Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.
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PMID:Pravastatin acute neuroprotective effects depend on blood brain barrier integrity in experimental cerebral ischemia. 2591 35

Statins, drugs known for lipid lowering capabilities and reduction of cardiovascular disease, have demonstrated neuroprotective effects following ischemic stroke in retrospective clinical and animal studies. However, dosing (methods, time, type of statin, and quantity) varies across studies, limiting the clinical applicability of these findings. Furthermore, a comprehensive review of statins in edema and blood-brain barrier (BBB) breakdown is needed to provide insight on diverse, less explored neuroprotective effects. In the present study, we conduct a meta-analysis of publications evaluating statin administration in animal models of ischemic stroke. We review statins' most effective dosing regimen in four outcomes-infarct, edema, BBB breakdown, and functional outcome-to characterize several parameters of benefit associated with statin administration. A search term was constructed to identify experimental murine studies exploring statin use after transient middle cerebral artery occlusion (tMCAO) in PubMed, Web of Science, and Embase. Extracted data included statin type, dose, time and method of administration, and the four predetermined outcomes (functional outcome, edema, BBB breakdown, and infarction). A meta-analysis and stratified meta-regression were conducted using the standardized mean difference (SMD) method for continuous measurements. Included publications were assessed for bias using SYRCLE's RoB tool for animal studies. A total of 24 studies were included. Statin administration significantly reduced infarct volume (p < 0.0001), edema volume (p < 0.002), and neurological deficit (p < 0.0001). Simvastatin and pravastatin were most effective in reducing infarct volume when compared with atorvastatin (p = 0.0475, p = 0.0004) and rosuvastatin (p = 0.0036, p < 0.0001). Pravastatin outperformed all others in functional outcome. Subcutaneous (SC) injection was most effective in all outcomes. Statin therapy reduced BBB breakdown according to our systematic review. Mean study quality was 4.6/10. While statin therapy evidently improves neurological outcome following ischemic stroke, this analysis adds to our understanding of dosing and statins' effects on edema and BBB breakdown. These findings will aid the design of future studies investigating statin use and have larger implications for the clinical care of ischemic stroke patients.
Transl Stroke Res 2020 08
PMID:Statin Therapy in Ischemic Stroke Models: A Meta-Analysis. 3178 61


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