, in the form of every-other-day fasting (EODF), started prior to (pre-EODF), or after (post-EODF) an incomplete cervical SCI was neuroprotective, increased plasticity, and promoted motor recovery. Here we examined if EODF initiated prior to, or after, a T10 thoracic contusion injury would similarly lead to enhanced functional recovery compared to ad libitum feeding. Additionally, we tested if a group fed every day (pair-fed), but with the same degree of restriction as the EODF animals (∼25% calorie restricted), would also promote functional recovery, to examine if EODF's effect is due to overall calorie restriction, or is specific to alternating sequences of 24-h fasts and ad libitum eating periods. Behaviorally, both pre- and post-EODF groups exhibited better functional recovery in the regularity indexed BBB ambulatory assessment, along with several parameters of their walking pattern measured with the CatWalk device, compared to both the ad-libitium-fed group as well as the pair-fed group. Several histological parameters (intensity and symmetry of serotonin immunostaining caudal to the injury and gray matter sparing) correlated with functional outcome; however, no group differences were observed. Thus besides the beneficial effects of EODF after a partial cervical SCI, we now report that alternating periods of fasting (but not pair-fed) also promotes improved hindlimb locomotion after thoracic spinal cord contusion, demonstrating its robust effect in two different injury models.

Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury.

&#x810A;&#x9AD3;&#x635F;&#x4F24; (SCI) &#x7BA1;&#x7406;&#x9762;&#x4E34;&#x7684;&#x4E3B;&#x8981;&#x6311;&#x6218;&#x4E4B;&#x4E00;&#x662F;&#x635F;&#x4F24;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x7684;&#x8BC4;&#x4F30;&#x5F80;&#x5F80;&#x662F;&#x4E0D;&#x51C6;&#x786E;&#x7684;&#x3002;&#x53EF;&#x9760;&#x3001; &#x4E0D;&#x6613;&#x91CF;&#x5316;&#x7684;&#x751F;&#x7269;&#x6807;&#x5FD7;&#xFF0C;&#x5212;&#x5B9A;&#x6700;&#x521D;&#x7684;&#x635F;&#x4F24;&#x7684;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x548C;&#x9884;&#x540E;&#x529F;&#x80FD;&#x6062;&#x590D;&#x7684;&#x7A0B;&#x5EA6;&#x7684;&#x503C;&#x5C06;&#x5927;&#x5927;&#x6709;&#x52A9;&#x4E8E;&#x4E34;&#x5E8A;&#x533B;&#x5E08;&#x7684;&#x6F5C;&#x5728;&#x6CBB;&#x7597;&#x9009;&#x62E9;&#x5177;&#x6709;&#x7684;&#x6807;&#x8BC6;&#x3002;&#x82E5;&#x8981;&#x627E;&#x5230;&#x8FD9;&#x79CD;&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x6211;&#x4EEC;&#x6267;&#x884C;&#x5B9A;&#x91CF;&#x6DB2;&#x76F8;&#x8272;&#x8C31;-&#x8D28;&#x8C31; (LC-MS/MS) &#x8111;&#x810A;&#x6DB2; (CSF) &#x6216;&#x4E2D;&#x5EA6;&#x6216;&#x4E25;&#x91CD;&#x7684;&#x8D28;&#x63A7;&#x540E;&#x4ECE;&#x5927;&#x9F20; 24 h &#x6536;&#x96C6;&#x5206;&#x6790;&#x6211;&#x4EEC;&#x786E;&#x5B9A;&#x5C0F;&#x7EC4; 42 &#x5047;&#x5B9A;&#x5B58;&#x5728;&#x7684;&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x79D1;&#x6280;&#xFF0C;&#x5176;&#x4E2D; 10 &#x4EE3;&#x8868;&#x7684; SCI &#x4E25;&#x91CD;&#x6027;&#x7684;&#x6F5C;&#x5728;&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x3002;&#x4E09;&#x4E2A;&#x5019;&#x9009;&#x6807;&#x5FD7;&#x3001; Ywhaz&#x3001; Itih4&#x3001; &#x548C; Gpx3 &#x4E5F;&#x5370;&#x8BC1;&#x4E86;&#x4E2D;&#x897F;&#x635F;&#x4F24;&#x751F;&#x7269;&#x590D;&#x5236;&#x86CB;&#x767D;&#x514D;&#x75AB;&#x5370;&#x8FF9;&#x3002;&#x5728;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#x4E2D;&#x786E;&#x5B9A;&#x7684;&#x5047;&#x5B9A;&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x53EF;&#x80FD;&#x810A;&#x9AD3;&#x635F;&#x4F24;&#x7684;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x8BC4;&#x4F30;&#x7684;&#x5B9D;&#x8D35;&#x5DE5;&#x5177;&#x3002;

&#x751F;&#x7269;&#x6807;&#x5FD7;&#x7269;&#x5927;&#x9F20;&#x8111;&#x810A;&#x6DB2;&#x4E2D;&#x810A;&#x9AD3;&#x635F;&#x4F24;&#x7684;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x3002;

One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.

Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.

Un des d&eacute;fis majeurs dans la gestion de la moelle &eacute;pini&egrave;re (SCI) est que l&#39;&eacute;valuation de la gravit&eacute; de la blessure est souvent impr&eacute;cise. Identification de biomarqueurs fiables et facilement quantifiables qui d&eacute;limitent la gravit&eacute; de la blessure initiale et qui ont une valeur pronostique pour le degr&eacute; de r&eacute;cup&eacute;ration fonctionnelle faciliterait grandement le clinicien dans le choix des traitements potentiels. Pour trouver de tels biomarqueurs, nous avons effectu&eacute; des analyses quantitatives liquid chromatography-mass spectrometry (LC-MS/MS) du liquide c&eacute;phalo-rachidien (LCR) recueilli des rats 24h apr&egrave;s soit une SCI mod&eacute;r&eacute; ou s&eacute;v&egrave;re. Nous avons identifi&eacute; un groupe de 42 biomarqueurs putatifs de SCI, dont dix repr&eacute;sentent des biomarqueurs potentiels de s&eacute;v&eacute;rit&eacute; de la SCI. Trois des biomarqueurs candidats, Ywhaz, Itih4 et Gpx3 ont &eacute;t&eacute; &eacute;galement valid&eacute;es par Western blot dans une adaptation biologique de la blessure. Les biomarqueurs putatifs identifi&eacute;s dans cette &eacute;tude pourrait &ecirc;tre un outil pr&eacute;cieux dans l&#39;&eacute;valuation de l&#39;&eacute;tendue des l&eacute;sions de la moelle &eacute;pini&egrave;re.

Biomarqueurs de la gravit&eacute; des blessures de la moelle &eacute;pini&egrave;re dans le liquide c&eacute;phalorachidien des rats.

Eine der gr&ouml;&szlig;ten Herausforderungen im Management einer R&uuml;ckenmarksverletzung (SCI) ist, dass die Bewertung des Schweregrads der Verletzung oft ungenau. Identifizierung von Biomarkern f&uuml;r zuverl&auml;ssige, leicht quantifizierbare abzugrenzen, die den Schweregrad der urspr&uuml;nglichen Verletzung und die prognostische Wert f&uuml;r den Grad der funktionellen Erholung w&uuml;rde deutlich den Kliniker bei der Wahl der m&ouml;glichen Behandlungen helfen. Um solche Biomarker zu finden, f&uuml;hrten wir quantitative fl&uuml;ssige Chromatographie-Massenspektrometrie (LC-MS/MS) Analysen der Liquor cerebrospinalis (CSF) zusammengestellt von Ratten 24 h nach entweder ein mittlerer oder schwerer Sci. Wir ermittelt eine Jury aus 42 vermeintliche Biomarker von SCI, von die 10 potenzielle Biomarker SCI Schweregrad darstellen. Drei von den Kandidaten Biomarker, Ywhaz, Itih4 und Gpx3 wurden auch von westlichen validiert Fleck in einer biologischen Wiederholung der Verletzung. Die vermeintliche Biomarker identifiziert, die in dieser Studie k&ouml;nnen potenziell ein wertvolles Instrument bei der Beurteilung des Ausma&szlig;es der Sch&auml;den des R&uuml;ckenmarks sein.

Biomarker f&uuml;r die Schwere der Verletzung des R&uuml;ckenmarks in der Zerebrospinalfl&uuml;ssigkeit von Ratten.

Una delle sfide pi&ugrave; importanti nella gestione delle lesioni del midollo spinale (SCI) &egrave; che la valutazione della gravit&agrave; del pregiudizio &egrave; spesso imprecisa. Identificazione di biomarcatori affidabili, facilmente quantificabili che delineano la gravit&agrave; della lesione iniziale e che hanno un valore prognostico per il grado di recupero funzionale aiuterebbe notevolmente il clinico nella scelta dei trattamenti possibili. Per trovare tali biomarcatori abbiamo eseguito analisi quantitativa liquido cromatografia spettrometria di massa (LC-MS/MS) del liquido cerebrospinale (CSF) raccolti da ratti 24 h dopo sci o un moderato o grave. Abbiamo identificato un gruppo di 42 biomarcatori putativi di SCI, 10 dei quali rappresentano potenziali biomarcatori della severit&agrave; SCI. Anche tre dei biomarcatori candidato, Ywhaz, Itih4 e Gpx3 sono state convalidate da Western blot in una replica del pregiudizio biologica. I biomarcatori putativi identificati in questo studio possono essere potenzialmente uno strumento prezioso nella valutazione dell&#39;entit&agrave; dei danni del midollo spinale.

