calibrated-forceps-model-of-spinal-cord-compression-injury

Calibrated Forceps Model of Spinal Cord Compression Injury

Compression injuries of the murine spinal cord are valuable animal models for the study of spinal cord injury (SCI) and spinal regenerative therapy. The ...

University of California, Davis

Shriners Hospitals for Children (Northern California)

The distribution and relative intrafascicular contribution of myelin fibers derived from spinal segments L-4 to L-6 were analyzed in adult rat sciatic nerve and its main branches, using 200-kDa neurofilament subunit immunodetection in previously injured nerve sections in the L-4 or L-5 spinal branch or both. These branches' functional contribution was evaluated 16 days after the injury, using the method of J. Bain, S. Mackinnon, and D. Hunter (1988, Plast. Reconstr. Surg. 83: 129-136). A common topographic intrafascicular distribution was found in 69% of cases, with notable segregation of L-4 and L-5 fibers and a random distribution for L-6 fibers. At sciatic nerve main branch level, L-4 contributes almost entirely to the peroneal nerve, L-5 to the tibial nerve, and L-6 and other branches to the sural nerve. After injury to L-4, a significant reduction in peroneal nerve functional index (PFI) was observed, as was a reduction in print length (PL). Injury to L-5 caused a significant reduction in the sciatic (SFI) and tibial (TFI) functional nerve indices, an increase in PL, and a reduction in the spread between opposite toes (TS). Finally, transection of both L-4 and L-5 was followed by a significant reduction in all functional indices measured, an increase in PL, and a reduction in intermediate toe (ITS) and opposite toe spread (TS). The results indicate a direct relationship between the distribution and contribution of the spinal nerve fibers forming the sciatic nerve and the alteration in functional indices for sciatic, tibial, and peroneal nerves.

Relationship between functional deficiencies and the contribution of myelin nerve fibers derived from L-4, L-5, and L-6 spinolumbar branches in adult rat sciatic nerve.

&#x6211;&#x4EEC;&#x8C03;&#x67E5;&#x4E86;&#x4E00;&#x9879;&#x6218;&#x7565;&#xFF0C;&#x6539;&#x5584;&#x7535;&#x673A;&#x6536;&#x5230; 6-&#x7F9F;&#x57FA;&#x591A;&#x5DF4;&#x80FA; (6-OHDA) &#x75C5;&#x53D8;&#x3001; &#x5E15;&#x91D1;&#x68EE;&#x75C5;&#xFF0C;&#x901A;&#x8FC7;&#x80DA;&#x80CE;&#x5185;&#x4FA7;&#x795E;&#x7ECF;&#x8282;&#x9686;&#x8D77; (MGE) &#x7EC6;&#x80DE;&#x79FB;&#x690D;&#x5165;&#x7EB9;&#x72B6;&#x4F53;&#x7684;&#x556E;&#x9F7F;&#x52A8;&#x7269;&#x6A21;&#x578B;&#x7684;&#x5927;&#x9F20;&#x7684;&#x75C7;&#x72B6;&#x3002;&#x5927;&#x8111;&#x53D1;&#x5C55;&#x8FC7;&#x7A0B;&#x4E2D;&#xFF0C;&#x80DA;&#x80CE; MGE &#x7EC6;&#x80DE;&#x8FC1;&#x79FB;&#x5230;&#x7EB9;&#x72B6;&#x4F53;&#x548C;&#x5927;&#x8111;&#x76AE;&#x5C42;&#xFF0C;&#x4ED6;&#x4EEC;&#x5230;&#x5B89;&#x57FA; interneurons &#x6210;&#x719F;&#x5E76;&#x53D1;&#x6325;&#x5173;&#x952E;&#x4F5C;&#x7528;&#xFF0C;&#x5EFA;&#x7ACB;&#x6FC0;&#x52B1;&#x548C;&#x6291;&#x5236;&#x7684;&#x5E73;&#x8861;&#x3002;&#x4E0D;&#x540C;&#x4E8E;&#x5927;&#x591A;&#x6570;&#x5176;&#x4ED6;&#x80DA;&#x80CE;&#x7684;&#x795E;&#x7ECF;&#x5143;&#xFF0C;MGE &#x5355;&#x5143;&#x683C;&#x4FDD;&#x7559;&#x8FC1;&#x79FB;&#x548C;&#x6574;&#x5408;&#x65F6;&#x4EA7;&#x540E;&#x548C;&#x6210;&#x4EBA;&#x8111;&#x5185;&#x79FB;&#x690D;&#x7684;&#x80FD;&#x529B;&#x3002;&#x6211;&#x4EEC;&#x6267;&#x884C;&#x63A7;&#x5236;&#x548C; 6-&#x7F9F;&#x57FA;&#x591A;&#x5DF4;&#x80FA;&#x5927;&#x9F20;&#x57FA;&#x5E95;&#x8282;&#x5230; MGE &#x7EC6;&#x80DE;&#x7684;&#x79FB;&#x690D;&#x3002;MGE &#x7EC6;&#x80DE;&#x79FB;&#x690D;&#x5E78;&#x5B58;&#x4E0B;&#x6765;&#x3001; &#x8BF1;&#x5BFC;&#x5206;&#x5316;&#x4E3A;&#x795E;&#x7ECF;&#x7EC6;&#x80DE; GABA(+)&#x3001; &#x96C6;&#x6210;&#x5230;&#x4E3B;&#x673A;&#x7535;&#x8DEF;&#x548C;&#x4FEE;&#x6539;&#x4E24;&#x79CD;&#x5DF4;&#x80FA;&#x8FD0;&#x52A8;&#x884C;&#x4E3A;&#x548C;&#x63A7;&#x5236;&#x5927;&#x9F20;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x6570;&#x636E;&#x8868;&#x660E; MGE &#x7EC6;&#x80DE;&#x79FB;&#x690D;&#x5165;&#x7EB9;&#x72B6;&#x4F53;&#x662F;&#x6709;&#x524D;&#x9014;&#x7684;&#x65B9;&#x6CD5;&#xFF0C;&#x8C03;&#x67E5;&#x91CD;&#x5851;&#x57FA;&#x5E95;&#x8282;&#x7535;&#x8DEF;&#x5728;&#x795E;&#x7ECF;&#x9000;&#x884C;&#x6027;&#x75BE;&#x75C5;&#x7684;&#x6F5C;&#x5728;&#x597D;&#x5904;&#x3002;

