Ischemic stroke is a major cause of death and long-term disability worldwide, associated with significant clinical and socioeconomical implications. Thrombolisis by systemic administration of rtPA is currently the only approved therapy that can be used in fewer than 10% of ischemic strokes due to its limited therapeutic window. During the last decades, numerous neuroprotective strategies, aimed at targeting the acute detrimental mechanisms leading to a rapid cell demise in the ischemic core regions, have led to disappointing results in clinical trials because of lack of efficacy or unacceptable side-effect.
More recently, immunomodulation has been suggested as a promising therapeutic approach. Indeed, the evolution of ischemic tissue damage is strongly affected by an immune reaction that involves soluble mediators, such as cytokines and chemokines, and specialised cells activated locally or recruited from the periphery. The immune system is implicated in all stages of the ischemic cascade, from the acute intravascular reaction due to blood flow disruption, to the development of brain tissue damage, repair and regeneration. A better understanding of the spatio-temporal evolution of the immune response in relation to the ischemic event, as well as its potential role in the late repair and regeneration processes is crucial for the development of novel effective therapeutics.
Translational research for the development of novel stroke therapeutics is the mission of the “Basic and Translational Stroke Research Unit” coordinated by Dr Diana Amantea at the University of Calabria.
From the injured brain to the molecular and cellular aspects of the immune system, our aim is to understand the complex interactions between the central and peripheral immune responses to stroke injury and the development of ischemic neuronal damage.
During the last 15 years the activity of our research group has significantly improved the understanding of crucial cellular and molecular events involved in stroke pathophysiology. These include the characterization of local inflammatory responses mediated by MMPs, IL-1beta and RAGE; the involvement of the endocannabinoid system and the role of transcription factors (e.g, STAT3) and of oxidative stress (e.g., H2O2, catalase) in the development of brain damage. Moreover, the neuroprotective properties of a series of compounds including MMPs-inhibitors, natural products (Bergamot essential oil), hormones (17beta-estradiol, leptin) and NO modulators have been characterised.
Recent findings from our laboratory demonstrate that pharmacological modulation of the systemic inflammatory response, consisting in potentiating the contribution of beneficial M2 macrophages while reducing the brain infiltration of detrimental neutrophils, may provide extraordinary neuroprotection in ischemic stroke models. The efficacy of pharmacological manipulation of such responses has recently been patented.
Technological transfer activity of the research unit is reflected in the recently created spin-off SNAR&D (Services to Neurotherapeutics Advancement, Research & Development) coordinated by Dr Diana Amantea with the participation of young researchers and clinicians with renowned experience in the field of neurotherapeutics R&D.
The unit operates within the framework of the ISO basic science and of the Stroke Centre and Emergency Trust (SCENT) an integrated research centre aimed at gathering and coordinating a number of clinical and research institutions working in the field of stroke and other emergency/urgency neurological conditions. The common aim is to facilitate the integration between qualified professionals and technological resources to improve the treatment of stroke patients.