Feasibility and safety of erythropoietin for neuroprotection after perinatal arterial ischemic stroke

Objective To perform a feasibility and safety study with recombinant human erythropoietin (rhEPO) in neonates with perinatal arterial ischemic stroke. Study design Neonates with a magnetic resonance imaging-confirmed perinatal arterial ischemic stroke (n = 21) were treated with 1000 IU/kg rhEPO immediately after diagnosis and at 24 and 48 hours after the first dose. Repeat magnetic resonance imaging was performed when the patients were 3 months of age. Coagulation and hematologic variables (red blood cells, white blood cells, platelet counts) were performed in the first week after initiation of treatment. We also compared 10 patients who were treated with rhEPO with 10 historic infants with perinatal arterial ischemic stroke matched for the involved arterial branch to investigate whether rhEPO reduces the residual size of the infarction and subsequent brain growth between first and second scan. Results Seizures were a first symptom in 20 of 21 neonates. Heart rate, blood pressure, and coagulation function were in the normal range, as were red blood cells, white blood cells, and platelet counts. In a subgroup of 10 rhEPO-treated neonates, no differences were detected in residual infarction volumes or neurodevelopmental outcome compared with their historical nontreated counterparts. Conclusions rhEPO in neonates with perinatal arterial ischemic stroke had no adverse effects on red blood cells, white blood cells, platelets counts, or coagulation. rhEPO, 3000 IU/kg in total, given during a 3-day period, appears to be a safe therapy. The beneficial effects remains to be demonstrated in a larger, randomized, double-blind, placebo-controlled trial. © 2014 Mosby Inc

Pharmacological modulation of vascular ageing: a review from VascAgeNet

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation

Pharmacological modulation of vascular ageing : a review from VascAgeNet

Abstract: Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation