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 

When stimulated strongly, a hair cell's mechanically sensitive hair bundle may consume ATP too rapidly for replenishment by diffusion. To provide a broad view of the bundle's protein complement, including those proteins participating in energy metabolism, we used shotgun mass spectrometry methods to identify proteins of purified chicken vestibular bundles. In addition to cytoskeletal proteins, proteins involved in Ca(2+) regulation, and stress-response proteins, many of the most abundant bundle proteins that were identified by mass spectrometry were involved in ATP synthesis. After beta-actin, the cytosolic brain isoform of creatine kinase was the next most abundant bundle protein; at approximately 0.5 mM, creatine kinase is capable of maintaining high ATP levels despite 1 mM/s ATP consumption by the plasma-membrane Ca(2+)-ATPase. Consistent with this critical role in hair bundle function, the creatine kinase circuit is essential for high-sensitivity hearing as demonstrated by hearing loss in creatine kinase knockout mice.

Hair bundles are specialized for ATP delivery via creatine kinase.

&#x673A;&#x68B0;&#x523A;&#x6FC0;&#x5F3A;&#x70C8;&#xFF0C;&#x6BDB;&#x7EC6;&#x80DE;&#x65F6;&#x654F;&#x611F;&#x5934;&#x53D1;&#x675F;&#x53EF;&#x80FD;&#x6D88;&#x8017; ATP &#x592A;&#x8FC5;&#x901F;&#x8865;&#x7ED9;&#x7684;&#x6269;&#x6563;&#x3002;&#x4E3A;&#x63D0;&#x4F9B;&#x7684;&#x6346;&#x7ED1;&#x86CB;&#x767D;&#x8D28;&#x7684;&#x8865;&#x5145;&#xFF0C;&#x5305;&#x62EC;&#x53C2;&#x4E0E;&#x80FD;&#x91CF;&#x4EE3;&#x8C22;&#xFF0C;&#x8FD9;&#x4E9B;&#x86CB;&#x767D;&#x8D28;&#x5E7F;&#x6CDB;&#x8BA4;&#x4E3A;&#x6211;&#x4EEC;&#x4F7F;&#x7528;&#x730E;&#x67AA;&#x8D28;&#x8C31;&#x65B9;&#x6CD5;&#x6765;&#x8BC6;&#x522B;&#x86CB;&#x767D;&#x7684;&#x7EAF;&#x5316;&#x7684;&#x9E21;&#x524D;&#x5EAD;&#x675F;&#x3002;&#x7EC6;&#x80DE;&#x9AA8;&#x67B6;&#x86CB;&#x767D;&#xFF0C;&#x53C2;&#x4E0E;&#x7ECF;&#x8C03;&#x8282;&#x86CB;&#x767D;&#x53CA;&#x5E94;&#x6FC0;&#x53CD;&#x5E94;&#x86CB;&#x767D;&#xFF0C;&#x9664;&#x4E86;&#x8BB8;&#x591A;&#x7684;&#x6700;&#x4E30;&#x5BCC;&#x7684;&#x6346;&#x7ED1;&#x86CB;&#x767D;&#x8D28;&#x8D28;&#x8C31;&#x6CD5;&#x88AB;&#x8BA4;&#x5B9A;&#x53C2;&#x4E0E;&#x4E86; ATP &#x5408;&#x6210;&#x3002;&#x540E; &beta;-&#x808C;&#x52A8;&#x86CB;&#x767D;&#xFF0C;&#x80DE;&#x6D46;&#x8111;&#x5F02;&#x6784;&#x4F53;&#x7684;&#x808C;&#x9178;&#x6FC0;&#x9176;&#x662F;&#x4E0B;&#x4E00;&#x6B65;&#x6700;&#x4E30;&#x5BCC;&#x7684;&#x6346;&#x7ED1;&#x86CB;&#x767D;&#x8D28; &#xFF1B;&#x5728;&#x5927;&#x7EA6; 0.5 m m&#xFF0C;&#x808C;&#x9178;&#x6FC0;&#x9176;&#x662F;&#x80FD;&#x591F;&#x7EF4;&#x6301;&#x9AD8; ATP &#x6C34;&#x5E73;&#x5C3D;&#x7BA1;&#x7B49;&#x79BB;&#x5B50;&#x819C; Ca(2+)-ATPase 1 m m s ATP &#x6D88;&#x8017;&#x3002;&#x7B26;&#x5408;&#x8FD9;&#x5934;&#x53D1;&#x675F;&#x51FD;&#x6570;&#x4E2D;&#x7684;&#x5173;&#x952E;&#x4F5C;&#x7528;&#xFF0C;&#x808C;&#x9178;&#x6FC0;&#x9176;&#x7535;&#x8DEF;&#x662F;&#x9AD8;&#x7075;&#x654F;&#x5EA6;&#x7684;&#x8046;&#x8BAF;&#x4E2D;&#x808C;&#x9178;&#x6FC0;&#x9176;&#x57FA;&#x56E0;&#x6572;&#x9664;&#x5C0F;&#x9F20;&#x7684;&#x542C;&#x529B;&#x635F;&#x5931;&#x6240;&#x793A;&#x7684;&#x5FC5;&#x8981;&#x6761;&#x4EF6;&#x3002;

