Imaging pathological activities of human brain tissue in organotypic culture

Duigou, Caroline Le; Savary, Etienne; Morin‐Brureau, Mélanie; Gómez-Domínguez, Daniel; Sobczyk, André; Chali, Farah; Milior, Giampaolo; Kraus, Larissa; Meier, Jochen C.; Kullmann, Dimitri M.; Mathon, Bertrand; Prida, Liset Menéndez de la; Dorfmüller, Georg; Pallud, Johan; Eugène, Emmanuel; Clemenceau, Stéphane; Miles, Richard

doi:10.1016/j.jneumeth.2018.02.001

Cited by 39 publications

(49 citation statements)

References 51 publications

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“…Transgenes such as GCaMP6 (a Ca 2? indicator), carried by AAV or LV vectors and applied during culture preparation, can be stably expressed at 2 weeks-3 weeks, allowing simultaneous electrical and optical recordings of neuronal Ca 2? transients [43]. The findings described above show that, under suitable circumstances, resected human brain slices in culture can show long-term survival and enable experimental approaches such as transgene expression.…”

Section: Human Brain Slice Culturementioning

confidence: 90%

“…Extracellular population recording has revealed tonic and rhythmic network activity in human brain slices [41]. Furthermore, in hippocampal and temporal lobe slices, characteristic epileptiform activity can be maintained and recorded in vitro [42,43]. The in vitro spontaneous interictal-like activity recorded in the subiculum of human acute temporal lobe slice cultures appears to resemble intracranial EEG recordings from the same patient with temporal lobe epilepsy [44].…”

Section: Human Brain Slice Culturementioning

confidence: 99%

“…That study shows that optogenetics can become a practical tool to explore synaptic connectivity and neuronal networks in human brain tissue cultures. Recent work has explored the optimal conditions for long-term cultures of human brain slices for up to one month [43]. Studies have shown that the regional organization and neuronal physiology and morphology of the dentate gyrus, CA2/3, subiculum, and cortex surgically excised from the human temporal lobe and peri-tumoral or dysplastic cortex maintained for 5 weeks-6 weeks using a new defined culture medium are similar to acute slices, as indicated by immunohistochemistry, whole cell recording, and spontaneous synaptic events [43].…”

Section: Human Brain Slice Culturementioning

confidence: 99%

“…Recent work has explored the optimal conditions for long-term cultures of human brain slices for up to one month [43]. Studies have shown that the regional organization and neuronal physiology and morphology of the dentate gyrus, CA2/3, subiculum, and cortex surgically excised from the human temporal lobe and peri-tumoral or dysplastic cortex maintained for 5 weeks-6 weeks using a new defined culture medium are similar to acute slices, as indicated by immunohistochemistry, whole cell recording, and spontaneous synaptic events [43]. In contrast, some studies [25,27] have reported the emergence of reactive glial cells and concurrent degeneration of neurons in cultured resected brain tissue.…”

Section: Human Brain Slice Culturementioning

confidence: 99%

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Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

Verwer

Bao

et al. 2019

Neurosci. Bull.

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Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material. Keywords Alzheimer's disease Á Brain bank Á Brainderived neurotrophic factor Á Depression Á Electrical activity Á Human brain slice culture Á Neuropsychiatric disorders Á Organotypic culture Á Postmortem human brain tissue Á Resected human brain tissue Xin-Rui Qi and Ronald W. H. Verwer have contributed equally to this review.

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Section: Human Brain Slice Culturementioning

confidence: 90%

Section: Human Brain Slice Culturementioning

confidence: 99%

Section: Human Brain Slice Culturementioning

confidence: 99%

Section: Human Brain Slice Culturementioning

confidence: 99%

See 2 more Smart Citations

Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

Verwer

Bao

et al. 2019

Neurosci. Bull.

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“…They can be combined with organotypic cultures of cortical surgical samples given recent advances in protocols allowing for optimized transduction of transgenes and viral vector strategies. [16][17][18] Together, these 2 in vitro tools may transform the study of the human brain ex vivo in a more personalized way (Figure 1). Oscillations not only represent the basic functional mode of the brain but they are essential for a proper construction.…”

Section: Commentarymentioning

confidence: 99%

The Beauty and the Dish: Brain Organoids Go Active

Sánchez-Aguilera¹,

Prida²

2020

Epilepsy Curr

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GluK2 Is a Target for Gene Therapy in Drug‐Resistant Temporal Lobe Epilepsy

Boileau

Deforges

Peret

et al. 2023

Annals of Neurology

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ObjectiveTemporal lobe epilepsy (TLE) is characterized by recurrent seizures generated in the limbic system, particularly in the hippocampus. In TLE, recurrent mossy fiber sprouting from dentate gyrus granule cells (DGCs) crea an aberrant epileptogenic network between DGCs which operates via ectopically expressed GluK2/GluK5‐containing kainate receptors (KARs). TLE patients are often resistant to anti‐seizure medications and suffer significant comorbidities; hence, there is an urgent need for novel therapies. Previously, we have shown that GluK2 knockout mice are protected from seizures. This study aims at providing evidence that downregulating KARs in the hippocampus using gene therapy reduces chronic epileptic discharges in TLE.MethodsWe combined molecular biology and electrophysiology in rodent models of TLE and in hippocampal slices surgically resected from patients with drug‐resistant TLE.ResultsHere, we confirmed the translational potential of KAR suppression using a non‐selective KAR antagonist that markedly attenuated interictal‐like epileptiform discharges (IEDs) in TLE patient‐derived hippocampal slices. An adeno‐associated virus (AAV) serotype‐9 vector expressing anti‐grik2 miRNA was engineered to specifically downregulate GluK2 expression. Direct delivery of AAV9‐anti grik2 miRNA into the hippocampus of TLE mice led to a marked reduction in seizure activity. Transduction of TLE patient hippocampal slices reduced levels of GluK2 protein and, most importantly, significantly reduced IEDs.InterpretationOur gene silencing strategy to knock down aberrant GluK2 expression demonstrates inhibition of chronic seizure in a mouse TLE model and IEDs in cultured slices derived from TLE patients. These results provide proof‐of‐concept for a gene therapy approach targeting GluK2 KARs for drug‐resistant TLE patients. ANN NEUROL 2023

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Imaging pathological activities of human brain tissue in organotypic culture

Cited by 39 publications

References 51 publications

Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

Human Brain Slice Culture: A Useful Tool to Study Brain Disorders and Potential Therapeutic Compounds

The Beauty and the Dish: Brain Organoids Go Active

GluK2 Is a Target for Gene Therapy in Drug‐Resistant Temporal Lobe Epilepsy

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