controlled-cervical-laceration-injury-in-mice

Controlled Cervical Laceration Injury in Mice

Use of genetically modified mice enhances our  understanding of molecular mechanisms underlying several neurological disorders  such as a spinal cord ...

a-novel-vertebral-stabilization-method-for-producing-contusive-spinal

A Novel Vertebral Stabilization Method for Producing  Contusive Spinal Cord Injury

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing ...

Indiana University School of Medicine

Secondary damage following primary spinal cord injury extends pathology beyond the site of initial trauma, and effective management is imperative for maximizing anatomical and functional recovery. Bisperoxovanadium compounds have proven neuroprotective effects in several central nervous system injury/disease models, however, no mechanism has been linked to such neuroprotection from bisperoxovanadium treatment following spinal trauma. The goal of this study was to assess acute bisperoxovanadium treatment effects on neuroprotection and functional recovery following cervical unilateral contusive spinal cord injury, and investigate a potential mechanism of the compound's action. Two experimental groups of rats were established to 1) assess twice-daily 7 day treatment of the compound, potassium bisperoxo (picolinato) vanadium, on long-term recovery of skilled forelimb activity using a novel food manipulation test, and neuroprotection 6 weeks following injury and 2) elucidate an acute mechanistic link for the action of the drug post-injury. Immunofluorescence and Western blotting were performed to assess cellular signaling 1 day following SCI, and histochemistry and forelimb functional analysis were utilized to assess neuroprotection and recovery 6 weeks after injury. Bisperoxovanadium promoted significant neuroprotection through reduced motorneuron death, increased tissue sparing, and minimized cavity formation in rats. Enhanced forelimb functional ability during a treat-eating assessment was also observed. Additionally, bisperoxovanadium significantly enhanced downstream Akt and mammalian target of rapamycin signaling and reduced autophagic activity, suggesting inhibition of the phosphatase and tensin homologue deleted on chromosome ten as a potential mechanism of bisperoxovanadium action following traumatic spinal cord injury. Overall, this study demonstrates the efficacy of a clinically applicable pharmacological therapy for rapid initiation of neuroprotection post-spinal cord injury, and sheds light on the signaling involved in its action.

Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury.