&#x808C;&#x9178;&#x6FC0;&#x9176;&#x901A;&#x8FC7; ATP &#x63D0;&#x4F9B;&#x4E13;&#x4E1A;&#x7684;&#x6BDB;&#x4E1B;&#x3002;

Quand ils sont stimul&eacute;s fortement, une cellule cheveux m&eacute;caniquement bundle cheveux sensibles peut-&ecirc;tre consommer ATP trop rapidement pour le r&eacute;approvisionnement par diffusion. Afin de fournir une vue d&#39;ensemble du compl&eacute;ment de prot&eacute;ine de l&#39;ensemble, y compris les prot&eacute;ines participant au m&eacute;tabolisme &eacute;nerg&eacute;tique, nous avons utilis&eacute; m&eacute;thodes de spectrom&eacute;trie de masse de fusil de chasse afin d&#39;identifier les prot&eacute;ines des faisceaux vestibulaire poulet purifi&eacute;e. En plus des prot&eacute;ines du cytosquelette, prot&eacute;ines impliqu&eacute;es dans le r&egrave;glement de Ca(2+) et les prot&eacute;ines de la r&eacute;ponse au stress, beaucoup de prot&eacute;ines les plus abondantes du bundle qui ont &eacute;t&eacute; identifi&eacute;s par spectrom&eacute;trie de masse &eacute;taient impliqu&eacute;s dans la synth&egrave;se d&#39;ATP. Apr&egrave;s la beta-actine, l&#39;isoforme cytosolique de cerveau de la cr&eacute;atine kinase est la prochaine prot&eacute;ine la plus abondante bundle ; &agrave; environ 0,5 mM, la cr&eacute;atine kinase est capable de maintenir des niveaux &eacute;lev&eacute;s d&#39;ATP malgr&eacute; une consommation de 1 mM/s ATP par le Ca(2+)-ATPase de la membrane plasmique. Conform&eacute;ment &agrave; ce r&ocirc;le critique en fonction de faisceau de cheveux, le circuit de la cr&eacute;atine kinase est essentiel pour haute sensibilit&eacute; audience comme en t&eacute;moigne la surdit&eacute; chez les souris knock-out cr&eacute;atine kinase.

Faisceaux de cheveux est sp&eacute;cialis&eacute;s pour la livraison de ATP via la cr&eacute;atine kinase.

