An in vitro model of neurotrauma in organotypic spinal cord cultures from adult mice

Krassioukov, Andrei V.; Ackery, Alun; Schwartz, Gwen; Adamchik, Yana; Liu, Yang; Fehlings, Michael G.

doi:10.1016/s1385-299x(02)00180-0

Cited by 75 publications

(64 citation statements)

References 13 publications

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“…In vivo models necessitate the use of analgesia and rigorous post-operative monitoring of animals, which must be housed individually [8]. The requirements for specialist staff and infrastructure in particular, place major financial constraints on such work [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…These models offer several advantages including the ease of manipulation/observation of in vitro preparations [18]; several ages, neuroanatomical areas and species, including human foetuses [23] and transgenic models [24,25] can be used as tissue donor sources, offering high flexibility to study neural pathologies and disease mechanisms. Slice cultures are amenable to electrophysiological techniques [26], molecular biology methods [27], time lapse video microscopy [28] and dynamic confocal imaging [10,29,30], which has greatly expanded the translational utility of this approach. Clearly therefore, such models have wide applicability to a range of tissues and pathologies.…”

Section: Introductionmentioning

confidence: 99%

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An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, biocompatibility, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a novel solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofiber meshes (± poly-lysine + laminin coating) within injury sites using a lightweight

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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“…A few different approaches have been taken to mimic SCI pathology in vitro including: monoculture systems (primary and cell lines), co-culture systems, microfluidic devices and organotypic slice cultures [31][32][33][34][35][36][37]. A number of factors must be taken into consideration when evaluating the utility of each model system including the ability to mimic intercellular uptake dynamics, definition of cellular ratios to model specific CNS regions/disease states, standardisation of protein coronas around introduced nanoparticles, ease of nanoparticle delivery, and amenability to various (including real-time) imaging techniques [9].…”

Section: Discussionmentioning

confidence: 99%

“…However, two of these models were established by weight drop onto slices, which is not suitable for assessing NP uptake in clearly-demarcated lesion sites, and while these models mimicked some of the responses to injury in vivo overall the characterisation of pathology was basic (e.g. cell death) [33,36]. Another SCI model has been established based on induction of complete transecting injury in parasagittal organotypic spinal cord slices from neonatal mice [23].…”

Section: Discussionmentioning

confidence: 99%

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

2016

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Development of nanoparticle (NP) based therapies to promote regeneration in sites of central nervous system (CNS; i.e. brain and spinal cord) pathology relies critically on the availability of experimental models that offer biologically valid predictions of NP fate in vivo. However, there is a major lack of biological models that mimic the pathological complexity of target neural sites in vivo, particularly the responses of resident neural immune cells to NPs. Here, we have utilised a previously developed in vitro model of traumatic spinal cord injury (based on 3-D organotypic slice arrays) with dynamic time lapse imaging to reveal in real-time the acute cellular fate of NPs within injury foci. We demonstrate the utility of our model in revealing the well documented phenomenon of avid NP sequestration by the intrinsic immune cells of the CNS (the microglia). Such immune sequestration is a known translational barrier to the use of NP-based therapeutics for neurological injury. Accordingly, we suggest that the utility of our model in mimicking microglial sequestration behaviours offers a valuable investigative tool to evaluate strategies to overcome this cellular response within a simple and biologically relevant experimental system, whilst reducing the use of live animal neurological injury models for such studies.

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“…Existe um expressivo interesse em reconhecer e entender os mecanismos de degeneração e reparo neuronais, o que pode proporcionar base para o desenvolvimento e a implementação de novas estratégias terapêuticas e aumentar as chances de sucesso na recuperação dos pacientes (Dumont et al, 2002;Kwon et al, 2005;Thuret et al, 2006). Diferentes modelos in vivo são utilizados para reproduzir lesão medular experimentalmente (Krassioukov et al, 2002). Dentre eles, um dos mais utilizados tem sido a produção de trauma compressivo por peso em ratos (Basso et al, 1996;Carlson et al, 1998;Farooque, 2000;Gaviria et al, 2000;Ma et al, 2001).…”

Section: Introductionunclassified

Modelo experimental de trauma medular agudo produzido por aparelho estereotáxico modificado

Torres¹,

Silva²,

Almeida³

et al. 2010

Arq. Bras. Med. Vet. Zootec.

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RESUMOForam utilizados 55 ratos machos da espécie Rattus novergicus, variedade Wistar, com o objetivo de propor um modelo experimental de trauma medular produzido por aparelho estereotáxico modificado, capaz de reproduzir clinicamente lesões medulares padronizadas. Após realização de laminectomia dorsal de T13, utilizou-se peso compressivo de 50,5g (25 animais -grupo I) ou 70,5g (30 animais -grupo II), durante cinco minutos, comprimindo a medula espinhal. Os animais foram assistidos durante oito dias, por meio de testes comportamentais para avaliar a sensibilidade dolorosa, a capacidade motora, o posicionamento tátil e proprioceptivo e a capacidade de manter-se em plano inclinado. No grupo I, observaram-se déficits neurológicos moderados e transitórios, que variaram entre os animais. No grupo II, foi possível obter um trauma padronizado, caracterizado por paraplegia bilateral e simétrica dos membros posteriores, perda de propriocepção e da sensibilidade dolorosa de todos os animais. A utilização do aparelho estereotáxico desenvolvido permite reproduzir clinicamente trauma medular padronizado em ratos, de maneira simples, econômica e satisfatória, o que poderá proporcionar avanços nas investigações terapêuticas, abrangendo doenças neurodegenerativas, como é o caso do trauma medular agudo. Palavras

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An in vitro model of neurotrauma in organotypic spinal cord cultures from adult mice

Cited by 75 publications

References 13 publications

An in vitro spinal cord injury model to screen neuroregenerative materials

An in vitro spinal cord injury model to screen neuroregenerative materials

Using a 3-D multicellular simulation of spinal cord injury with live cell imaging to study the neural immune barrier to nanoparticle uptake

Modelo experimental de trauma medular agudo produzido por aparelho estereotáxico modificado

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