The high medical and socio-economic importance of stroke is a well-known fact. As stroke is still second cause of death and disability in the world, in spite of the clear improvement of treatment modalities, additional treatment strategies for this condition remain challenging [1]. Neuroprotection as an add-on therapy in stroke is a promising idea, and the number of studies investigating possible neuroprotective agents or methods is rising [2]. Due to variety of the neuronal death mechanisms following the disruption of the blood supply, the possible therapeutic approaches should vary as well. Most important mechanisms of brain tissue damage are neuronal excitotoxicity, peri-infarct depolarizations, local and distant inflammation, cellular apoptosis, and oxidative stress [2, 3, 4, 5]. Furthermore, it is proven that free radical oxygen species (ROS) as well as calcium play an important role in increasing the inflammatory response by raising the levels of inflammatory cytokines and endothelial cell-adhesion molecules [2, 3, 6, 7]. Development of cerebral edema, a reaction to brain tissue damage, should not be forgotten as an additional factor influencing the final extension of neuronal cell loss as well [8].

Recanalization strategies opened a new era in stroke treatment. However, as a well-known fact in clinical settings, even complete recanalization in due time does not guarantee reperfusion. Futile recanalization is a disappointing clinical condition leading to extensive brain tissue damage despite opened blood vessels. Furthermore, a complication known as reperfusion injury clearly affects the outcome in some patients [9]. Neuroprotection might be a possible treatment modality that can influence the damage to distant brain tissue in stroke. As certain types of reperfusion injury include neuroinflammation and brain edema, agents that can affect those mechanism could be of clinical benefit as well. Combining recanalization techniques with neuroprotection remains an attractive idea. Over 1000 neuroprotective agents and methods have been tested in preclinical studies, showing promising results [2, 10]. Unfortunately, more than 200 studies involving clinical trials did not provide the same results so far, and only a few have showed some clinical success [2, 4, 10].

Despite this, neuroprotective agents and non-pharmacological neuroprotective strategies (like hypothermia or transcranial direct-current stimulation) should be encouraged as a comprehensive approach to stroke treatment. Ongoing and future research focusing especially on the “add-on” approach of neuroprotection after recanalization treatment modalities may add some new insights and prove the efficacy of neuroprotection in stroke. The goals of neuroprotective agents in current studies are to reduce infarct volume and to reduce the rate of haemorrhagic transformation in ishemic stroke. An interesting approach is also to affect stroke risk, like the changing of plaque characteristics in carotid artery disease. Improving the functional outcome in stroke survivors using add-on therapy with preclinicaly proven neuroprotective potential is a final goal of all ongoing trials. In order to support this approach, the aim of this special issue of the Journal of Integrative Neuroscience is to reflect some of the newest results in the scientific field of neuroprotection in stroke.