MGE &#x4F53;&#x7EC6;&#x80DE;&#x80DA;&#x80CE;&#x79FB;&#x690D;&#x5230;&#x6210;&#x5E74;&#x5927;&#x9F20;&#x7EB9;&#x72B6;&#x4F53;&#x96C6;&#x6210;&#x548C;&#x6539;&#x5584;&#x7535;&#x673A; 6-&#x7F9F;&#x57FA;&#x591A;&#x5DF4;&#x80FA;&#x5927;&#x9F20;&#x7684;&#x75C7;&#x72B6;&#x3002;

We investigated a strategy to ameliorate the motor symptoms of rats that received 6-hydroxydopamine (6-OHDA) lesions, a rodent model of Parkinson's disease, through transplantation of embryonic medial ganglionic eminence (MGE) cells into the striatum. During brain development, embryonic MGE cells migrate into the striatum and neocortex where they mature into GABAergic interneurons and play a key role in establishing the balance between excitation and inhibition. Unlike most other embryonic neurons, MGE cells retain the capacity for migration and integration when transplanted into the postnatal and adult brain. We performed MGE cell transplantation into the basal ganglia of control and 6-OHDA-lesioned rats. Transplanted MGE cells survived, differentiated into GABA(+) neurons, integrated into host circuitry, and modified motor behavior in both lesioned and control rats. Our data suggest that MGE cell transplantation into the striatum is a promising approach to investigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases.

Embryonic MGE precursor cells grafted into adult rat striatum integrate and ameliorate motor symptoms in 6-OHDA-lesioned rats.

