Este trabalho foi apoiado pelo financiamento do Cordão Indiana Spinal &amp; Brain Injury Research Grants (SCBI 200-12), o Ralph W. and Grace M. Showalter Research Award, da Universidade de Indiana Biological Research Grant, NIH concede RR025761 e 1R21NS072631-01A.

Animal Care Masculino C57 BL / 6 machos foram alojados em grupo e mantidos em um ciclo claro / escuro 12/12 horas de luz com acesso ao acesso a alimentos e água ad libitum. Os animais utilizados neste protocolo foram 10-12 semanas de idade. Todos os procedimentos foram realizados sob protocolos aprovados pelo Comitê Animal Care e Use da Universidade de Indiana. 1. Preparação Cirúrgica <ol><li> Anestesiar o rato usando uma mistura de cetamina / xilazina (87,7 mg / ml de cetamina e 12,3 mg / ml de xilazina) e administrar (1 ml / kg), por injecção IP. </li><li> Raspar a cabeça do rato entre as orelhas. </li><li> Aplique uma geléia à base de petróleo para os olhos do mouse para evitar ressecamento durante a cirurgia. </li><li> Limpe a área de barba feita com 10% de iodo. Em seguida, use álcool 70% para limpar o iodo. </li><li> Fixe a cabeça do rato na moldura estereotáxica usando as barras de ouvido e placa de mordida. Certifique-se de que o cérebro é estável. </li></ol> 2. Craniectomia </p&gt; <ol><li> Fazer uma incisão longitudinal no meio da cabeça com uma tesoura. Use uma pinça hemostática para manter a pele para o lado esquerdo. </li><li> Usar um aplicador com ponta de algodão para remover o sangue e o tecido no osso para expor o crânio. Permitir crânio exposto a secar durante 1 min. </li><li> Use uma pinça para aplicar a pressão e garantir que o crânio permanece imóvel. Identificar pontos anatômicos Lambda (aspecto caudal) e Bregma (aspecto frontal). Desenhar um circulo no centro da Lambda e Bregma com um diâmetro de 4 mm e 0,5 mm da linha média. </li><li> Use uma broca para cortar ao longo do círculo marcado. Suavemente soprar pó de osso de distância. Não perfure completamente através do osso para evitar danificar a dura-máter. </li><li> Use uma pinça para remover o osso e expor a dura-máter. </li></ol> 3. Impactação O sistema de impacto inclui uma caixa de controle para definir os parâmetros de impacto, um atuador para realizar a compactação, e um quadro estereotáxico para garantir o atouator e cabeça de rato para o impacto. <ol><li> Pré-estabelecidos da velocidade do actuador de 3 m / s antes da cirurgia. </li><li> Pré-definido diferente profundidade deformação para induzir diferentes gravidades da lesão. Profundezas de Deformação de 0,0-0,2 mm, 0,5-1,0 mm e 1,2-2,0 mm resultaria em Tbis leve, moderada e grave, respectivamente. Este protocolo explicado como conseguir uma lesão cerebral moderadamente grave, com uma profundidade de deformação de um milímetro por meio de uma velocidade de 3 m / seg. </li><li> Fixe o atuador para o titular na armação estereotáxica e usar os micromanipuladores movê-lo para garantir a ponta redonda e plana do atuador (3 mm de diâmetro) no centro da área do crânio aberto. Em seguida, ajustar a ponta em ângulo paralelo à superfície do local do impacto. </li><li> Estabelecer o ponto zero, movendo-se o atuador no modelo que prorroga até a ponta toca a superfície do local do impacto. Em seguida, defina o canal Z no painel de controle estereotáxico para zero. </li><li> Recolha a ponta pênduloenquanto se move para baixo, simultaneamente, o actuador de um milímetro. </li><li> Aperte o botão de impacto para atingir o local da lesão e atingir uma profundidade de deformação de 1 mm. </li></ol> 4. Lesão site Encerramento <ol><li> Utilize aplicadores com ponta de algodão para remover qualquer impacto sangue seguinte, mas não toque na área da lesão. </li><li> Coloque o mouse sobre uma almofada quente para manter a temperatura corporal. </li><li> Uma vez que o sangramento parou, suturar a ferida fechada. Coloque o animal de volta para a gaiola limpa e permitir que ele se recuperar da cirurgia durante a noite na almofada quente. </li><li> Administrar Buprenorfina 0,05-0,10 mg / kg SQ cada 8-12 horas por 2 dias após a cirurgia. </li></ol>

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The authors have nothing to disclose.

