Ricerc@Sapienza

Erythropoietin (EPO)is a hematopoietic growth factor that has an important role in the erythropoiesis. EPO and its receptor (EPO-R)are expressed all over in the mammalian brain. Furthermore, it has been reported that EPO may exert neuroprotective effect in animal models of brain disorders as ischemia and epilepsy. Here, we investigate whether EPO could modulate the GABA-evoked currents (I GABA )in both human epileptic and non-epileptic control brain tissues.

The association between epilepsy and neurodevelopmental diseases is well-recognized and has gained significant attention in the field of neuroscience in recent years. One of the main reasons for this interest is the need for a better understanding of the events that lead to the development and maturation of the CNS. This is a fundamental and necessary basis for potential breakthrough strategies that could guide novel and more effective disease-modifying therapeutic approaches to neurodevelopmental syndromes that are frequently characterized by severe and

We compared GABAergic function and neuronal excitability in the hippocampal tissue of seven sporadic MTLE patients with a patient carrying a SCN1A loss-of-function mutation. All had excellent outcome from anterior temporal lobectomy, and neuropathological study always showed characteristic hippocampal sclerosis (Hs). Compared to MTLE patients, there was a more severe impairment of GABAergic transmission, due to the lower GABAergic activity related to the NaV1.1 loss-of-function, in addition to the typical GABA-current rundown, a hallmark of sporadic MTLE.

Introduction: Several drugs targeting the GABAergic system are used in the treatment of epilepsy, but only one drug targeting glutamate receptors is on the market. This is surprising because an imbalance between excitatory and inhibitory neurotransmission lies at the core of the pathophysiology of epilepsy. One possible explanation is that drug development has been directed towards the synthesis of molecules that inhibit the activity of ionotropic glutamate receptors.

A variety of evidence suggested that an imbalance in excitatory and inhibitory neurotransmission could be one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Understanding the causes of this imbalance may provide essential insight into the basic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Accordingly, GABA is the most important inhibitory neurotransmitter in the CNS and its receptors (e.g., GABAARs) can still be relevant targets of new antiepileptic drugs (AEDs).
BACKGROUND:

Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance.

A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets.

Objectives: Thrombospondins, which are known to interact with the ?2? subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans.

Epilepsy is a complex clinical condition characterized by repeated spontaneous seizures. Seizures have been linked to multiple drivers including DNA damage accumulation. Investigation of epilepsy physiopathology in humans imposes ethical and practical limitations, for this reason model systems are mostly preferred. Among animal models, mouse mutants are particularly valuable since they allow conjoint behavioral, organismal, and genetic analyses.

Introduction. Epilepsy is a common neurological disease requiring complex therapies, which have been unable to achieve seizure control in 30% of patients. Poor adherence has been recognized as a possible determinant of drug-resistance. Prolonged-release formulations of anti-epileptic drugs might help increase adherence, minimize side effects and pharmacological interactions. Areas Covered. Pregabalin (PGB) has peculiar pharmacodynamics and almost ideal pharmacokinetics, except for a short half-life and therefore requiring multiple daily dosing.