Wenn stark, eine Haarzelle mechanisch stimuliert kann empfindliche Haare B&uuml;ndel ATP zu schnell f&uuml;r Nachschub durch Diffusion verbrauchen. Um einen umfassenden &Uuml;berblick &uuml;ber das Bundle-Protein-Erg&auml;nzung, einschlie&szlig;lich diese Proteine, die Teilnahme am Energiestoffwechsel, verwendete wir Schrotflinte Massenspektrometrie Methoden um Proteine von gereinigtem Huhn vestibul&auml;ren b&uuml;ndeln zu identifizieren. Neben Zytoskelett-Proteine, Proteine Ca(2+) Regulierung beteiligt und Reaktion auf Stress Proteine, wurden viele der am h&auml;ufigsten vorkommenden B&uuml;ndel-Proteine, die durch Massenspektrometrie identifiziert wurden in der ATP-Synthese beteiligt. Die Zytosolische Gehirn-Isoform der Kreatin-Kinase als Beta-Actin wurde das n&auml;chste h&auml;ufigste B&uuml;ndel-Protein; bei ca. 0,5 mM ist Kreatin-Kinase ATP-hohe trotz 1 mM/s ATP-Verbrauch durch die Plasmamembran Ca(2+)-ATPase aufrechterhalten. In &Uuml;bereinstimmung mit dieser kritischen Rolle in Haar-B&uuml;ndel-Funktion, unbedingt die Kreatin-Kinase-Schaltung hochempfindlichen h&ouml;ren wie H&ouml;rverlust Kreatin-Kinase-Knockout-M&auml;usen demonstriert.

Haar-B&uuml;ndel sind f&uuml;r ATP-Bereitstellung &uuml;ber Kreatin-Kinase spezialisiert.

Quando stimolato fortemente, di una cella di capelli meccanicamente bundle capelli sensibili possa consumare ATP troppo rapidamente per rifornimento di diffusione. Per fornire una visione ampia del complemento di proteina del pacchetto, tra cui quelle proteine che partecipano nel metabolismo energetico, abbiamo utilizzato metodi di spettrometria di massa del fucile per identificare le proteine dei fasci vestibolari pollo purificato. Oltre a proteine del citoscheletro, proteine coinvolte nella regolazione di Ca(2+) e le proteine di risposta allo stress, molte delle proteine pi&ugrave; abbondanti bundle che sono state identificate tramite spettrometria totale sono stati coinvolti nella sintesi dell&#39;ATP. Dopo beta-actina, l&#39;isoforma citosolica cervello della creatinchinasi era pi&ugrave; abbondante proteina bundle successiva; a circa 0,5 mM, creatina chinasi &egrave; in grado di mantenere alti livelli di ATP nonostante il consumo di 1 mM/s ATP dalla Ca(2+)-atpasi di membrana del plasma. Coerenti con questo ruolo critico in funzione del fascio di capelli, il circuito creatina chinasi &egrave; essenziale per sentire come dimostrato dalla perdita dell&#39;udito nei topi knockout creatina chinasi ad alta sensibilit&agrave;.

Pacchi dei capelli sono specializzati per la consegna di ATP via creatina chinasi.

