Blood-brain barrier dysfunction in hemorrhagic transformation: a therapeutic opportunity for nanoparticles and melatonin

Abstract

Stroke is the second leading cause of death worldwide, estimated that 1/6 of the world population will suffer it once in their life. The most common type of this medical condition is the ischemic stroke (IS), produced by a thrombotic or embolic occlusion of a major cerebral artery or its branches, leading to the formation of a complex infarct region caused by oxidative stress, excitotoxicity and endothelial dysfunction. Nowadays, the immediate treatment for IS involves thrombolytic agents or mechanical thrombectomy, depending on the integrity of the blood-brain barrier (BBB). A common stroke complication is the hemorrhagic transformation (HT), which consists of bleeding into the ischemic brain area. Currently, better treatments for IS are urgently needed. As such, the neurohormone melatonin has been proposed as a good candidate due to its antioxidant, anti-inflammatory and neuroprotective effects, particularly against lipid peroxidation and oxidative stress during brain ischemia. Here, we proposed to develop intravenous or intranasal melatonin nanoformulation to specifically target the brain in stroke patients. Nowadays, the challenge is to find a formulation able to cross the barriers and reach the target organ in an effective dose to generate the pharmacological effect. In this review, we discuss the current literature about stroke pathophysiology, melatonin properties and its potential use in nanoformulations as a novel therapeutic approach for ischemic stroke.

Lactate Dehydrogenase Predicts Hemorrhagic Transformation in Patients with Acute Ischemic Stroke

“…Cell death is usually accompanied by cytoplasmic destruction, which releases LDH into the peripheral circulation [19]. HT patients often have more severe pathological destruction than non-HT patients, with more cell necrosis and theoretically higher peripheral LDH release than non-HT patients [20,21]. A recent study reported that elevated serum LDH levels could predict unfavorable outcomes following recombinant tissue plasminogen activator thrombolysis in patients with AIS [22].…”