Des dommages secondaires apr&egrave;s l&eacute;sion m&eacute;dullaire primaire s&#39;&eacute;tend pathologie au-del&agrave; du site du traumatisme initial, et une gestion efficace est indispensable pour maximiser la r&eacute;cup&eacute;ration anatomique et fonctionnelle. Compos&eacute;s de Bisperoxovanadium ont d&eacute;montr&eacute; des effets neuroprotecteurs dans plusieurs mod&egrave;les de l&eacute;sion ou de maladie du syst&egrave;me nerveux central, toutefois, aucun m&eacute;canisme n&#39;a &eacute;t&eacute; li&eacute;e &agrave; ce neuroprotection de bisperoxovanadium traitement suite &agrave; un traumatisme spinal. L&#39;objectif de cette &eacute;tude &eacute;tait d&#39;&eacute;valuer les effets du traitement sur la neuroprotection et la r&eacute;cup&eacute;ration fonctionnelle apr&egrave;s l&eacute;sion cervicale unilat&eacute;ral contusion m&eacute;dullaire aigu&euml; bisperoxovanadium et d&#39;enqu&ecirc;ter sur un &eacute;ventuel m&eacute;canisme d&#39;action du compos&eacute;. Deux groupes de rats ont &eacute;t&eacute; &eacute;tablis pour 1) &eacute;valuer le traitement deux fois par jour 7 jour du vanadium compos&eacute;, de bisperoxo (picolinato) de potassium, sur un rel&egrave;vement &agrave; long terme d&#39;activit&eacute; qualifi&eacute;e membre ant&eacute;rieur en utilisant un test de manipulation des aliments nouveaux et neuroprotection 6 semaines apr&egrave;s une blessure et 2) &eacute;lucider un lien m&eacute;caniste aigu&euml; pour l&#39;action de l&#39;apr&egrave;s l&eacute;sion de drogue. Immunofluorescence et &eacute;ponger occidental ont &eacute;t&eacute; r&eacute;alis&eacute;s pour d&eacute;terminer cellulaire signalisation 1 jour suivant SCI et analyse fonctionnelle histochimie et les membres ant&eacute;rieurs ont &eacute;t&eacute; utilis&eacute;s pour &eacute;valuer la neuroprotection et la r&eacute;cup&eacute;ration 6 semaines apr&egrave;s une blessure. Bisperoxovanadium promu neuroprotection significative par la mort des motoneurones r&eacute;duite, a augment&eacute; l&#39;&eacute;pargnant les tissus et r&eacute;duit au minimum la formation de la cavit&eacute; chez les rats. On observa aussi am&eacute;lior&eacute;e des membres ant&eacute;rieurs de capacit&eacute; fonctionnelle pendant une &eacute;valuation de mangeurs de r&eacute;gal. En outre, bisperoxovanadium sensiblement am&eacute;lior&eacute;e en aval Akt et mammalian target of rapamycin signalisation et r&eacute;duit l&#39;activit&eacute; autophagique, sugg&eacute;rant l&#39;inhibition de la phosphatase et tensine homologue supprim&eacute; sur le chromosome 10 comme un m&eacute;canisme potentiel d&#39;action de bisperoxovanadium apr&egrave;s le traumatisme de la moelle &eacute;pini&egrave;re. Dans l&#39;ensemble, cette &eacute;tude d&eacute;montre l&#39;efficacit&eacute; d&#39;une th&eacute;rapie pharmacologique cliniquement applicable pour l&#39;ouverture rapide de neuroprotection post-spinal &eacute;pini&egrave;re et met en lumi&egrave;re la signalisation impliqu&eacute;s dans son action.

Bisperoxovanadium syst&eacute;mique active Akt/mTOR, r&eacute;duit l&#39;autophagie et am&eacute;liore la r&eacute;cup&eacute;ration apr&egrave;s une blessure de la moelle &eacute;pini&egrave;re cervicale.

Danni secondari dopo lesione primaria del midollo spinale si estende patologia oltre il sito di trauma iniziale, ed efficacia gestione &egrave; indispensabile per massimizzare il recupero anatomico e funzionale. Bisperoxovanadium composti hanno dimostrato effetti neuroprotettivi in diversi modelli di infortunio/malattia del sistema nervoso centrale, tuttavia, nessun meccanismo &egrave; stata collegata a tale neuroprotezione dal trattamento di bisperoxovanadium seguito di un trauma spinale. L&#39;obiettivo di questo studio era di valutare gli effetti del trattamento acuto bisperoxovanadium sulla neuroprotezione e recupero funzionale dopo lesione del midollo spinale cervicale Cantada unilaterale e indagare un potenziale meccanismo d&#39;azione del complesso. 1) Valutare due volte al giorno 7 giorni di trattamento del composto, vanadio bisperoxo (picolinato) di potassio, il recupero a lungo termine dell&#39;attivit&agrave; degli arti anteriori qualificati utilizzando un test di manipolazione alimentare e neuroprotezione 6 settimane a seguito di infortunio e 2) delucidare un collegamento meccanicistico acuto per l&#39;azione della post-injury della droga sono stati stabiliti due gruppi sperimentali di ratti. Immunofluorescenza e macchiarsi occidentale sono stati eseguiti per valutare cellular signaling 1 giorno dopo SCI e analisi funzionale istochimica e degli arti anteriori erano utilizzate per valutare la neuroprotezione e recupero 6 settimane dopo l&#39;infortunio. Bisperoxovanadium promosso neuroprotezione significativo attraverso la morte motorneuron ridotta, aumentata tissue sparing e ridotto al minimo la formazione di cavit&agrave; nei ratti. &Egrave; stato osservato anche l&#39;arto rafforzata capacit&agrave; funzionale durante una valutazione di trattare-mangiare. Inoltre, bisperoxovanadium significativamente migliorato a valle Akt e mammiferi bersaglio della rapamicina segnalazione e ridotta attivit&agrave; autophagic, suggerendo inibizione della fosfatasi e Tensina omologo eliminato sul cromosoma dieci come un potenziale meccanismo d&#39;azione di bisperoxovanadium seguito di lesioni traumatiche del midollo spinale. Nel complesso, questo studio dimostra l&#39;efficacia di una terapia farmacologica clinicamente applicabile per l&#39;avvio rapido di neuroprotezione post-spinal cord injury e getta luce sulla segnalazione coinvolti nella sua azione.