Nous avons &#xE9;tudi&#xE9; une strat&#xE9;gie pour am&#xE9;liorer les sympt&#xF4;mes moteurs de rats qui ont re&#xE7;u 6-hydroxydopamine (6-OHDA) des l&#xE9;sions, un mod&#xE8;le rongeur de la maladie de Parkinson, par la transplantation d&#x26;#39;embryons m&#xE9;diale ganglionnaires Eminence (MGE) des cellules dans le striatum. Pendant le d&#xE9;veloppement du cerveau, les cellules embryonnaires MGE migrer dans le striatum et le n&#xE9;ocortex o&#xF9; elles se d&#xE9;veloppent dans les interneurones GABAergiques et jouent un r&#xF4;le cl&#xE9; dans l&#x26;#39;&#xE9;tablissement de l&#x26;#39;&#xE9;quilibre entre excitation et inhibition. Contrairement &#xE0; la plupart des autres neurones embryonnaires, les cellules MGE conserver la capacit&#xE9; de la migration et l&#x26;#39;int&#xE9;gration lorsqu&#x26;#39;elles sont transplant&#xE9;es dans le cerveau postnatal et adulte. Nous avons effectu&#xE9; la transplantation de cellules MGE dans les noyaux gris centraux de contr&#xF4;le et de 6-OHDA-l&#xE9;s&#xE9;s rats. Cellules transplant&#xE9;es ont surv&#xE9;cu MGE, diff&#xE9;renci&#xE9;es en GABA (+) neurones, int&#xE9;gr&#xE9; dans un circuit d&#x26;#39;accueil, et modifi&#xE9; le comportement moteur chez les rats l&#xE9;s&#xE9;s et de contr&#xF4;le. Nos donn&#xE9;es sugg&#xE8;rent que la transplantation de cellules MGE dans le striatum est une approche prometteuse pour &#xE9;tudier les avantages potentiels de remodelage des circuits des noyaux gris centraux dans les maladies neurod&#xE9;g&#xE9;n&#xE9;ratives.

Cellules embryonnaires pr&#xE9;curseurs MGE greff&#xE9;es dans le striatum du rat adulte Int&#xE9;grer et am&#xE9;liorer les sympt&#xF4;mes moteurs de la 6-OHDA-l&#xE9;s&#xE9;s Rats

Wir untersuchten eine Strategie, um die motorische Symptome von Ratten zu lindern, die 6-Hydroxydopamine (6-OHDA) L&auml;sionen, ein Nagetier Modell der Parkinson-Krankheit durch Transplantation embryonaler medialen Lymphom Eminenz (MGE) Zellen in Striatum empfangen. W&auml;hrend der Entwicklung des Gehirns migrieren die embryonale Zellen in MGE in das Striatum und der Gro&szlig;hirnrinde, wo sie &auml;ltere in GABAergic Interneuronen und spielen eine Schl&uuml;sselrolle bei der Festlegung der Balance zwischen Erregung und Hemmung. Im Gegensatz zu den meisten anderen embryonalen Neuronen behalten MGE Zellen die F&auml;higkeit zur Migration und Integration, wenn in der postnatalen und adulten Gehirn transplantiert. Wir spielten MGE Stammzelltransplantation in den Basalganglien Kontroll-und 6-OHDA-lesioned Ratten. Transplantierte MGE Zellen &uuml;berlebten, unterschieden in GABA(+) Neuronen, in Host-Schaltung integriert und motor Verhalten in beiden lesioned ge&auml;ndert und Ratten zu steuern. Unsere Daten zeigen, dass die Transplantation von MGE in Striatum ist ein vielversprechender Ansatz, um die potenziellen Vorteile der Umgestaltung der Basalganglien-Schaltung bei neurodegenerativen Krankheiten zu untersuchen.

Embryonale MGE-Vorl&auml;uferzellen, die in Erwachsene Ratte Striatum eingepfropft integrieren und motorische Symptome bei 6-OHDA-lesioned Ratten zu lindern.

Abbiamo studiato una strategia per migliorare i sintomi motori di ratti che hanno ricevuto lesioni 6-hydroxydopamine (6-OHDA), un modello di roditore del morbo di Parkinson, attraverso il trapianto di cellule embrionali eminenza ganglionica mediale (MGE) nello striato. Durante lo sviluppo del cervello, le cellule embrionali MGE migrano nel corpo striato e neocorteccia dove maturano in GABAergic interneurons e gioca un ruolo chiave nello stabilire l&#39;equilibrio tra eccitazione e inibizione. A differenza della maggior parte degli altri neuroni embrionali, cellule MGE conservano la capacit&agrave; di migrazione e integrazione quando trapiantato nel cervello adulto e postnatale. Abbiamo eseguito il trapianto di cellule MGE in gangli basali del controllo e 6-OHDA-elettivamente ratti. Cellule trapiantate MGE sopravvissero, differenziano in neuroni GABA(+), integrato nel circuito di host e modificato il comportamento del motore in entrambi elettivamente e ratti di controllo. I nostri dati suggeriscono che il trapianto di cellule MGE nello striato &egrave; un promettente approccio per investigare i benefici potenziali di rimodellamento dei circuiti dei gangli della base nelle malattie neurodegenerative.