&#x654F;&#x611F;&#x306A;&#x9AEA;&#x30D0;&#x30F3;&#x30C9;&#x30EB; ATP &#x304C;&#x5F37;&#x304F;&#x3001;&#x6709;&#x6BDB;&#x7D30;&#x80DE;&#x306E;&#x6A5F;&#x68B0;&#x7684;&#x523A;&#x6FC0;&#x306B;&#x3088;&#x308B;&#x62E1;&#x6563;&#x3067;&#x306F;&#x3042;&#x307E;&#x308A;&#x306B;&#x3082;&#x6025;&#x901F;&#x306B;&#x88DC;&#x5145;&#x304C;&#x6D88;&#x8CBB;&#x53EF;&#x80FD;&#x6027;&#x304C;&#x3042;&#x308A;&#x307E;&#x3059;&#x3002;&#x30A8;&#x30CD;&#x30EB;&#x30AE;&#x30FC;&#x4EE3;&#x8B1D;&#x306B;&#x53C2;&#x52A0;&#x3057;&#x3066;&#x3044;&#x308B;&#x305D;&#x308C;&#x3089;&#x306E;&#x86CB;&#x767D;&#x8CEA;&#x3092;&#x542B;&#x3080;&#x30D0;&#x30F3;&#x30C9;&#x30EB;&#x306E;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;&#x88DC;&#x6570;&#x306E;&#x5E83;&#x3044;&#x8996;&#x91CE;&#x3092;&#x63D0;&#x4F9B;&#x3059;&#x308B;&#x306B;&#x306F;&#x3001;&#x79C1;&#x305F;&#x3061;&#x7CBE;&#x88FD;&#x30CB;&#x30EF;&#x30C8;&#x30EA;&#x524D;&#x5EAD;&#x795E;&#x7D4C;&#x675F;&#x306E;&#x86CB;&#x767D;&#x8CEA;&#x3092;&#x8B58;&#x5225;&#x3059;&#x308B;&#x306E;&#x306B;&#x6563;&#x5F3E;&#x9283;&#x8CEA;&#x91CF;&#x5206;&#x6790;&#x30E1;&#x30BD;&#x30C3;&#x30C9;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x307E;&#x3059;&#x3002;&#x7D30;&#x80DE;&#x9AA8;&#x683C;&#x86CB;&#x767D;&#x8CEA;&#x306B;&#x52A0;&#x3048;&#x3066;&#x3001;&#x30AB;&#x30EB;&#x30B7;&#x30A6;&#x30E0;&#x8ABF;&#x7BC0;&#x306B;&#x95A2;&#x4E0E;&#x3059;&#x308B;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x304A;&#x3088;&#x3073;&#x30B9;&#x30C8;&#x30EC;&#x30B9;&#x5FDC;&#x7B54;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x8CEA;&#x91CF;&#x5206;&#x6790;&#x6CD5;&#x306B;&#x3088;&#x308B;&#x540C;&#x5B9A;&#x3055;&#x308C;&#x305F;&#x6700;&#x3082;&#x8C4A;&#x5BCC;&#x306A;&#x30D0;&#x30F3;&#x30C9;&#x30EB; &#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x306E;&#x591A;&#x304F;&#x306E; ATP &#x5408;&#x6210;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x305F;&#x3002;&#x30D9;&#x30FC;&#x30BF; &#x30A2;&#x30AF;&#x30C1;&#x30F3;&#x5F8C;&#x30AF;&#x30EC;&#x30A2;&#x30C1;&#x30F3;&#x30AD;&#x30CA;&#x30FC;&#x30BC;&#x306E;&#x30BE;&#x30EB;&#x6027;&#x7D30;&#x80DE;&#x8CEA;&#x306E;&#x8133;&#x30A2;&#x30A4;&#x30BD; &#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x306F;&#x6B21;&#x306E;&#x6700;&#x3082;&#x8C4A;&#x5BCC;&#x306A;&#x30D0;&#x30F3;&#x30C9;&#x30EB;&#x86CB;&#x767D;&#x8CEA;&#x3060;&#x3063;&#x305F;;&#x7D04; 0.5 mM &#x3067;&#x30AF;&#x30EC;&#x30A2;&#x30C1;&#x30F3;&#x30AD;&#x30CA;&#x30FC;&#x30BC;&#x9AD8;&#x306E; ATP &#x30EC;&#x30D9;&#x30EB; 1 mM/s ATP &#x6D88;&#x8CBB;&#x306B;&#x3088;&#x3063;&#x3066;&#x7D30;&#x80DE;&#x819C;&#x306E; Ca(2+) ATPase &#x306B;&#x3082;&#x304B;&#x304B;&#x308F;&#x3089;&#x305A;&#x7DAD;&#x6301;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x4E00;&#x8CAB;&#x6027;&#x306E;&#x3042;&#x308B;&#x3053;&#x306E;&#x9AEA;&#x675F;&#x95A2;&#x6570;&#x3067;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x306F;&#x3001;&#x30AF;&#x30EC;&#x30A2;&#x30C1;&#x30F3;&#x30AD;&#x30CA;&#x30FC;&#x30BC;&#x56DE;&#x8DEF;&#x306F;&#x9AD8;&#x611F;&#x5EA6;&#x30AF;&#x30EC;&#x30A2;&#x30C1;&#x30F3;&#x30AD;&#x30CA;&#x30FC;&#x30BC; &#x30CE;&#x30C3;&#x30AF;&#x30A2;&#x30A6;&#x30C8; &#x30DE;&#x30A6;&#x30B9;&#x306E;&#x96E3;&#x8074;&#x3067;&#x793A;&#x3057;&#x305F;&#x3088;&#x3046;&#x306B;&#x805E;&#x304F;&#x305F;&#x3081;&#x306B;&#x4E0D;&#x53EF;&#x6B20;&#x3067;&#x3059;&#x3002;

