Multimodal approach to characterize surgically removed epileptogenic zone from patients with focal drug-resistant epilepsy: from operating room to wet lab DOI Creative Commons
Jenni Kyyriäinen, Adriana Della Pietra, Mastaneh Torkamani-Azar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 20, 2025

ABSTRACT Objective We have established a comprehensive sample handling protocol designed for the multiscale assessment of epileptogenic tissue. This aims to identify novel therapeutic targets and enhance diagnosis stratification patients with drug-resistant epilepsy, thereby optimizing their treatment anti-seizure medications surgical interventions. Methods Patients focal recommended treatment, are recruited after detailed multidisciplinary preoperative evaluation at Epilepsy Center Kuopio University Hospital in Finland. A day before resective surgery, undergo magnetic resonance imaging (MRI) including advanced methodologies. During each piece resected tissue is placed under oxygenation on ice-cold artificial cerebral spinal fluid-solution. The pieces then immediately transported laboratory, assessed by neuropathologist, sliced both clinical research. Two adjacent slices provided research sent Eastern Results developed provides opportunity characterization from same patient using emerging imaging, electrophysiology, molecular biology technologies. optimized conditions preserving alive electrophysiological measurements simultaneously making possible ex vivo studies multi-omics acquisition, electron microscopy, histology, MRI. Our enables mapping functional readouts structural alterations human goal integrate multimodal data co-register tissues within whole brain’s MRI space. approach localization zones refine identifying abnormalities global connectivity patterns. Significance successfully systematic collection analysis data. elucidate structural, functional, characteristics that render epileptogenic, enhancing subsequent care epilepsy. Key points Introducing assess epileptogenicity levels. integrating technology properties obtain patient-specific Correlation predict pathology

Язык: Английский

Synaptic neoteny of human cortical neurons requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition DOI Creative Commons
Baptiste Libé‐Philippot, Ryohei Iwata, Aleksandra J. Recupero

и другие.

Neuron, Год журнала: 2024, Номер 112(21), С. 3602 - 3617.e9

Опубликована: Окт. 14, 2024

Human-specific (HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear. Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic SRGAP2A, cortical pyramidal neurons (CPNs) xenotransplanted mouse cortex. Downregulation SRGAP2B/C CPNs led to strongly accelerated development, indicating requirement for neoteny that distinguishes synaptogenesis. promoted by reducing levels SRGAP2A,thereby increasing postsynaptic accumulation SYNGAP1 protein, encoded a major intellectual disability/autism spectrum disorder (ID/ASD) gene. Combinatorial loss-of-function experiments vivo revealed tempo synaptogenesis is set reciprocal antagonism between SRGAP2A SYNGAP1, which tipped toward SRGAP2B/C. Thus, can modify phenotypic expression genetic mutations leading ID/ASD through regulation neoteny.

Язык: Английский

Процитировано

4
Multimodal approach to characterize surgically removed epileptogenic zone from patients with focal drug-resistant epilepsy: from operating room to wet lab DOI Creative Commons
Jenni Kyyriäinen, Adriana Della Pietra, Mastaneh Torkamani-Azar

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 20, 2025

ABSTRACT Objective We have established a comprehensive sample handling protocol designed for the multiscale assessment of epileptogenic tissue. This aims to identify novel therapeutic targets and enhance diagnosis stratification patients with drug-resistant epilepsy, thereby optimizing their treatment anti-seizure medications surgical interventions. Methods Patients focal recommended treatment, are recruited after detailed multidisciplinary preoperative evaluation at Epilepsy Center Kuopio University Hospital in Finland. A day before resective surgery, undergo magnetic resonance imaging (MRI) including advanced methodologies. During each piece resected tissue is placed under oxygenation on ice-cold artificial cerebral spinal fluid-solution. The pieces then immediately transported laboratory, assessed by neuropathologist, sliced both clinical research. Two adjacent slices provided research sent Eastern Results developed provides opportunity characterization from same patient using emerging imaging, electrophysiology, molecular biology technologies. optimized conditions preserving alive electrophysiological measurements simultaneously making possible ex vivo studies multi-omics acquisition, electron microscopy, histology, MRI. Our enables mapping functional readouts structural alterations human goal integrate multimodal data co-register tissues within whole brain’s MRI space. approach localization zones refine identifying abnormalities global connectivity patterns. Significance successfully systematic collection analysis data. elucidate structural, functional, characteristics that render epileptogenic, enhancing subsequent care epilepsy. Key points Introducing assess epileptogenicity levels. integrating technology properties obtain patient-specific Correlation predict pathology

Язык: Английский

Процитировано

0