Os passos mais críticos para a geração de sucesso Tbis consistentes usando um sistema impacto ímã eletrônico para causar um CCI são: 1) de forma estável a fixação da cabeça do rato na moldura estereotáxica; 2) gerar o mesmo tamanho da janela de osso entre ratinhos e remoção do osso, sem danificar a dura por baixo durante a craniotomia; 3) posicionar corretamente a ponta impacto no centro da área aberta e estabelecer o ponto zero antes de colidir. A cabeça de rato deve ser fix...

Traumatismo crânio-encefálico (TCE) é definido como uma alteração no funcionamento do cérebro, ou outra evidência de patologia cerebral, causada por uma força externa 1. Tbis continuam a ser um grave problema de saúde em todo o mundo, especialmente nos Estados Unidos. De acordo com os Centros de Controle e Prevenção de Doenças, pelo menos 1,7 milhão de Tbis ocorrem anualmente nos Estados Unidos, resultando em 30,5% de todas as mortes relacionadas com a lesão. Em 2000, os custos médicos diretos e custos indiretos de Tbis totalizaram um valor estimado de 76.500 milhões dólares nos Estados Unidos sozinho. Embora os avanços tecnológicos e terapêuticos em décadas anteriores melhoraram a qualidade ea duração da vida para aqueles que sofrem de Tbis, nenhuma farmacêutica eficaz ou tratamentos preventivos existem atualmente. Devido à complexidade e os efeitos de grande alcance de Tbis, incluindo lesões teciduais, morte celular e degeneração de axônios, não há duas lesões são idênticas; assim, nenhum modelo de TBI atual para animais reproduz com precisãotodos os aspectos do TCE, como visto nos seres humanos. No entanto, os modelos animais não fornecem a capacidade para produzir lesões quase idênticos necessários para investigar os efeitos de vários TCE com a esperança de compreender ainda as manifestações clínicas da lesão cerebral traumática. O modelo de impacto cortical controlado (CCI) utiliza um sistema de impacto para gerar impacto físico para a dura-máter de um animal exposto. Induz Tbis que variam de leve a grave semelhantes às vividas por seres humanos. Esta lesão foi caracterizado pela primeira vez no furão, 2 e depois foi adaptada para uso no rato 3,4, rato 5-7, e ovelhas 8. Desde a primeira caracterização, o local da lesão foi colocada tanto sobre a linha média e 2,9 a cortical lateral 10. CCI fornece um método fácil e preciso de investigar os efeitos e tratamentos potenciais para Tbis. Além do modelo de CCI, a percussão do fluido e da queda de peso modelos são commonly usado para produzir Tbis. No entanto, estes modelos apresentam limitações, incluindo menos controle sobre parâmetros de lesão, produzindo alterações histopathalogical não vistos em Tbis humano e uma maior incidência de morte acidental em ratos 3,5,10. O modelo de onda de choque também é usado para produzir Tbis. Embora o modelo de onda de choque não reproduz as mudanças histopathalogical visto após um impacto mecânico, este modelo não produz precisão Tbis experientes particularmente por militares 11. O modelo de impacto cortical controlado é fácil de controlar, devido ao controlo preciso sobre os parâmetros de deformação, tais como tempo, velocidade e profundidade de impacto 5. Essa precisão torna replicando lesões quase idênticas em todo um grupo inteiro de animais mais viáveis. Mais importante ainda, CCI reproduz Tbis com características vistas em Tbis humano 12. No entanto, não existe um modelo único animal que é totalmente bem-sucedido em reproduzir o espectro completo de patológico changes observadas após o TCE. Mais pesquisas são necessárias para revelar plenamente as alterações agudas e crônicas que ocorrem após o TCE. Dois tipos de lesões ocorrem após um TCE: lesões primárias e secundárias. A lesão primária ocorre no momento do impacto, e não é sensível a tratamentos terapêuticos; No entanto, as lesões secundárias que persistem após a lesão inicial, estão sujeitos a tratamentos de 13. O modelo de impacto cortical controlado produz a lesão primária, permitindo assim que os pesquisadores a investigar os efeitos da TBI e potenciais tratamentos terapêuticos para os efeitos potencialmente duradouros de lesões secundárias. Áreas de pesquisa potencial utilizando o modelo de CCI incluem morte neuronal, edema cerebral, a neurogênese, efeitos vasculares, alterações histopathalogical e déficits de memória e mais 3,13-16.