&#x9AEA;&#x675F; ATP &#x914D;&#x4FE1;&#x3092;&#x4ECB;&#x3057;&#x3066;&#x30AF;&#x30EC;&#x30A2;&#x30C1;&#x30F3;&#x30AD;&#x30CA;&#x30FC;&#x30BC;&#x3092;&#x5C02;&#x9580;&#x306B;&#x3057;&#x307E;&#x3059;&#x3002;

&#xAC15;&#xB825; &#xD558; &#xAC8C;, &#xBA38;&#xB9AC; &#xC138;&#xD3EC;&#xC758; &#xAE30;&#xACC4;&#xC801;&#xC73C;&#xB85C; &#xC790;&#xADF9; &#xD558;&#xB294; &#xACBD;&#xC6B0; &#xBBFC;&#xAC10;&#xD55C; &#xBC88;&#xB4E4; &#xC0AC;&#xC6A9;&#xD560; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4; ATP &#xB108;&#xBB34; &#xAE09;&#xC18D; &#xD558; &#xAC8C; &#xBCF4;&#xAE09;&#xC5D0; &#xB300; &#xD55C; &#xD655;&#xC0B0;&#xC5D0; &#xC758;&#xD574;. &#xBC88;&#xB4E4;&#xC758; &#xB2E8;&#xBC31;&#xC9C8; &#xBCF4;&#xCDA9;, &#xC5D0;&#xB108;&#xC9C0; &#xB300;&#xC0AC;&#xC5D0; &#xCC38;&#xC5EC; &#xD558;&#xB294; &#xADF8; &#xB2E8;&#xBC31;&#xC9C8;&#xC744; &#xD3EC;&#xD568; &#xD558; &#xC5EC; &#xAD11;&#xBC94;&#xC704; &#xD55C; &#xBCF4;&#xAE30;&#xB97C; &#xC81C;&#xACF5; &#xD558;&#xB3C4;&#xB85D; &#xC21C;&#xD654; &#xB41C; &#xB2ED; vestibular &#xBC88;&#xB4E4;&#xC758; &#xB2E8;&#xBC31;&#xC9C8;&#xC744; &#xC2DD;&#xBCC4; &#xD558; &#xC0F7;&#xAC74; &#xC9C8;&#xB7C9; &#xBD84;&#xC11D; &#xBC29;&#xBC95;&#xC744; &#xC0AC;&#xC6A9; &#xD588;&#xC2B5;&#xB2C8;&#xB2E4;. Cytoskeletal &#xB2E8;&#xBC31;&#xC9C8;, &#xB2E8;&#xBC31;&#xC9C8;&#xACFC; Ca(2+) &#xADDC;&#xC815;&#xC5D0; &#xAD00;&#xB828; &#xB41C; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4; &#xB300;&#xC751; &#xB2E8;&#xBC31;&#xC9C8; &#xC774;&#xC678;&#xC5D0; &#xAC00;&#xC7A5; &#xD48D;&#xBD80;&#xD55C; &#xBC88;&#xB4E4; &#xB2E8;&#xBC31;&#xC9C8; &#xC9C8;&#xB7C9; &#xBD84;&#xC11D;&#xC5D0; &#xC758;&#xD574; &#xD655;&#xC778; &#xB41C; &#xADF8;&#xC758; &#xB9CE;&#xC740; ATP &#xD569;&#xC131;&#xC5D0; &#xCC38;&#xC5EC; &#xD588;&#xB2E4;. &#xBCA0;&#xD0C0; &#xB9D0;&#xB77C; &#xD6C4; creatine kinase&#xC758; cytosolic &#xB1CC; isoform&#xB294; &#xB2E4;&#xC74C; &#xAC00;&#xC7A5; &#xD48D;&#xBD80;&#xD55C; &#xBC88;&#xB4E4; &#xB2E8;&#xBC31;&#xC9C8;; &#xC57D; 0.5 m m, creatine kinase &#xD50C;&#xB77C;&#xC988;&#xB9C8; &#xBA64;&#xBE0C;&#xB808;&#xC778; Ca(2+) Atpase&#xC5D0; &#xC758;&#xD574; 1 mM/s ATP &#xC18C;&#xBE44;&#xC5D0;&#xB3C4; &#xBD88;&#xAD6C; &#xD558; &#xACE0; &#xB192;&#xC740; ATP &#xB808;&#xBCA8;&#xC744; &#xC720;&#xC9C0; &#xAC00;&#xB2A5; &#xD558;&#xB2E4;. &#xBA38;&#xB9AC; &#xBC88;&#xB4E4; &#xAE30;&#xB2A5;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC774; &#xC77C;&#xCE58;, creatine kinase &#xD68C;&#xB85C; &#xACE0;&#xAC10;&#xB3C4; &#xB09C;&#xCCAD; creatine kinase &#xB179;&#xC544;&#xC6C3; &#xC950;&#xC5D0; &#xC758;&#xD574; &#xC99D;&#xBA85;&#xC73C;&#xB85C; &#xCCAD;&#xAC01;&#xC744; &#xC704;&#xD574; &#xD544;&#xC218;&#xC801; &#xC774;&#xB2E4;.