Bisperoxovanadium sistemica attiva Akt/mTOR, riduce autophagy e migliora il recupero dopo lesioni del midollo spinale cervicale.

Reliable animal models of traumatic brain injury (TBI) are essential to test novel hypotheses and therapeutic interventions. In this study, based on advantages of both the closed head injury (CHI) and controlled cortical impact (CCI) models, we developed a bilateral head injury model in mice. C57BL/6 mice were used in this study. A midline craniotomy (5mm diameter) was performed extending 2mm anteriorly and 3mm posteriorly from the bregma, centered over the sagittal suture. The skull flap was left in place. A cortical impact on the surface of the skull flap was performed using an electromagnetic impactor. Here we report that the injury significantly decreased the neuroscore and increased foot drops in a severity-dependent manner. Severity-related deficits in performance on a rotarod device were also found at both slow and fast accelerations. These findings suggest that our TBI model can produce graded motor deficits. In addition, Morris water maze testing showed increased latency to locate a hidden platform in a severity-dependent manner, suggesting that our model can also produce graded memory deficits. Furthermore, an adhesive removal test revealed significant increases in time-to-contact and time-to-remove the adhesive tape from the paw in a severity-dependent manner, indicating that our TBI model produced graded somatosensory and motor deficits. Histological analysis presented a clear gradation in brain tissue damage following graded brain injuries. These findings collectively suggest that the current model may offer a sensitive, reliable and clinically-relevant model for assessments of therapeutic strategies forTBI.

A bilateral head injury that shows graded brain damage and behavioral deficits in adultmice.

Des mod&egrave;les animaux fiables de traumatisme cr&acirc;nien (TCC) sont essentielles pour tester de nouvelles hypoth&egrave;ses et des interventions th&eacute;rapeutiques. Dans cette &eacute;tude, bas&eacute;e sur les avantages de ces deux le traumatisme cr&acirc;nien ferm&eacute; (CHI) et contr&ocirc;l&eacute;e des mod&egrave;les d&#39;impact corticale (CCI), nous avons d&eacute;velopp&eacute; un mod&egrave;le bilat&eacute;ral de traumatismes cr&acirc;niens chez les souris. Souris C57BL/6 ont &eacute;t&eacute; utilis&eacute;es dans cette &eacute;tude. Une craniotomie de la ligne m&eacute;diane (5mm de diam&egrave;tre) a &eacute;t&eacute; r&eacute;alis&eacute;e en allant 2mm vers l&#39;avant et 3mm vers l&#39;arri&egrave;re du bregma, centr&eacute;e autour de la suture sagittale. Le rabat du cr&acirc;ne a &eacute;t&eacute; laiss&eacute; en place. Un impact cortical sur la surface de la poitrine du cr&acirc;ne a &eacute;t&eacute; r&eacute;alis&eacute; &agrave; l&#39;aide d&#39;un impacteur &eacute;lectromagn&eacute;tique. Nous rapportons ici que la blessure significativement diminu&eacute; la neuroscore et a augment&eacute; de gouttes de pied en fonction de la gravit&eacute;. Ax&eacute;s sur la gravit&eacute; des d&eacute;ficits en performances sur un dispositif rotarod se retrouvent &eacute;galement &agrave; des acc&eacute;l&eacute;rations lentes et rapides. Ces r&eacute;sultats donnent &agrave; penser que notre mod&egrave;le TBI peut produire des d&eacute;ficits moteurs gradu&eacute;es. En outre, Morris eau labyrinthe tests ont montr&eacute; une latence accrue pour localiser une plate-forme cach&eacute;e dans une fa&ccedil;on d&eacute;pendante de gravit&eacute;, ce qui sugg&egrave;re que notre mod&egrave;le peut &eacute;galement produire des d&eacute;ficits de m&eacute;moire gradu&eacute;es. De plus, un test de suppression adh&eacute;sif a r&eacute;v&eacute;l&eacute; des augmentations significatives dans le temps-&agrave;-contact et de temps &agrave; enlever le ruban adh&eacute;sif de la patte d&#39;une mani&egrave;re d&eacute;pendante de s&eacute;v&eacute;rit&eacute;, indiquant que notre mod&egrave;le TBI produit class&eacute; des d&eacute;ficits moteurs et somatosensoriels. L&#39;analyse histologique a pr&eacute;sent&eacute; un cerveau de gradation claire en dommages de tissu de cerveau suivant class&eacute; blessures. Collectivement, ces r&eacute;sultats sugg&egrave;rent que le mod&egrave;le actuel peut offrir un mod&egrave;le sensible, fiable et ayant une pertinence clinique pour l&#39;&eacute;valuation des strat&eacute;gies th&eacute;rapeutiques forTBI.