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controlled cortical impact model for traumatic brain injury

Every year over a million Americans suffer a traumatic brain injury (TBI). Combined with the incidence of TBIs worldwide, the physical, emotional, social, and economical effects are staggering. Therefore, further research into the effects of TBI and effective treatments is necessary. The controlled cortical impact (CCI) model induces traumatic brain injuries ranging from mild to severe. This method uses a rigid impactor to deliver mechanical energy to an intact dura exposed following a craniectomy. Impact is made under precise parameters at a set velocity to achieve a pre-determined deformation depth. Although other TBI models, such as weight drop and fluid percussion, exist, CCI is more accurate, easier to control, and most importantly, produces traumatic brain injuries similar to those seen in humans. However, no TBI model is currently able to reproduce pathological changes identical to those seen in human patients. The CCI model allows investigation into the short-term and long-term effects of TBI, such as neuronal death, memory deficits, and cerebral edema, as well as potential therapeutic treatments for TBI.

O modelo de impacto cortical controlado produz Tbis que variam em gravidade de leve a grave. Pós-impacto a quantidade de inchaço craniano, hemorragia e distorção cranial no local do impacto irá revelar a gravidade da lesão resultante dos parâmetros de velocidade e profundidade deformação. Tbis leves resultar em inchaço craniano no local do impacto e um leve sangramento, devido à quebra dura limitado. A TCE moderado apresenta inchaço craniano e aumento de sangramento devido à quebra dura em cima de impactaç...

Watch this Scientific Journal Video about Controlled Cortical Impact Model for Traumatic Brain Injury at JoVE.com

Controlled Cortical Impact Model for Traumatic Brain Injury

Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Controlado Modelo Impact Cortical para lesão cerebral traumática

Every year over a million Americans suffer a traumatic brain injury (TBI).  Combined with the incidence of TBIs worldwide, the physical, emotional, ...

controlled-cortical-impact-model-for-traumatic-brain-injury

Research

JoVE Journal

Medicine

28.4K visualizações.  Indiana University School of Medicine. Traumatic brain injuries (TBIs) remain a serious health problem. Using the controlled cortical impact surgery model, research on the effects of TBI and possible treatment methods may be performed.

Vídeo: Controlled Cortical Impact Model for Traumatic Brain Injury

Pressure Controlled Ventilation to Induce Acute Lung Injury in Mice

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged mechanical ventilation, contributes to morbidity and mortality of critical illness, and studies on novel genetic or pharmacological targets are areas of intense investigation (1-3, 5, 8, 26, 30, 33-36). ALI is defined by the acute onset of the disease, which leads to non-cardiac pulmonary edema and subsequent impairment of pulmonary gas exchange (36). We have developed a murine model of ALI by using a pressure-controlled ventilation to induce ventilator-induced lung injury (2). For this purpose, C57BL/6 mice are anesthetized and a tracheotomy is performed followed by induction of ALI via mechanical ventilation. Mice are ventilated in a pressure-controlled setting with an inspiratory peak pressure of 45 mbar over 1 - 3 hours. As outcome parameters, pulmonary edema (wet-to-dry ratio), bronchoalveolar fluid albumin content, bronchoalveolar fluid and pulmonary tissue myeloperoxidase content and pulmonary gas exchange are assessed (2). Using this technique we could show that it sufficiently induces acute lung inflammation and can distinguish between different treatment groups or genotypes (1-3, 5). Therefore this technique may be helpful for researchers who pursue molecular mechanisms involved in ALI using a genetic approach in mice with gene-targeted deletion.

