The mechanisms that transform a normal brain to an epileptic one are not fully understood. Interleukin-1 beta (IL-1beta) contributes to neuronal degeneration observed in several neurological disorders and recently has been implicated in neuronal injury that may accompany the process of epileptogenesis. This review presents the hypothesis that IL-1beta may contribute to the development of epilepsy via several mechanisms, including classical effects on neuronal survival and transcription pathways; novel rapid effects on receptor-gated ion channels; and long-lasting effects on expression of selective gene families. Thus, evidence that IL-1beta actions in epilepsy can be independent from the neurotoxic effects of this cytokine is presented.

The contribution of neuroinflammatory processes to epilepsy that may follow febrile status epilepticus (FSE) is crucial, as inflammatory mediators offer targets for prevention and intervention strategies. Experimental models suggest that neuroinflammation contributes intrinsically to the generation of fever-related seizures in children. FSE, defined as prolonged febrile seizures (FS), often precedes and likely contributes to a significant subset of adult temporal lobe epilepsy (TLE). Because TLE may be associated with cognitive and emotional problems and is commonly refractory to treatment, unraveling the connections between FSE and TLE and specifically the role of neuroinflammation and related epigenomic mechanisms is of significant translational value. This chapter discusses the contribution of inflammatory mediators to FS and FSE and then focuses on evidence from experimental models for involvement of inflammatory pathways in FSE-related epileptogenesis. Capitalizing on information from both human studies and animal models, we discuss the potential contributions of several salient neuroinflammatory cascades, as well as of blood-brain barrier disruption, microRNAs, and downstream transcriptional regulators, in the context of FSE and epileptogenesis in general. Finally, we highlight the potential efficacy of both pathway-specific blockers and global antiinflammatory strategies for mitigating FSE-related epileptogenesis.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis.

The relationship between financing constraints, investments in research and development (R&D) and innovative performances has recently attracted renewed attention in the aftermath of a financial crisis that has led to problems of access to the credit on which innovation activities crucially rely. In spite of past developments in the theoretical analysis and in the data and methodologies for empirical investigation, some issues have remained unexplored to date. In this introduction to the special issue, we examine the contribution of the papers it contains, which provide new conceptualisations and empirical evidence at the firm level for Europe. Most previous research results, which were mainly based on extending models of financing constraints and physical investments to R&D investments, are confirmed, while new insights about this relationship are uncovered, in terms of the structural characteristics of the constrained firms, of the industries in which they operate, of their innovative activities and of the innovation outcomes they achieve.

Fever can provoke "febrile" seizures (FS). Because complex FS may promote development of temporal lobe epilepsy, understanding their mechanisms is clinically important. Using an immature rodent model and transgenic technology, we examined the role of interleukin-1beta, (IL-1beta), a pyrogenic, proinflammatory cytokine, in FS. IL-1beta receptor-deficient mice were resistant to experimental FS. This resistance appeared independent of genetic background and was attributed to lack of IL-1beta signaling, because exogenous cytokine reduced seizure threshold in wild-type but not receptor-deficient mice independent of strain. In addition, high IL-1beta doses induced seizures only in IL-1beta receptor-expressing mice. These data indicate that IL-1beta signaling contributes critically to fever-induced hyperexcitability underlying FS, constituting a potential target for their prevention.

This monograph summarizes one of the sessions of the XI Workshop on Neurobiology of Epilepsy (WONOEP), and provides a critical review of the current state of the field. Speakers and discussants focused on several broad topics: (1) the coexistence of inflammatory processes encompassing several distinct signal-transduction pathways with the epileptogenic process; (2) evidence for the contribution of specific inflammatory molecules and processes to the onset and progression of epilepsy, as well as to epilepsy-related morbidities including depression; (3) the complexity and intricate cross-talk of the pathways involved in inflammation, and the discrete, often opposite roles of a given mediator in neurons versus other cell types. These complexities highlight the challenges confronting the field as it aims to define inflammatory molecules as promising targets for epilepsy prevention and treatment.

A biomarker is defined as an objectively measured characteristic of a normal or pathologic biologic process. Identification and proper validation of biomarkers of epileptogenesis (the development of epilepsy) and ictogenesis (the propensity to generate spontaneous seizures) might predict the development of an epilepsy condition; identify the presence and severity of tissue capable of generating spontaneous seizures; measure progression after the condition is established; and determine pharmacoresistance. Such biomarkers could be used to create animal models for more cost-effective screening of potential antiepileptogenic and antiseizure drugs and devices, and to reduce the cost of clinical trials by enriching the trial population, and acting as surrogate markers to shorten trial duration. The objectives of the biomarker subgroup for the London Workshop were to define approaches for identifying possible biomarkers for these purposes. Research to identify reliable biomarkers may also reveal underlying mechanisms that could serve as therapeutic targets for the development of new antiepileptogenic and antiseizure compounds.