Biomarcatori per la gravit&agrave; delle lesioni del midollo spinale nel liquido cerebrospinale dei ratti.

&#x810A;&#x9AC4;&#x640D;&#x50B7; &#xFF08;SCI&#xFF09; &#x306E;&#x7BA1;&#x7406;&#x306B;&#x304A;&#x3051;&#x308B;&#x4E3B;&#x8981;&#x8AB2;&#x984C;&#x306E;&#x4E00;&#x3064;&#x306F;&#x50B7;&#x5BB3;&#x306E;&#x91CD;&#x75C7;&#x5EA6;&#x8A55;&#x4FA1;&#x306F;&#x3001;&#x3057;&#x3070;&#x3057;&#x3070;&#x6B63;&#x78BA;&#x3067;&#x306A;&#x3044;&#x3053;&#x3068;&#x3067;&#x3059;&#x3002;&#x521D;&#x671F;&#x306E;&#x640D;&#x50B7;&#x5EA6;&#x3092;&#x63CF;&#x304F;&#x3001;&#x6A5F;&#x80FD;&#x56DE;&#x5FA9;&#x306E;&#x7A0B;&#x5EA6;&#x306E;&#x4E88;&#x5F8C;&#x8A3A;&#x65AD;&#x5024;&#x3092;&#x6301;&#x3064;&#x4FE1;&#x983C;&#x6027;&#x306E;&#x9AD8;&#x3044;&#x3001;&#x5BB9;&#x6613;&#x306B;&#x5B9A;&#x91CF;&#x5316;&#x53EF;&#x80FD;&#x306A;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x306E;&#x540C;&#x5B9A;&#x306F;&#x5927;&#x5E45;&#x306B;&#x6F5C;&#x5728;&#x7684;&#x306A;&#x6CBB;&#x7642;&#x6CD5;&#x306E;&#x9078;&#x629E;&#x3067;&#x81E8;&#x5E8A;&#x533B;&#x3092;&#x52A9;&#x3051;&#x308B;&#x3060;&#x308D;&#x3046;.&#x8133;&#x810A;&#x9AC4;&#x6DB2; &#xFF08;CSF&#xFF09; &#x306F;&#x4E2D;&#x7B49;&#x5EA6;&#x307E;&#x305F;&#x306F;&#x91CD;&#x5EA6;&#x306E;&#x7406;&#x5F8C;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x304B;&#x3089; 24 h &#x306E;&#x53CE;&#x96C6;&#x306E;&#x5B9A;&#x91CF;&#x7684;&#x6DB2;&#x4F53;&#x30AF;&#x30ED;&#x30DE;&#x30C8;&#x30B0;&#x30E9;&#x30D5;&#x30A3;&#x30FC;&#x8CEA;&#x91CF;&#x5206;&#x6790;&#x6CD5; (LC-MS/MS) &#x89E3;&#x6790;&#x3092;&#x884C;&#x3063;&#x305F;&#x3053;&#x306E;&#x3088;&#x3046;&#x306A;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x3092;&#x691C;&#x7D22;&#x3059;&#x308B;&#x306B;&#x306F;&#x3001;&#x6211;&#x3005;&#x6211;&#x3005; &#x306F;&#x6F5C;&#x5728;&#x7684;&#x306A;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x306E; SCI &#x306E;&#x91CD;&#x5927;&#x5EA6;&#x304C; 10 &#x3092;&#x8868;&#x3059; 42 &#x63A8;&#x5B9A;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x306E; SCI&#x3001;&#x30D1;&#x30CD;&#x30EB;&#x8B58;&#x5225;&#x3002;3 &#x3064;&#x306E;&#x5019;&#x88DC;&#x8005;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x3001;Ywhaz&#x3001;Itih4&#x3001;&#x304A;&#x3088;&#x3073; Gpx3 &#x3082;&#x897F;&#x90E8;&#x306B;&#x3088;&#x3063;&#x3066;&#x691C;&#x8A3C;&#x3055;&#x308C;&#x305F;&#x3057;&#x307F;&#x50B7;&#x5BB3;&#x306E;&#x751F;&#x7269;&#x5B66;&#x7684;&#x8907;&#x88FD;&#x3067;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x8B58;&#x5225;&#x3055;&#x308C;&#x308B;&#x63A8;&#x5B9A;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x306F;&#x3001;&#x6F5C;&#x5728;&#x7684;&#x810A;&#x9AC4;&#x640D;&#x50B7;&#x306E;&#x7A0B;&#x5EA6;&#x306E;&#x8A55;&#x4FA1;&#x306B;&#x8CB4;&#x91CD;&#x306A;&#x30C4;&#x30FC;&#x30EB;&#x304B;&#x3082;&#x3057;&#x308C;&#x307E;&#x305B;&#x3093;&#x3002;