MGE precursori embrionali innestati nel corpo striato di ratto adulto integrano e migliorare i sintomi motori nei ratti 6-OHDA-elettivamente.

&#x6211;&#x3005;&#x306F;&#x3001;&#x7DDA;&#x6761;&#x4F53;&#x306B;&#x80DA;&#x5185;&#x5074;&#x795E;&#x7D4C;&#x7BC0;&#x9686;&#x8D77;&#xFF08;MGE&#xFF09;&#x7D30;&#x80DE;&#x306E;&#x79FB;&#x690D;&#x306B;&#x3088;&#x3063;&#x3066;6  - &#x30D2;&#x30C9;&#x30ED;&#x30AD;&#x30B7;&#xFF08;6-OHDA&#xFF09;&#x75C5;&#x5909;&#x3001;&#x30D1;&#x30FC;&#x30AD;&#x30F3;&#x30BD;&#x30F3;&#x75C5;&#x306E;&#x9F67;&#x6B6F;&#x985E;&#x30E2;&#x30C7;&#x30EB;&#x3092;&#x3001;&#x53D7;&#x4FE1;&#x3057;&#x305F;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x904B;&#x52D5;&#x75C7;&#x72B6;&#x3092;&#x6539;&#x5584;&#x3059;&#x308B;&#x305F;&#x3081;&#x306E;&#x6226;&#x7565;&#x3092;&#x691C;&#x8A0E;&#x3057;&#x305F;&#x3002;&#x8133;&#x306E;&#x767A;&#x9054;&#x306E;&#x9593;&#x306B;&#x3001;&#x80DA;&#x306E;MGE&#x7D30;&#x80DE;&#x306F;&#x3001;GABA&#x4F5C;&#x52D5;&#x6027;&#x4ECB;&#x5728;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x306B;&#x6210;&#x719F;&#x3057;&#x3001;&#x8208;&#x596E;&#x3068;&#x6291;&#x5236;&#x306E;&#x30D0;&#x30E9;&#x30F3;&#x30B9;&#x3092;&#x78BA;&#x7ACB;&#x3059;&#x308B;&#x4E0A;&#x3067;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3057;&#x3066;&#x7DDA;&#x6761;&#x4F53;&#x3068;&#x76AE;&#x8CEA;&#x306B;&#x79FB;&#x884C;&#x3059;&#x308B;&#x3002;&#x751F;&#x5F8C;&#x304A;&#x3088;&#x3073;&#x6210;&#x4F53;&#x8133;&#x306B;&#x79FB;&#x690D;&#x3057;&#x305F;&#x3068;&#x304D;&#x306B;&#x3001;&#x4ED6;&#x306E;&#x307B;&#x3068;&#x3093;&#x3069;&#x306E;&#x80DA;&#x6027;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x3068;&#x306F;&#x7570;&#x306A;&#x308A;&#x3001;MGE&#x7D30;&#x80DE;&#x304C;&#x79FB;&#x884C;&#x3068;&#x7D71;&#x5408;&#x306E;&#x305F;&#x3081;&#x306E;&#x80FD;&#x529B;&#x3092;&#x4FDD;&#x6301;&#x3057;&#x307E;&#x3059;&#x3002;&#x6211;&#x3005;&#x306F;&#x3001;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x3068;6-OHDA-&#x7834;&#x58CA;&#x30E9;&#x30C3;&#x30C8;&#x306E;&#x5927;&#x8133;&#x57FA;&#x5E95;&#x6838;&#x306B;MGE&#x7D30;&#x80DE;&#x79FB;&#x690D;&#x3092;&#x884C;&#x3063;&#x305F;&#x3002;&#x79FB;&#x690D;MGE&#x7D30;&#x80DE;&#x306F;&#x3001;&#x5BBF;&#x4E3B;&#x306E;&#x56DE;&#x8DEF;&#x306B;&#x7D44;&#x307F;&#x8FBC;&#x307E;GABA&#xFF08;+&#xFF09;&#x30CB;&#x30E5;&#x30FC;&#x30ED;&#x30F3;&#x3001;&#x304A;&#x3088;&#x3073;&#x75C5;&#x5909;&#x3068;&#x30B3;&#x30F3;&#x30C8;&#x30ED;&#x30FC;&#x30EB;&#x306E;&#x4E21;&#x65B9;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x5909;&#x66F4;&#x3055;&#x308C;&#x305F;&#x30E2;&#x30FC;&#x30BF;&#x306E;&#x52D5;&#x4F5C;&#x306B;&#x5206;&#x5316;&#x3057;&#x3001;&#x751F;&#x304D;&#x6B8B;&#x3063;&#x305F;&#x3002;&#x6211;&#x3005;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x3001;&#x7DDA;&#x6761;&#x4F53;&#x306B;MGE&#x7D30;&#x80DE;&#x79FB;&#x690D;&#x306F;&#x3001;&#x795E;&#x7D4C;&#x5909;&#x6027;&#x75BE;&#x60A3;&#x306B;&#x304A;&#x3051;&#x308B;&#x5927;&#x8133;&#x57FA;&#x5E95;&#x6838;&#x56DE;&#x8DEF;&#x3092;&#x6539;&#x9020;&#x306E;&#x6F5C;&#x5728;&#x7684;&#x306A;&#x5229;&#x70B9;&#x3092;&#x8ABF;&#x67FB;&#x3059;&#x308B;&#x305F;&#x3081;&#x306E;&#x6709;&#x671B;&#x306A;&#x30A2;&#x30D7;&#x30ED;&#x30FC;&#x30C1;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;

