Topic: epileptogenesis

The epileptogenesis process is associated with large-scale changes in gene expression, which contribute to the remodelling of brain networks permanently altering excitability. About 80% of the protein coding genes are under the influence of the circadian rhythms. These are 24-hour endogenous rhythms that determine a large number of daily changes in physiology and behavior in our bodies. In the brain, the master clock regulates a large number of pathways that are important during epileptogenesis and established-epilepsy, such as neurotransmission, synaptic homeostasis, inflammation, blood-brain

Epileptogenesis is a gradual and dynamic process leading to difficult-to-treat seizures. Several cellular, molecular, and pathophysiologic mechanisms, including the activation of inflammatory processes. The use of human brain tissue represents a crucial strategy to advance our understanding of the underlying neuropathology and the molecular and cellular basis of epilepsy and related cognitive and behavioral comorbidities, The mounting evidence obtained during the past decade has emphasized the critical role of inflammation in the pathophysiological processes implicated in a large spectrum o

How seizures emerge from the abnormal dynamics of neural networks within the epileptogenic tissue remains an enigma. Are seizures random events, or do detectable changes in brain dynamics precede them? Are mechanisms of seizure emergence identical at the onset and later stages of epilepsy? Is the risk of seizure occurrence stable, or does it change over time? A myriad of questions about seizure genesis remains to be answered to understand the core principles governing seizure genesis. The last decade has brought unprecedented insights into the complex nature of seizure emergence. It is now bel

The origins, mechanisms and consequences of epilepsy in the developing brain are incompletely understood. Many developmental epilepsies have a genetic basis and their mechanisms stem from deficits in the function of one or numerous genes. Others, such as those that follow prolonged febrile seizures or severe birth asphyxia in a ‘normal’ brain may depend on the interaction of the insult with the rapidly evolving brain cells and circuits. Yet, how early-life insults may provoke epilepsy is unclear, and requires multiple levels of analysis: behavior, circuits, cells [neurons, glia] and molecules.

Traumatic brain injury (TBI), a leading cause of acquired epilepsy, results in primary cellular injury as well as secondary neurophysiological and inflammatory responses which contribute to epileptogenesis. I will present our recent studies identifying a role for neuro-immune interactions, specifically, the innate immune receptor Toll-like receptor 4 (TLR4), in enhancing network excitability and cell loss in hippocampal dentate gyrus early after concussive brain injury. I will describe results indicating that the transient post-traumatic increases in dentate neurogenesis which occurs during th

Malformations of cortical development (MCDs) result from alterations of one or combined developmental steps, including progenitors proliferation, neuronal migration and differentiation. They are important cause of childhood epilepsy and frequently associate cognitive deficits and behavioral alterations. Though the genetic basis of MCDs have known prominent progress during the past decade, including the identification of somatic, mosaic mutations responsible for focal MCDs, the pathophysiological mechanisms linking malformations to epileptogenesis remain elusive. In this seminar I will present

Glioblastoma cells trigger pharmacoresistant seizures that may promote tumor growth and diminish the quality of remaining life. To define the relationship between growth of glial tumors and their neuronal microenvironment, and to identify genomic biomarkers and mechanisms that may point to better prognosis and treatment of drug resistant epilepsy in brain cancer, we are analyzing a new generation of genetically defined CRISPR/in utero electroporation inborn glioblastoma (GBM) tumor models engineered in mice. The molecular pathophysiology of glioblastoma cells and surrounding neurons and untra