&#x91CD;&#x5927;&#x5EA6;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x8133;&#x810A;&#x9AC4;&#x6DB2;&#x4E2D;&#x306E;&#x810A;&#x9AC4;&#x306E;&#x50B7;&#x5BB3;&#x306E;&#x305F;&#x3081;&#x306E;&#x30D0;&#x30A4;&#x30AA; &#x30DE;&#x30FC;&#x30AB;&#x30FC;&#x3002;

&#xCC99;&#xC218; &#xC0C1;&#xD574; (SCI)&#xC758; &#xAD00;&#xB9AC;&#xC758; &#xC8FC;&#xC694; &#xACFC;&#xC81C; &#xC911; &#xD558;&#xB098;&#xAC00; &#xBD80;&#xC0C1; &#xC2EC;&#xAC01;&#xB3C4; &#xD3C9;&#xAC00; &#xC885;&#xC885; &#xC815;&#xD655;&#xD55C;&#xC785;&#xB2C8;&#xB2E4;. &#xC548;&#xC815;&#xC801;&#xC774; &#xACE0; &#xC27D;&#xAC8C; &#xC815;&#xB7C9; &#xBC14;&#xC774;&#xC624; &#xB9C8;&#xCEE4;&#xC758; &#xCD08;&#xAE30; &#xBD80;&#xC0C1;&#xC758; &#xC2EC;&#xAC01;&#xB3C4; &#xC724;&#xACFD;&#xC744; &#xADF8;&#xB9AC; &#xB2E4; &#xD558;&#xB294; &#xACE0; &#xAE30;&#xB2A5; &#xD68C;&#xBCF5;&#xC758; &#xC815;&#xB3C4; &#xB300; &#xD55C; &#xC804;&#xC870; &#xAC12; &#xC2DD;&#xBCC4; &#xD06C;&#xAC8C; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xCE58;&#xB8CC; &#xC120;&#xD0DD;&#xC5D0; &#xC784;&#xC0C1; &#xC9C0;&#xC6D0;. &#xC774;&#xB7EC;&#xD55C; &#xBC14;&#xC774;&#xC624; &#xB9C8;&#xCEE4;&#xC758; &#xBC1C;&#xACAC;&#xC744; &#xC6B0;&#xB9AC;&#xB294; &#xB1CC; &#xCC99;&#xCD94; &#xC561;&#xCCB4; (CSF) &#xC911;&#xAC04; &#xB610;&#xB294; &#xC2EC;&#xD55C; &#xACFC;&#xD559; &#xD6C4; &#xC950; 24h&#xC5D0;&#xC11C;&#xC5D0;&#xC11C; &#xC218;&#xC9D1; &#xB41C; &#xC591;&#xC801; &#xC561;&#xCCB4; &#xD06C;&#xB85C;&#xB9C8;&#xD1A0;&#xADF8;&#xB798;&#xD53C;-&#xC9C8;&#xB7C9; &#xBD84;&#xC11D; (LC-MS/MS) &#xBD84;&#xC11D;&#xC744; &#xC218;&#xD589; &#xC6B0;&#xB9AC;&#xB294; 10 &#xB300;&#xD45C; SCI &#xC2EC;&#xAC01;&#xB3C4;&#xC758; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xBC14;&#xC774;&#xC624; &#xB9C8;&#xCEE4;&#xC758; sci, 42 &#xC0C1; biomarkers&#xC758; &#xD328;&#xB110; &#xD655;&#xC778;. &#xD6C4;&#xBCF4; &#xC0DD;&#xCCB4;, Ywhaz, Itih4, &#xBC0F; gpx3&#xC758; &#xC138;&#xB3C4; &#xC11C;&#xC591;&#xC5D0;&#xC11C; &#xD655;&#xC778; &#xD588;&#xB2E4; &#xBD80;&#xC0C1; &#xC0DD;&#xBB3C; &#xBCF5;&#xC81C;&#xC5D0;&#xC11C; &#xB418; &#xB9AC;. &#xC774; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C; &#xD655;&#xC778; &#xB41C; &#xC0C1; biomarkers &#xCC99;&#xC218; &#xC190;&#xC0C1;&#xC758; &#xC815;&#xB3C4; &#xD3C9;&#xAC00; &#xD558;&#xB294; &#xC720;&#xC6A9;&#xD55C; &#xB3C4;&#xAD6C;&#xAC00; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC950;&#xC758; &#xCC99;&#xC218;&#xC5D0;&#xC11C; &#xCC99;&#xC218; &#xC190;&#xC0C1;&#xC758; &#xC2EC;&#xAC01;&#xB3C4; &#xB300; &#xD55C; &#xC0DD;&#xCCB4;.

Uno de los mayores desaf&iacute;os en la gesti&oacute;n de lesi&oacute;n de la m&eacute;dula espinal (SCI) es que la evaluaci&oacute;n de la gravedad de la lesi&oacute;n suele ser imprecisa. Identificaci&oacute;n de biomarcadores confiables, f&aacute;cilmente cuantificables que delinean la gravedad de la lesi&oacute;n inicial y que tienen valor pron&oacute;stico para el grado de recuperaci&oacute;n funcional ayudar&iacute;a significativamente al cl&iacute;nico en la elecci&oacute;n de tratamientos potenciales. Para encontrar estos biomarcadores se realizaron an&aacute;lisis de espectrometr&iacute;a de masa l&iacute;quida cuantitativa (LC-MS/MS) de l&iacute;quido cefalorraqu&iacute;deo (LCR) recogidos de ratas 24 h despu&eacute;s de ya sea una m&eacute;dula espinal moderada o severa. Identificamos un panel de 42 posibles biomarcadores de SCI, 10 de los cuales representan potenciales biomarcadores de la severidad de la SCI. Tres de los biomarcadores del candidato, Ywhaz, Itih4 y Gpx3 tambi&eacute;n fueron validados por Western blot en una repetici&oacute;n biol&oacute;gica de la lesi&oacute;n. Los supuesta biomarcadores identificados en este estudio pueden ser potencialmente una herramienta valiosa para la evaluaci&oacute;n de la magnitud del da&ntilde;o de la m&eacute;dula espinal.

Biomarcadores para la gravedad de la lesi&oacute;n de la m&eacute;dula espinal en el l&iacute;quido cerebroespinal de ratas.

Spinal cord injury (SCI) often results in considerable permanent neurological impairment, and unfortunately, the successful translation of effective treatments from laboratory models to human patients is lacking. This may be partially attributed to differences in anatomy, physiology, and scale between humans and rodent models. One potentially important difference between the rodent and human spinal cord is the presence of a significant CSF volume within the intrathecal space around the human cord. While the CSF may "cushion" the spinal cord, pressure waves within the CSF at the time of injury may contribute to the extent and severity of the primary injury. The objective of this study was to develop a model of contusion SCI in a miniature pig and establish the feasibility of measuring spinal CSF pressure during injury.

Article	Year
The Journal of neuroscience : the official journal of the Society for Neuroscience\| PubMed ID: 17522325	2007
Delayed treatment of spinal cord injury with erythropoietin or darbepoetin--a lack of neuroprotective efficacy in a contusion model of cord injury. Experimental neurology\| PubMed ID: 18313052	2008
Dietary restriction started after spinal cord injury improves functional recovery. Experimental neurology\| PubMed ID: 18585708	2008
Magnesium chloride in a polyethylene glycol formulation as a neuroprotective therapy for acute spinal cord injury: preclinical refinement and optimization. Journal of neurotrauma\| PubMed ID: 19317592	2009
Lack of robust neurologic benefits with simvastatin or atorvastatin treatment after acute thoracic spinal cord contusion injury. Experimental neurology\| PubMed ID: 19931252	2010
Prophylactic dietary restriction may promote functional recovery and increase lifespan after spinal cord injury. Annals of the New York Academy of Sciences\| PubMed ID: 20590533	2010
Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury. Experimental neurology\| PubMed ID: 20599974	2010
Magnesium in a polyethylene glycol formulation provides neuroprotection after unilateral cervical spinal cord injury. Spine\| PubMed ID: 20938394	2010
Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury. Journal of neurotrauma\| PubMed ID: 21219083	2011
Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats. PloS one\| PubMed ID: 21559420	2011
Development of a large-animal model to measure dynamic cerebrospinal fluid pressure during spinal cord injury: Laboratory investigation. Journal of neurosurgery. Spine\| PubMed ID: 22519927	2012

Jae H.T. Lee

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