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 ...

spinal-cord-lateral-hemisection-asymmetric-behavioral-assessments

Spinal Cord Lateral Hemisection and Asymmetric Behavioral Assessments in Adult Rats

Incomplete spinal cord injury (SCI) often leads to impairments of sensorimotor functions and is clinically the most frequent type of SCI. Human ...

Indiana University School of Medicine

Individuals learn associations between alcohol's sensory properties and intoxication, with such conditioned stimuli (CS) becoming involved in craving and relapse. However, these CS also carry idiosyncratic associations.

fMRI of the brain's response to stimuli experimentally paired with alcohol intoxication.

Les individus apprennent les associations entre les propri&eacute;t&eacute;s sensorielles de l&#39;alcool et l&#39;intoxication, avec ces stimulus conditionn&eacute; (CS) s&#39;engager dans la soif et de rechute. Cependant, ces CS portent &eacute;galement des associations idiosyncrasiques.

IRMf de la r&eacute;ponse du cerveau &agrave; un stimulus associ&eacute; exp&eacute;rimentalement &agrave; une intoxication alcoolique.

Individui imparano le associazioni tra propriet&agrave; sensoriali di alcool e intossicazione, con tali stimoli condizionati (CS) diventando coinvolte nel desiderio e ricaduta. Tuttavia, queste CS portare anche associazioni idiosincratiche.

fMRI di risposta del cervello agli stimoli sperimentalmente accoppiato con intossicazione da alcol.

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.

Spinal cord injury (SCI) is devastating, causing sensorimotor impairments and paralysis. Persisting functional limitations on physical activity negatively affect overall health in individuals with SCI. Physical training may improve motor function by affecting cellular and molecular responses of motor pathways in the central nervous system (CNS) after SCI. Although motoneurons form the final common path for motor output from the CNS, little is known concerning the effect of exercise training on spared motoneurons below the level of injury. Here we examined the effect of treadmill training on morphological, trophic, and synaptic changes in the lumbar motoneuron pool and on behavior recovery after a moderate contusive SCI inflicted at the 9th thoracic vertebral level (T9) using an Infinite Horizon (IH, 200 kDyne) impactor. We found that treadmill training significantly improved locomotor function, assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale, and reduced foot drops, assessed by grid walking performance, as compared with non-training. Additionally, treadmill training significantly increased the total neurite length per lumbar motoneuron innervating the soleus and tibialis anterior muscles of the hindlimbs as compared to non-training. Moreover, treadmill training significantly increased the expression of a neurotrophin brain-derived neurotrophic factor (BDNF) in the lumbar motoneurons as compared to non-training. Finally, treadmill training significantly increased synaptic density, identified by synaptophysin immunoreactivity, in the lumbar motoneuron pool as compared to non-training. However, the density of serotonergic terminals in the same regions did not show a significant difference between treadmill training and non-training. Thus, our study provides a biological basis for exercise training as an effective medical practice to improve recovery after SCI. Such an effect may be mediated by synaptic plasticity, and neurotrophic modification in the spared lumbar motoneuron pool caudal to a thoracic contusive SCI.

Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury.

Cervical injuries are the most common form of spinal cord injury (SCI), and are often complicated by pathological secondary damage. Therefore, cervical SCI is of great clinical importance for understanding pathology and potential therapies. Here we utilize a weight drop cervical hemi-contusion injury model using a NYU/MASCIS impactor that produced graded anatomical and functional deficits.

Anatomical and functional effects of lateral cervical hemicontusion in adult rats.

Following an initial mechanical insult, traumatic spinal cord injury (SCI) induces a secondary wave of injury, resulting in a toxic lesion environment inhibitory to axonal regeneration. This review focuses on the glial cell line-derived neurotrophic factor (GDNF) and its application, in combination with other factors and cell transplantations, for repairing the injured spinal cord. As studies of recent decades strongly suggest that combinational treatment approaches hold the greatest therapeutic potential for the central nervous system (CNS) trauma, future directions of combinational therapies will also be discussed.

History of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Its Use for Spinal Cord Injury Repair.

Spinal cord injury (SCI) afflicts hundreds of thousands of Americans, and most SCI (~80%) occurs in males. In experimental animal models, however, many studies used females. Funding agencies like the National Institutes of Health recommend that new proposed studies should include both genders due to variations in gender response to injuries, diseases, and treatments. However, cost and considerations for some animal models, such as SCI, affect investigators in adapting to this recommendation. Research has increased comparing gender effects in various disease and injury models, including SCI. However, most studies use weight-matched animals which poses issues in comparing results and outcomes. The present study compared histologic and functional outcomes between age-matched male and female Sprague-Dawley rats in a moderate thoracic contusion SCI model. Cresyl-violet and eosin staining showed no significant differences in lesion volume between genders after nine weeks post-SCI (P>0.05). Luxol fast blue stained spared myelin was similar between genders, though slightly greater (~6%) in spared myelin compared to cord volume (P=0.044). Glial reactivity and macrophage labeling in the lesion area was comparable between genders, as well. Basso, Beattie, Bresnahan (BBB) functional scores were not significantly different between genders, and Hargreaves thermal hyperalgesia and Gridwalk sensorimotor analyses were also similar between genders compared to uninjured gender controls. Analysis of covariance (ANCOVA) showed weight did not influence functional recovery as assessed through BBB (P=0.65) or Gridwalk assessment (P=0.63) in this study. In conclusion, our findings suggest age-matched male and female rats recover similarly in a common clinically-relevant SCI model.

ArticleTotal : 3	Year
Publication title Cited by 16	2013
Publication title Cited by 20	2015
Publication title Cited by 20	2020

Article	Year
fMRI of the brain's response to stimuli experimentally paired with alcohol intoxication. Psychopharmacology\| PubMed ID: 21993878	2012
Systemic bisperoxovanadium activates Akt/mTOR, reduces autophagy, and enhances recovery following cervical spinal cord injury. PloS one\| PubMed ID: 22253859	2012
Treadmill training induced lumbar motoneuron dendritic plasticity and behavior recovery in adult rats after a thoracic contusive spinal cord injury. Experimental neurology\| PubMed ID: 26164199	2015
Anatomical and functional effects of lateral cervical hemicontusion in adult rats. Restorative neurology and neuroscience\| PubMed ID: 27163248	2016
History of Glial Cell Line-Derived Neurotrophic Factor (GDNF) and Its Use for Spinal Cord Injury Repair. Brain sciences\| PubMed ID: 29899247	2018
Functional and histological gender comparison of age-matched rats after moderate thoracic contusive spinal cord injury. Journal of neurotrauma\| PubMed ID: 30489213	2018

Melissa J. Walker

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