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Acute Brain and Cardiovascular Injury

Laboratory of Epilepsy and Therapeutic Strategies

Head
Annamaria
Vezzani
Head of Laboratory
Acute Brain and Cardiovascular Injury
annamaria.vezzani@marionegri.it
Senior Advisor
No items found.

Epilepsy is a chronic neurological disorder characterized by involuntary and sudden epileptic seizures. It affects around 60 million people worldwide. In Italy alone, there are approximately 500,000 people with epilepsy, with an increase of 30,000 new cases per year. People affected by this disease are at greater risk of mortality, cognitive deficits, manifestations of anxiety and depression.

Today, there are over 20 drugs used to control epileptic seizures. Unfortunately, these medications are unable to prevent or stop the progression of the disease. Furthermore, in 30% of people with epilepsy, the available medications do not control seizures, which are therefore classified as drug-resistant.

Our research activity is translational, therefore it focuses on the discovery and development of novel therapies not only to provide a symptomatic control of seizures, but also to interfere with epileptogenesis, the pathologic brain process causing complex molecular, structural, and functional changes that occur in the brain and lead to the onset and recurrence of epileptic seizures, as well as various neurological deficits and comorbidities, neuronal cell loss and drug resistance.

RESEARCH AREAS

Role of neuroinflammation

Our studies focus on identifying inflammatory mechanisms that may contribute to the generation of epileptic seizures, neurodegenerative phenomena, and cognitive deficits that characterize drug-resistant epilepsy. The goal is to intervene on the inflammatory pathophysiological mechanisms, with novel or re-purposed drugs, to improve the disease course, reducing epileptic seizures and making them sensitive to anticonvulsant medications, reducing neuronal damage and neurological comorbidities. The study, therefore, focuses on the molecular and cellular characterization of these mechanisms and later on pharmacological interventions targeting various stages of the disease, using rodent models of acquired epilepsy.

Role of resolving molecules in the neuroinflammatory process

Emerging experimental and clinical evidence indicates a reduced (and inefficient) endogenous response to neuroinflammation in the brain undergoing epileptogenesis. This impaired anti-inflammatory homeostatic response may significantly contribute to the pathological consequences of neuroinflammation in epilepsy. The study focuses on identifying the causes of this impaired resolution response and the strategies to improve this response with dietary or pharmacological treatments, providing a therapeutic effect. The research focuses on endogenous anti-inflammatory molecules, such as IL-1 receptor antagonists, IL-10, and lipids derived from fatty acid metabolism.

Characterization and validation of biomarkers

It is necessary to characterize and validate new non-invasive biomarkers in epilepsy such as prognostic biomarkers (aimed at preventing disease progression and allowing the stratification of patients enrolled in clinical studies), or pharmacodynamic biomarkers (that can predict the therapeutic response to a new treatment). Using animal models of neurotrauma—and of symptomatic epilepsy more in general—the study, carried out in collaboration with the Laboratory of Traumatic Brain Injury and Neuroprotection, aims to apply new molecular neuroimaging techniques (with magnetic resonance imaging), electroencephalography, behavioral tests, and measurements of protein molecules in the blood for longitudinal analyses during the development of the disease in models that replicate the clinical condition.

Role of the gut-microbiota-brain axis in epilepsy

Emerging experimental and clinical evidence supports the pathogenic role of the gut-microbiota-brain axis in epilepsy. Using experimental models of epilepsy, this project aims to evaluate structural and molecular changes in the gut and gut dysbiosis through metagenomic and metabolomic studies. Additionally, it investigates whether pharmacological treatments that specifically target the microbiota-gut-brain axis can prevent or delay the onset of epilepsy, and/or reduce the frequency of drug-resistant epileptic seizures and comorbidities by normalizing gut dysbiosis and inhibiting inflammation and oxidative stress in the gut. Findings from this study could establish the gut as a novel pharmacological target for treating epilepsy.

Head Unit
Teresa Giovanna
Ravizza
Head of Unit
teresa.ravizza@marionegri.it
Staff
Akash
Bera
Researcher
akash.bera@marionegri.it
Francesca
Buffelli
Researcher
francesca.buffelli@marionegri.it
Massimo
Rizzi
Researcher
massimo.rizzi@marionegri.it
Rossella
Di Sapia
Researcher
rossella.disapia@marionegri.it
Sneha
Anand
Researcher
sneha.anand@marionegri.it
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Head
Annamaria
Vezzani
Head of Laboratory
Acute Brain and Cardiovascular Injury
annamaria.vezzani@marionegri.it
Senior Advisor
No items found.

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