&#xBA38;&#xB9AC; &#xBB36;&#xC74C; creatine kinase&#xB97C; &#xD1B5;&#xD574; ATP &#xBC30;&#xB2EC; &#xC804;&#xBB38;.

Cuando estimulan fuertemente, de una c&eacute;lula de pelo mec&aacute;nicamente paquete de cabello sensible puede consumir ATP demasiado r&aacute;pido para reposici&oacute;n por difusi&oacute;n. Para proporcionar una visi&oacute;n amplia del complemento de prote&iacute;na del paquete, incluyendo aquellas prote&iacute;nas que participan en el metabolismo energ&eacute;tico, se utilizaron m&eacute;todos de espectrometr&iacute;a de masas de escopeta para identificar prote&iacute;nas de paquetes vestibular pollo purificado. Adem&aacute;s de prote&iacute;nas citoesquel&eacute;ticas, prote&iacute;nas implicadas en la regulaci&oacute;n de la CA y prote&iacute;nas de respuesta al estr&eacute;s, muchas de las prote&iacute;nas m&aacute;s abundantes del paquete que fueron identificadas por espectrometr&iacute;a de masas estuvieron implicados en la s&iacute;ntesis de ATP. Despu&eacute;s de beta-actina, la isoforma cerebro citos&oacute;lica de la cinasa de la creatina fue la siguiente prote&iacute;na m&aacute;s abundante de paquete; en aproximadamente 0,5 mM, cinasa de la creatina es capaz de mantener altos niveles de ATP, a pesar de consumo de 1 mM/s ATP por el Ca(2+)-ATPasa de la membrana plasm&aacute;tica. Consistente con este papel fundamental en la funci&oacute;n del paquete de pelo, el circuito de la cinasa de la creatina es esencial para la alta sensibilidad auditiva seg&uacute;n lo demostrado por la p&eacute;rdida de la audici&oacute;n en ratones knockout de cinasa de la creatina.

Paquetes del pelo se especializan para la entrega de la ATP a trav&eacute;s de cinasa de la creatina.

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.

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.

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.

Article	Year
The European journal of neuroscience\| PubMed ID: 12059977	2002
Molecular and cellular biochemistry\| PubMed ID: 14977190	2004
Behavioural brain research\| PubMed ID: 15302123	2004
Behavioural brain research\| PubMed ID: 15639173	2005
Hair bundles are specialized for ATP delivery via creatine kinase. Neuron\| PubMed ID: 17270734	2007
Dietary restriction started after spinal cord injury improves functional recovery. Experimental neurology\| PubMed ID: 18585708	2008
Physiology & behavior\| PubMed ID: 19419668	2009
Epilepsia\| PubMed ID: 19624717	2010
Lack of neuroprotective effects of simvastatin and minocycline in a model of cervical spinal cord injury. Experimental neurology\| PubMed ID: 20599974	2010
Intermittent fasting improves functional recovery after rat thoracic contusion spinal cord injury. Journal of neurotrauma\| PubMed ID: 21219083	2011
Journal of neurotrauma\| PubMed ID: 21410319	2011
Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats. PloS one\| PubMed ID: 21559420	2011

Femke Streijger

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