A murine model for ventilator induced lung injury is an important tool to study an acute lung injury in vivo. Here, we report an easy applicable in situ model for acute lung injury using high-pressure mechanical ventilation to induce acute failure of the lung.

Ventilação a pressão controlada para induzir lesão pulmonar aguda em ratos

Murine models are extensively used to investigate acute injuries of different organs systems (1-34). Acute lung injury (ALI), which occurs with prolonged ...

Medicina

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 injury (SCI). Freehand manual control used to produce a laceration model of SCI creates inconsistent injuries often associated with a crush or contusion component and, therefore, a novel technique was developed. Our model of cervical laceration SCI has resolved inherent difficulties with the freehand method by incorporating 1) cervical vertebral stabilization by vertebral facet fixation, 2) enhanced spinal cord exposure, and 3) creation of a reproducible laceration of the spinal cord using an oscillating blade with an accuracy of &plusmn;0.01 mm in depth without associated contusion. Compared to the standard methods of creating a SCI laceration such as freehand use of a scalpel or scissors, our method has produced a consistent lesion. This method is useful for studies on axonal regeneration of corticospinal, rubrospinal, and dorsal ascending tracts.

A novel technique to create a reproducible in vivo model of cervical spinal cord laceration injury in the mouse is described. This technique is based on spine stabilization by fixation of the cervical facets and laceration of the spinal cord using an oscillating blade with an accuracy of &plusmn;0.01 mm.

Controlada por laceração do colo do útero em camundongos

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

Stretch in Brain Microvascular Endothelial Cells (cEND) as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying mechanisms involved in it are useful for treatment. There are both in vivo and in vitro methods available for this purpose. In vivo models can mimic actual head injury as it occurs during TBI. However, in vivo techniques may not be exploited for studies at the cell physiology level. Hence, in vitro methods are more advantageous for this purpose since they provide easier access to the cells and the extracellular environment for manipulation.
Our protocol presents an in vitro model of TBI using stretch injury in brain microvascular endothelial cells. It utilizes pressure applied to the cells cultured in flexible-bottomed wells. The pressure applied may easily be controlled and can produce injury that ranges from low to severe. The murine brain microvascular endothelial cells (cEND) generated in our laboratory is a well-suited model for the blood brain barrier (BBB) thus providing an advantage to other systems that employ a similar technique. In addition, due to the simplicity of the method, experimental set-ups are easily duplicated. Thus, this model can be used in studying the cellular and molecular mechanisms involved in TBI at the BBB.

Stretch in Brain Microvascular Endothelial Cells cEND as an In Vitro Traumatic Brain Injury Model of the Blood Brain Barrier

In vitro traumatic brain injury models are being developed to reproduce in vivo brain deformation. Stretch-induced injury has been employed for astrocytes, neurons, glial cells, aortic, and brain endothelial cells. However, our system uses a blood brain barrier (BBB) model that possesses properties constituting a legitimate model of the BBB to establish an in vitro&#160;TBI model.

Estique em células cerebrais endoteliais microvasculares (cEnd) como um<em&gt; In Vitro</em&gt; Modelo de lesão cerebral traumática do cérebro Barreira Hemato

Due to the high mortality incident brought about by traumatic brain injury (TBI), methods that would enable one to better understand the underlying ...

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable during renal transplantation. Experimental models that accurately and reproducibly recapitulate renal IRI are crucial in dissecting the pathophysiology of AKI and the development of novel therapeutic agents. Presented here is a mouse model of renal IRI that results in reproducible AKI. This is achieved by a midline laparotomy approach for the surgery with one incision allowing both a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia of the left kidney. By careful monitoring of the clamp position and body temperature during the period of ischaemia this model achieves reproducible functional and structural injury. Mice sacrificed 24 hr&#160;following surgery demonstrate loss of renal function with elevation of the serum or plasma creatinine level as well as structural kidney damage with acute tubular necrosis evident. Renal function improves and the acute tissue injury resolves during the course of 7 days following renal IRI such that this model may be used to study renal regeneration. This model of renal IRI has been utilized to study the molecular and cellular pathophysiology of AKI as well as analysis of the subsequent renal regeneration.

The mouse model of renal ischaemia reperfusion injury described here comprises of a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia that results in acute kidney injury. This model uses a midline laparotomy approach with all steps performed via one incision.

Renal Isquemia Reperfusão: um modelo do rato de lesão e regeneração

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable ...

A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls, a reliable animal model of mTBI had previously not been developed for this important aspect of development. The modified weight-drop technique employs a glancing impact to the head of a freely moving rodent transmitting acceleration, deceleration, and rotational forces upon the brain. When applied to juvenile rats, this modified weight-drop technique induced clinically relevant behavioural outcomes that were representative of post-concussion symptomology. The technique is a rapidly applied procedure with an extremely low mortality rate, rendering it ideal for high-throughput studies of therapeutics. In addition, because the procedure involves a mild injury to a closed head, it can easily be used for studies of repetitive brain injury. Owing to the simplistic nature of this technique, and the clinically relevant biomechanics of the injury pathophysiology, the modified weight-drop technique provides researchers with a reliable model of mTBI that can be used in a wide variety of behavioural, molecular, and genetic studies.

The modified weight-drop technique is an easy, cost-effective procedure used for the induction of mild traumatic brain injury in juvenile rats. This novel technique produces clinically relevant symptomology that will advance the study of mild traumatic brain injury (mTBI) and concussion.

Um novo modelo de Mild Traumatic Brain Injury para ratos jovens

Despite growing evidence that childhood represents a major risk period for mild traumatic brain injury (mTBI) from sports-related concussions, motor ...

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 calibrated forceps model of compression injury is a convenient, low cost, and very reproducible animal model for SCI. We used a pair of modified forceps in accordance with the method published by Plemel et al. (2008) to laterally compress the spinal cord to a distance of 0.35 mm. In this video, we will demonstrate a dorsal laminectomy to expose the spinal cord, followed by compression of the spinal cord with the modified forceps. In the video, we will also address issues related to the care of paraplegic laboratory animals. This injury model produces mice that exhibit impairment in sensation, as well as impaired hindlimb locomotor function. Furthermore, this method of injury produces consistent aberrations in the pathology of the SCI, as determined by immunohistochemical methods. After watching this video, viewers should be able to determine the necessary supplies and methods for producing SCI of various severities in the mouse for studies on SCI and/or treatments designed to mitigate impairment after injury.

Spinal cord injury models should be highly reproducible. We demonstrate that the calibrated forceps compression model of spinal cord injury is an easy to use surgical method for generating reproducible injuries to the murine spinal cord.

Calibrado Fórceps Modelo de Lesão Medular Compression

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

A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.

We introduce a tissue displacement-based contusive spinal cord injury model that can produce a consistent contusive spinal cord injury in adult mice.

Um Modelo de Lesão Medular Contusiva Baseado em Cilindrada de Tecidos em Ratos

Producing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between ...

A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal neurological deficits and even amnesia. Athletes participating in contact sports are at high risk of exposure to large number of mTBIs. In terms of the level of injury in a sporting athlete, a mTBI is defined as a mild injury that does not cause gross pathological changes, but does cause short-term neurological deficits that are spontaneously resolved. Despite previous attempts to model mTBI in mice and rats, many have reported gross adverse effects including skull fractures, intracerebral bleeding, axonal injury and neuronal cell death. Herein, we describe our highly reproducible animal model of mTBI that reproduces clinically relevant symptoms. This model uses a custom made pneumatic impactor device to deliver a closed-head trauma. This impact is made under precise velocity and deformation parameters, creating a reliable and reproducible model to examine the mechanisms that contribute to effects of single or repetitive concussive mTBI.

