Organotypic vibrosections: Novel whole sagittal brain cultures

Ullrich, Celine; Daschil, Nina; Humpel, Christian

doi:10.1016/j.jneumeth.2011.07.021

Cited by 42 publications

(49 citation statements)

References 37 publications

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“…In the present work, brain sagittal slices were used since they contain in a unique slice many anatomical structures as corpus callosum, cortex, hippocampus, striatum, globus pallidus, SN and cerebellum among others. In addition, many of the original neuronal connections between brain structures are better preserved in brain sagittal slices (Ullrich et al, 2011). Furthermore, the subgranular zone of the dentate gyrus and the subventricular zone, two neural stem cell niches, are conserved which allows to study neurogenesis (Garzon-Muvdi and Quinones-Hinojosa, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the subgranular zone of the dentate gyrus and the subventricular zone, two neural stem cell niches, are conserved which allows to study neurogenesis (Garzon-Muvdi and Quinones-Hinojosa, 2009). Sagittal sections remain the most complete type of organotypic slices since they allow the observation of cholinergic, GABAergic and dopaminergic neurons as well as of vascular brain capillaries or cortico-striatal and cortico-hippocampal nerve fibers (Kearns et al, 2006; Ullrich et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

“…However, as in animal models, 6-OHDA led to neuronal death mediated by oxidative stress inducing selective dopaminergic neuron degeneration but did not produce extra-nigral pathology or Lewy body-like inclusions (Schober, 2004; Cavaliere and Matute, 2011). More recently, whole rat brain sagittal organotypic slices were developed which maintained dopaminergic and cholinergic neurons, as well as a complex capillary network and long nerve fibers (Ullrich et al, 2011). In the same way, sagittal sections of mouse brain were performed.…”

Section: Introductionmentioning

confidence: 99%

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Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

et al. 2014

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Parkinson’s disease (PD) is the second most frequent neurodegenerative disorder afflicting 2% of the population older than 65 years worldwide. Recently, brain organotypic slices have been used to model neurodegenerative disorders, including PD. They conserve brain three-dimensional architecture, synaptic connectivity and its microenvironment. This model has allowed researchers a simple and rapid method to observe cellular interactions and mechanisms. In the present study, we developed an organotypic PD model from rat brains that includes all the areas involved in the nigrostriatal pathway in a single slice preparation, without using neurotoxins to induce the dopaminergic lesion. The mechanical transection of the nigrostriatal pathway obtained during slice preparation induced PD-like histopathology. Progressive nigrostriatal degeneration was monitored combining innovative approaches, such as diffusion tensor magnetic resonance imaging (DT-RMI) to follow fiber degeneration and mass spectrometry to quantify striatal dopamine content, together with bright-field and fluorescence microscopy imaging. A substantia nigra dopaminergic cell number decrease was observed by immunohistochemistry against rat tyrosine hydroxylase (TH) reaching 80% after 2 days in culture associated with a 30% decrease of striatal TH-positive fiber density, a 15% loss of striatal dopamine content quantified by mass spectrometry and a 70% reduction of nigrostriatal fiber fractional anisotropy quantified by DT-RMI. In addition, a significant decline of medium spiny neuron density was observed from days 7 to 16. These sagittal organotypic slices could be used to study the early stage of PD, namely dopaminergic degeneration, and the late stage of the pathology with dopaminergic and GABAergic neuron loss. This novel model might improve the understanding of PD and may represent a promising tool to refine the evaluation of new therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

et al. 2014

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“…The hyperphosphorylated form of tau is known to form intraneuronal neurofibrillary tangles (NFTs) (22). An increasingly accepted hypothesis of toxicity argues that tau oligomers which appear in the initial phases of tangle formation are the most toxic species (23)(24)(25)(26)(27)(28)(29)(30)(31). Recently published works support the idea that prefibrillar soluble oligomers of amyloidogenic proteins, including α-synuclein and amyloid-beta (Aβ) are more toxic than insoluble LBs and senile plaques (32)(33)(34)(35)(36)(37)(38).…”

Section: Introductionmentioning

confidence: 99%

Pathological Interface Between Oligomeric Alpha-Synuclein and Tau in Synucleinopathies

Sengupta

Guerrero-Muñoz

Castillo-Carranza

et al. 2015

Biological Psychiatry

144

134

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“…For example, Humpel group used sagittal brain slices, and for the first time showed that dopamine neurons survive despite the non-functional striatonigral pathway. [117] Organotypic hippocampal slice cultures represent a good model for studying AD pathology, given that the hippocampal is a strategic region in AD patients that exhibits early neurodegeneration. [114,118] Several groups also used this model as widely accepted platform to study A β toxicity.…”

Section: Recapitulating the Human Brain Pathophysiologymentioning

confidence: 99%

Three‐Dimensional Models of the Human Brain Development and Diseases

Jorfi

D’Avanzo

Kim

et al. 2017

Adv Healthcare Materials

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Deciphering the human brain pathophysiology remains one of the greatest challenges of the 21st century. Neurological disorders represent a significant proportion of diseases burden; however, the complexity of the brain physiology makes it challenging to model its diseases. Simple in vitro models have been very useful for precise measurements in controled conditions. However, existing models are limited in their ability to replicate complex interactions between various cells in the brain. Studying human brain requires sophisticated models to reconstitute the tangled architecture and functions of brain cells. Recently, advances in the development of three-dimensional (3D) brain cell culture models have begun to recapitulate various aspects of the human brain physiology in vitro and replicate basic disease processes of Alzheimer’s disease, amyotrophic lateral sclerosis, and microcephaly. In this review, we discuss the progress, advantages, limitations, and future directions of 3D cell culture systems for modeling the human brain development and diseases.

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Organotypic vibrosections: Novel whole sagittal brain cultures

Abstract: Highlights► Novel whole brain sagittal organotypic vibrosection in vitro model. ► Survival of cholinergic and dopaminergic neurons. ► Capillaries in whole brain sections in vitro. ► Long nerve fiber growth with neurotracing (Mini-Ruby). ► Striato-nigral varicosities.

Cited by 42 publications

References 37 publications

Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease

Pathological Interface Between Oligomeric Alpha-Synuclein and Tau in Synucleinopathies

Three‐Dimensional Models of the Human Brain Development and Diseases

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