Un traumatisme cr&acirc;nien bilat&eacute;raux qui montre gradu&eacute;e des l&eacute;sions c&eacute;r&eacute;brales et des d&eacute;ficits comportementaux dans adultmice.

Modelli animali affidabile di lesioni cerebrali traumatiche (TBI) sono essenziali per testare nuove ipotesi e gli interventi terapeutici. In questo studio, basato sui vantaggi di entrambe le chiusa cranico (CHI) e controllato modelli corticali impatto (CCI), abbiamo sviluppato un modello di trauma cranico bilaterale nei topi. In questo studio sono stati utilizzati topi C57BL/6. Una craniotomia della linea mediana (5mm di diametro) &egrave; stata eseguita estendendo 2mm anteriormente e 3mm posteriormente dal bregma, centrato sopra la sutura sagittale. Il lembo del cranio &egrave; stato lasciato sul posto. Un impatto corticale sulla superficie del lembo cranio &egrave; stato eseguito utilizzando un dispositivo di simulazione elettromagnetica. Qui riportiamo che il pregiudizio significativamente diminuito il neuroscore e gocce di piede &egrave; aumentato in maniera dipendente dalla gravit&agrave;. Correlati a gravit&agrave; deficit di prestazioni in un dispositivo rotarod furono trovati anche a accelerazioni sia lente e veloce. Questi risultati suggeriscono che il nostro modello TBI pu&ograve; produrre deficit motori graduata. Inoltre, Morris water maze test ha mostrato maggiore latenza per individuare una piattaforma nascosta in maniera dipendente dalla gravit&agrave;, suggerendo che il nostro modello pu&ograve; produrre anche deficit di memoria graduata. Inoltre, un test di rimozione adesivo rivelato significativo che aumenta nel tempo di contatto e tempo per rimuovere il nastro adesivo dalla zampa in maniera dipendente dalla gravit&agrave;, che indica che il nostro modello TBI prodotto classificato deficit somatosensoriali e motori. L&#39;analisi istologica ha presentato un cervello di chiara gradazione in danno di tessuto cerebrale seguito classificato lesioni. Collettivamente, questi risultati suggeriscono che l&#39;attuale modello pu&ograve; offrire un modello sensibile, affidabile e clinicamente rilevante per la valutazione di strategie terapeutiche forTBI.

ArticleTotal : 2	Year
Publication title Cited by 16	2013
Publication title Cited by 20	2015

Article	Year
Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury. PloS one\| PubMed ID: 22253859	2012
A bilateral head injury that shows graded brain damage and behavioral deficits in adultmice. Brain research\| PubMed ID: 23276498	2013

Chandler L. Walker

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