Athletes absorb several hundred mild traumatic brain injuries (mTBI)/concussions every year; however, the consequence of these on the brain is poorly understood. Therefore, an animal model of single and repetitive mTBI that consistently replicates clinically relevant symptoms provides the means to advance the study of mTBI and concussion.

Um modelo de mouse de lesões cerebrais traumáticas leves simples e repetitivas

Mild Traumatic Brain Injury (mTBI) can result in the acute loss of brain function, including a period of confusion, a loss of consciousness (LOC), focal ...

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of disorders of consciousness, disrupted higher brain function, and verbal disturbances. As a consequence of an insufficient ability to communicate, objective evaluations are needed from family members, medical staff, and caregivers. One such evaluation is the assessment of functioning brain areas. Recently, multimodal brain imaging has been used to explore the function of damaged brain areas. [18F]-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) is a successful tool for examining brain function. However, the assessment of brain glucose metabolism based on [18F]FDG-PET/CT is not standardized and depends on several varying parameters, as well as the patient&#39;s condition. Here, we describe a series of semiquantitative assessment protocols for a region-of-interest (ROI) image analysis using self-produced [18F]FDG tracers in patients with sTBI. The protocol focuses on screening the participants, preparing the [18F]FDG tracer in the hot lab, scheduling the acquisition of [18F]FDG-PET/CT brain images, and measuring glucose metabolism using the ROI analysis from a targeted brain area.

Semi-quantitative Assessment Using [18F]FDG Tracer in Patients with Severe Brain Injury

[18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography is useful for studying glucose metabolism related to brain function. Here, we present a protocol for an [18F]FDG tracer set-up and semiquantitative assessment of the region-of-interest analysis for targeted brain areas associated with clinical manifestations in patients with severe traumatic brain injury.

Avaliação semi-quantitativa usando [18F] FDG Tracer em pacientes com lesão cerebral grave

Patients with severe traumatic brain injury (sTBI) have difficulty knowing whether they are accurately expressing their thoughts and emotions because of ...

Tracking Superparamagnetic Iron Oxide-labeled Mesenchymal Stem Cells using MRI after Intranasal Delivery in a Traumatic Brain Injury Murine Model

Stem cell-based therapies for brain injuries, such as traumatic brain injury (TBI), are a promising approach for clinical trials. However, technical hurdles such as invasive cell delivery and tracking with low transplantation efficiency remain challenges in translational stem-based therapy. This article describes an emerging technique for stem cell labeling and tracking based on the labeling of the mesenchymal stem cells (MSCs) with superparamagnetic iron oxide (SPIO)&#160;nanoparticles, as well as intranasal delivery of the labeled MSCs. These nanoparticles are fluorescein isothiocyanate (FITC)-embedded and safe to label the MSCs, which are subsequently delivered to the brains of TBI-induced mice by the intranasal route. They are then tracked non-invasively in vivo by real-time magnetic resonance imaging (MRI). Important advantages of this technique that combines SPIO for cell labeling and intranasal delivery include (1) non-invasive, in vivo MSC tracking after delivery for long tracking periods, (2) the possibility of multiple dosing regimens due to the non-invasive route of MSC delivery, and (3) possible applications to humans, owing to the safety of SPIO, non-invasive nature of the cell-tracking method by MRI, and route of administration.

Presented here is a protocol for non-invasive mesenchymal stem cell (MSC) delivery and tracking in a mouse model of traumatic brain injury. Superparamagnetic iron oxide&#160;nanoparticles are employed as a magnetic resonance imaging (MRI) probe for MSC labeling and non-invasive in vivo tracking following intranasal delivery using real-time MRI.

Rastreamento de células-tronco mesenchymal rotuladas por óxido de ferro superparamagnético usando ressonância magnética após parto intranasal em um modelo de urina de urina de lesão cerebral traumática

Stem cell-based therapies for brain injuries, such as traumatic brain injury (TBI), are a promising approach for clinical trials. However, technical ...