Tacrolimus (FK506) and cyclosporin A (CsA) are immunosuppressants that have well-known neuroprotective actions. However, the drugs also have numerous negative neurological side effects observed in clinical practice. The problem of the long-term consequences of the immunosuppressive treatment has never been explored experimentally. Therefore, we focused on the FK506 and CsA influence on the deve...

traumatic brain injury (tbi) is one of the most common neurological diseases with no definite treatment. erythropoietin (epo) and progesterone (prog) have been shown to have neuroprotective effects in different types of experimental brain injury models. this study was designed to determine the effect of epo, prog and combination of epo/prog on neurological outcome after traumatic brain injury. ...

Pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and peptide histidine-isoleucine (PHI), are structurally related endogenous peptides widely expressed in the central and peripheral nervous system and showing rich profile of biological activities. They act as neurotransmitters, neuromodulators and neurotrophic factors. Recently, their neuroprotectiv...

For decades, the overwhelming emphasis on the development of therapeutic interventions for the treatment of stroke has been in the area of neuroprotection, acute intervention to reduce the volume of cerebral infarction, and the sequellae of secondary cell death, whether by necrosis or apoptosis. Concerted efforts to elucidate mechanisms of cell death were translated into the development of many...

The general failure of neuroprotectants in clinical trials of ischemic stroke points to the possibility of a fundamental blind spot in the current conception of ischemic brain injury, the "ischemic cascade". This is the fourth in a series of four papers whose purpose is to work towards a revision of the concept of brain ischemia by applying network concepts to develop a bistable model of brain ...

In this issue, Bath et al. use state of the art meta-analytical tools to address the pressing question of why NXY-059, a compound at the time considered to fulfil all the recommendations for the evaluation of preclinical data regarding neuroprotective drugs, has failed clinically. They demonstrate quantitatively that a negative publication bias existed, that the compound was indeed neuroprotect...

The effects of riluzole, a neuroprotective drug, on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium channels in rat dorsal root ganglion neurons were studied using the whole-cell patch clamp technique. At the resting potential, riluzole preferentially blocked TTX-S sodium channels, whereas at more negative potentials, it blocked both types of sodium channels almost equa...

There have been numerous failures in the field of acute stroke therapy over many years, but the first large clinical trial showing preliminary indications of efficacy and safety of a neuroprotective drug, NXY-059, has now been fully reported. If confirmed, it will mean that a second therapy for acute stroke has been identified and neuroprotective drug development as a class can proceed. Additio...

BACKGROUND AND PURPOSE The advent of controlled clinical trials revolutionized clinical medicine over the course of the 20th century. The objective of this study was to quantitatively characterize developments in clinical trial methodology over time in the field of acute ischemic stroke. METHODS All controlled trials targeting acute ischemic stroke with a final report in English were identifi...

The neutral results of the SAINT II study1 dashed the hopes for a second ischemic stroke drug in the near future. Although this is certainly disappointing for stroke neurologists, a careful analysis of the NXY-059 development program reveals several deficiencies, which if properly addressed, might revitalize and strengthen the field of neuroprotection for acute ischemic stroke. This critique po...