Epilepsy is a chronic neurological disease characterized by involuntary and sudden epileptic seizures. It affects about 60 million people worldwide. In Italy, there are about 500,000 people with epilepsy, with an increase of 30,000 cases per year. People affected by this disease are exposed to a greater risk of mortality, cognitive deficits, manifestations of anxiety and depression. Today, there are over 20 drugs used to control seizures. Unfortunately, these drugs are not able to prevent or block the development of the disease. In 30% of people with epilepsy, the available drugs do not control seizures which are therefore defined as drug-resistant.
Our research activity is translational, therefore, it is focused on the discovery of pathological mechanisms underlying the disease onset and progression for the development of novel therapies to provide not only a symptomatic control of seizures but also to interfere with epileptogenesis. Epileptogenesis is the pathologic brain process causing the generation and recurrence of seizures and the progression of the disease which may include neuronal cell loss, neurological comorbidities and drug resistance.
Role of neuroinflammation
The study focuses on the identification of neuroinflammatory mechanisms that may contribute to the generation of epileptic seizures in rodent models of structural (acquired or genetic) epilepsies. The aim is to interfere with such pathologic mechanisms with novel or re-purposed drugs for improving the disease course and decrease the burden of seizures or prevent their generation. Additional outcome measures include neuronal cell loss and cognitive deficits. These studies are based on the use of rodent models of acquired epilepsies mimicking pediatric and adult forms of epilepsy.
Role of resolution mechanisms of neuroinflammation
Emerging experimental and clinical evidence indicates a reduced and inefficient resolution response to neuroinflammation in the brain undergoing epileptogenesis. This impaired anti-inflammatory homeostatic response may be responsible for the pathologic consequences of neuroinflammation in epilepsy. The study focuses on identifying the causes of this impaired resolution response and on strategies for improving this response with dietary or pharmacological interventions. The Focus of the research is on anti-inflammatory lipids and proteins such as IL-1 receptor antagonist and IL-10.
Characterization and validation of biomarkers
It is necessary to discover and validate biomarkers for epilepsy which are still lacking. In particular, we aim at characterizing novel prognostic biomarkers useful to stratify patients at high risk of developing epilepsy in clinical studies, and predictive biomarkers sensitive to therapeutic effects of drugs. Using animal models aligned with prospective clinical studies in symptomatic epilepsies (for example, patients with neurotrauma), we apply MRI-based molecular neuroimaging techniques, electroencephalography for analysis of brain activity, behavioral tests and measurements of blood molecules in longitudinal studies during the development of epilepsy.
Role of the gut-microbiota-brain axis in epilepsy
Emerging experimental and clinical evidence supports the pathogenetic role of the gut-microbiota-brain axis in epilepsy. Using experimental models of epilepsy, this project evaluates gut structural and molecular changes and dysfunctions, and studies the microbiota during disease development with metagenomic and metabolomic approaches. We also study whether pharmacological treatments that specifically target microbiota-gut-brain axis prevent or delay the onset of epilepsy, and/or reduce the frequency of spontaneous seizures and comorbidities by normalizing intestinal dysbiosis, and inhibiting inflammation and oxidative stress in the intestine. This study may allow to identify the intestine as a novel target for treating epilepsy.
International Consensus on Cardiopulmonary Resuscitation.