&#x5927;&#x4EBA;&#x306E;&#x30E9;&#x30C3;&#x30C8;&#x7DDA;&#x6761;&#x4F53;&#x306B;&#x79FB;&#x690D;&#x80DA;&#x306E;MGE&#x306E;&#x524D;&#x99C6;&#x7D30;&#x80DE;&#x306F;6-OHDA-&#x75C5;&#x5909;&#x30E9;&#x30C3;&#x30C8;&#x306B;&#x304A;&#x3051;&#x308B;&#x904B;&#x52D5;&#x75C7;&#x72B6;&#x3092;&#x7D71;&#x5408;&#x3057;&#x3001;&#x6539;&#x5584;&#x3059;&#x308B;

&#xC6B0;&#xB9AC;&#xAC00; &#xBC1B;&#xC740; 6-hydroxydopamine (6-OHDA) &#xBCD1; &#xBCC0;, &#xACE0;&#xAC00;&#xC5D0; &#xC911;&#xAC04; ganglionic &#xC608; &#xD558; &#xBBF8; &#xBC1C;&#xB2EC; (MGE) &#xC138;&#xD3EC;&#xC758; &#xC774;&#xC2DD; &#xD1B5;&#xD574; &#xD30C; &#xD0A8; &#xC2A8; &#xBCD1;&#xC758; &#xC124;&#xCE58;&#xB958; &#xBAA8;&#xB378; &#xC950;&#xC758; &#xBAA8;&#xD130; &#xC99D;&#xC0C1;&#xC744; &#xAC1C;&#xB7C9; &#xD558;&#xB294; &#xC804;&#xB7B5;&#xC744; &#xC870;&#xC0AC;. &#xB450;&#xB1CC; &#xAC1C;&#xBC1C; &#xD558;&#xB294; &#xB3D9;&#xC548; &#xBC30;&#xC544; MGE &#xC138;&#xD3EC;&#xAC00; &#xD14D; &#xADF8;&#xB4E4;&#xC740; GABAergic &#xC218;&#xB85C; &#xC131;&#xC219; &#xD558; &#xACE0; &#xC5EC;&#xAE30;&#xC640; &#xC5B5;&#xC81C; &#xC0AC;&#xC774;&#xC758; &#xADE0;&#xD615;&#xC744; &#xC218;&#xB9BD;&#xC5D0; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC5D0; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158;&#xD569;&#xB2C8;&#xB2E4;. &#xB300;&#xBD80;&#xBD84;&#xC758; &#xB2E4;&#xB978; &#xBC30;&#xC544; &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xC640; &#xB2EC;&#xB9AC; MGE &#xC140; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158; &#xBC0F; &#xD1B5;&#xD569; &#xC131;&#xC778; &#xCD9C;&#xC0DD; &#xD6C4; &#xB1CC;&#xC5D0; &#xC774;&#xC2DD; &#xD558;&#xB294; &#xACBD;&#xC6B0;&#xC5D0; &#xB300; &#xD55C; &#xC6A9;&#xB7C9;&#xC744; &#xC720;&#xC9C0; &#xD569;&#xB2C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC81C;&#xC5B4; &#xBC0F; 6-OHDA-lesioned &#xC950;&#xC758; &#xAE30;&#xCD08; &#xC911;&#xCD94;&#xB85C; MGE &#xC138;&#xD3EC;&#xAC00; &#xC2DD;&#xC740; &#xC218;&#xD589;. &#xC774;&#xC2DD;&#xB41C; MGE &#xC140; &#xC0B4;&#xC544;&#xB0A8;&#xC740;, GABA(+) &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xB85C; &#xBD84;&#xD654;, &#xD638;&#xC2A4;&#xD2B8; &#xD68C;&#xB85C;&#xC5D0; &#xD1B5;&#xD569; &#xD558; &#xACE0; &#xBAA8;&#xB450; lesioned&#xC5D0;&#xC11C; &#xBAA8;&#xD130; &#xB3D9;&#xC791; &#xC218;&#xC815; &#xBC0F; &#xC950; &#xC81C;&#xC5B4;. &#xC6B0;&#xB9AC;&#xC758; &#xB370;&#xC774;&#xD130; MGE &#xC138;&#xD3EC; &#xC774;&#xC2DD;&#xC5D0;&#xB294; &#xC2E0;&#xACBD; &#xD1F4;&#xD589; &#xC131; &#xC9C8;&#xD658;&#xC758; &#xAE30;&#xCD08; &#xC911;&#xCD94; &#xD68C;&#xB85C; &#xAC1C;&#xC7A5;&#xC758; &#xC7A0;&#xC7AC;&#xC801;&#xC778; &#xC774;&#xB4DD;&#xC744; &#xC870;&#xC0AC; &#xD558;&#xB294; &#xC720;&#xB9DD;&#xD55C; &#xC811;&#xADFC; &#xAC83;&#xC774; &#xC88B;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC131;&#xC778; &#xC950;&#xAC00; &#xD22C;&#xC785; &#xBC30;&#xC544; MGE &#xC804;&#xC870; &#xC138;&#xD3EC; &#xD1B5;&#xD569; &#xD558; &#xACE0; 6-OHDA-lesioned &#xC950; &#xBAA8;&#xD130; &#xC99D;&#xC0C1; &#xAC1C;&#xC120;.

Se investig&#xF3; una estrategia para mejorar los s&#xED;ntomas motores de las ratas que recibieron 6-hidroxidopamina (6-OHDA) lesiones, un modelo animal de enfermedad de Parkinson, a trav&#xE9;s del trasplante de embriones medial ganglionares Eminencia (MGE), las c&#xE9;lulas en el cuerpo estriado. Durante el desarrollo del cerebro, las c&#xE9;lulas embrionarias MGE migrar hacia el cuerpo estriado y la corteza cerebral, donde maduran en interneuronas GABA&#xE9;rgicas y jugar un papel clave en el establecimiento del equilibrio entre la excitaci&#xF3;n y la inhibici&#xF3;n. A diferencia de la mayor&#xED;a de las neuronas embrionarias de otro modo, las c&#xE9;lulas conservan la capacidad de MGE para la migraci&#xF3;n y la integraci&#xF3;n cuando se trasplantan en el cerebro postnatal y adulto. Se realiz&#xF3; el trasplante de c&#xE9;lulas de MGE en los ganglios basales de control y las ratas 6-OHDA lesionadas. Las c&#xE9;lulas trasplantadas sobrevivieron MGE, diferenciados en GABA (+) las neuronas, integrado en los circuitos de acogida, y modificar la conducta motora en ratas lesionadas tanto y control. Nuestros datos sugieren que el trasplante de c&#xE9;lulas de MGE en el cuerpo estriado es un enfoque prometedor para investigar los beneficios potenciales de la remodelaci&#xF3;n de circuitos de los ganglios basales en las enfermedades neurodegenerativas.

