In search of new therapeutic strategies for the treatment of hypoxia-ischemia-induced brain damages

Abstract

In post stroke patients, high mortality and low percentage of cure is connected with defficiency of chemicals exhibiting wide therapeutic windows and acting on complex processes accompanying ischemia and reperfusion. In clinical trials related to the treatment of stroke are e.g. thrombolytic compounds, chemicals lowering blood pressure and substances having properties of calcium channel antagonists as well as antagonists of histamine and glutamate receptors. A lot of efforts are focusing on clinical use of transcranial laser therapy utilizing infrared light (808 nm) for stimulation of blood flow in brain vessels. Moreover, there are intensive experimental studies wich are based on the cellular and animal models of stroke. In these studies, searching for new therapies involves stem cells, stimulation of angiogenesis and neurogenesis, inhibition of excitotoxicity, oxidative stress and inflammation, developing the resistance and tolerance to stroke by conditioning as well as testing new chemicals having neuroprotective properties. Recently, we have demonstrated that raloxifene and diindolylmethane are promising tools to protect neurons against hypoxic damage. Their neuroprotective effects refer to inhibition of apoptosis, activation of the estrogen receptor ERα and an impairment of the aryl hydrocarbon receptor (AhR) signaling pathways. We postulate, that the future treatment of stroke can provide the synergistic neuroprotective effect via combination of chemicals exhibiting various mechanisms of action and connecting rational pharmacotherapy with other therapeutic strategies such as hypothermia or trombectomy.