Traumatic brain injury is a major economic burden to hospitals in terms of emergency department visits, hospitalizations, and utilization of intensive care units. Current guidelines for the management of severe traumatic brain injuries are primarily supportive, with an emphasis on surveillance (i.e. intracranial pressure) and preventive measures to reduce morbidity and mortality. There are no direct effective therapies available. Over the last fifteen years, pre-clinical studies in regenerative medicine utilizing cell-based therapy have generated enthusiasm as a possible treatment option for traumatic brain injury. In these studies, stem cells and progenitor cells were shown to migrate into the injured brain and proliferate, exerting protective effects through possible cell replacement, gene and protein transfer, and release of anti-inflammatory and growth factors. In this work, we reviewed the pathophysiological mechanisms of traumatic brain injury, the biological rationale for using stem cells and progenitor cells, and the results of clinical trials using cell-based therapy for traumatic brain injury. Although the benefits of cell-based therapy have been clearly demonstrated in pre-clinical studies, some questions remain regarding the biological mechanisms of repair and safety, dose, route and timing of cell delivery, which ultimately will determine its optimal clinical use.

Our understanding of the genetic aetiology of paediatric epilepsies has grown substantially over the last decade. However, in order to translate improved diagnostics to personalised treatments, there is an urgent need to link molecular pathophysiology in epilepsy to whole-brain dynamics in seizures. Zebrafish have emerged as a promising new animal model for epileptic seizure disorders, with particular relevance for genetic and developmental epilepsies. As a novel model organism for epilepsy research they combine key advantages: the small size of larval zebrafish allows high throughput in vivo experiments; the availability of advanced genetic tools allows targeted modification to model specific human genetic disorders (including genetic epilepsies) in a vertebrate system; and optical access to the entire central nervous system has provided the basis for advanced microscopy technologies to image structure and function in the intact larval zebrafish brain. There is a growing body of literature describing and characterising features of epileptic seizures and epilepsy in larval zebrafish. Recently genetically encoded calcium indicators have been used to investigate the neurobiological basis of these seizures with light microscopy. This approach offers a unique window into the multiscale dynamics of epileptic seizures, capturing both whole-brain dynamics and single-cell behaviour concurrently. At the same time, linking observations made using calcium imaging in the larval zebrafish brain back to an understanding of epileptic seizures largely derived from cortical electrophysiological recordings in human patients and mammalian animal models is non-trivial. In this review we briefly illustrate the state of the art of epilepsy research in zebrafish with particular focus on calcium imaging of epileptic seizures in the larval zebrafish. We illustrate the utility of a dynamic systems perspective on the epileptic brain for providing a principled approach to linking observations across species and identifying those features of brain dynamics that are most relevant to epilepsy. In the following section we survey the literature for imaging features associated with epilepsy and epileptic seizures and link these to observations made from humans and other more traditional animal models. We conclude by identifying the key challenges still facing epilepsy research in the larval zebrafish and indicate strategies for future research to address these and integrate more directly with the themes and questions that emerge from investigating epilepsy in other model systems and human patients.

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We conclude that TBC1269 administered before allergen challenge as a single intravenous dose does not attenuate early or late asthmatic responses to allergen in asthmatic subjects.