C&#xE9;lulas precursoras embrionarias MGE injertadas en estriado de rata adulto Integrar y mejorar los s&#xED;ntomas motores en la 6-OHDA ratas lesionadas

Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypical behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.

Embryonic intraventricular exposure to autism-specific maternal autoantibodies produces alterations in autistic-like stereotypical behaviors in offspring mice.

Reelin protein (RELN) level is reduced in the cerebral cortex and cerebellum of subjects with autism. RELN is synthesized and secreted by a subpopulation of neurons in the developing cerebral cortex termed Cajal-Retzius (CR) cells. These cells are abundant in the marginal zone during cortical development, many die after development is complete, but a small population persists into adulthood. In adult brains, RELN is secreted by the surviving CR cells, by a subset of GABAergic interneurons in layer I, and by pyramidal cells and GABAergic interneurons in deeper cortical layers. It is widely believed that decreased RELN in layer I of the cerebral cortex of subjects with autism may result from a decrease in the density of RELN expressing neurons in layer I; however, this hypothesis has not been tested. We examined RELN expression in layer I of the adult human cortex and found that 70% of cells express RELN in both control and autistic subjects. We quantified the density of neurons in layer I of the superior temporal cortex of subjects with autism and age-matched control subjects. Our data show that there is no change in the density of neurons in layer I of the cortex of subjects with autism, and therefore suggest that reduced RELN expression in the cerebral cortex of subjects with autism is not a consequence of decreased numbers of RELN-expressing neurons in layer I. Instead reduced RELN may result from abnormal RELN processing, or a decrease in the number of other RELN-expressing neuronal cell types.

RELN-expressing neuron density in layer I of the superior temporal lobe is similar in human brains with autism and in age-matched controls.

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene that is characterized by progressive action tremor, gait ataxia, and cognitive decline. Recent studies of mitochondrial dysfunction in FXTAS have suggested that iron dysregulation may be one component of disease pathogenesis. We tested the hypothesis that iron dysregulation is part of the pathogenic process in FXTAS. We analyzed postmortem choroid plexus from FXTAS and control subjects, and found that in FXTAS iron accumulated in the stroma, transferrin levels were decreased in the epithelial cells, and transferrin receptor 1 distribution was shifted from the basolateral membrane (control) to a predominantly intracellular location (FXTAS). In addition, ferroportin and ceruloplasmin were markedly decreased within the epithelial cells. These alterations have implications not only for understanding the pathophysiology of FXTAS, but also for the development of new clinical treatments that may incorporate selective iron chelation.

Dysregulated iron metabolism in the choroid plexus in fragile X-associated tremor/ataxia syndrome.

Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased cellular proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size also and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.

Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

We investigated the cytoarchitecture of the anterior superior temporal area (TA2) of the postmortem cerebral cortex in 9 subjects with autism and 9 age-matched typically developing subjects between the ages of 13 and 56 years. The superior temporal gyrus is involved in auditory processing and social cognition and its pathology has been correlated with autism. We quantified the number and soma volume of pyramidal neurons in the supragranular layers and pyramidal neurons in the infragranular layers in each subject. We did not find significant differences in the number or volume of supragranular or infragranular neurons in the cerebral cortex of subjects with autism compared to typically developing subjects. This report does not support an alteration of supragranular to infragranular neurons in autism. However, further stereological analysis of the number of cells and cell volumes in specific cortical areas is needed to better establish the cellular phenotype of the autistic cerebral cortex and to understand its clinical relevance in autism.

Preliminary findings suggest the number and volume of supragranular and infragranular pyramidal neurons are similar in the anterior superior temporal area of control subjects and subjects with autism.

Jeanelle Ariza

Department of Pathology and Laboratory Medicine

University of California, Davis

Calibrated Forceps Model of Spinal Cord Compression Injury

Jeanelle Ariza

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Pathology and Laboratory Medicine

University of California, Davis

Calibrated Forceps Model of Spinal Cord Compression Injury

Department of Pathology and Laboratory Medicine