The Effects of Atorvastatin on Global Cerebral Ischemia-Induced Neuronal Death.
A Ra KhoDae Ki HongBeom Seok KangWoo-Jung ParkKyung Chan ChoiKyoung-Ha ParkSang Won SuhPublished in: International journal of molecular sciences (2021)
(1) Background and Purpose: Global cerebral ischemia-induced severe hypoxic brain damage is one of the main causes of mortality and long-term neurologic disability even after receiving early blood reperfusion. This study aimed to test the hypothesis that atorvastatin potentially has neuroprotective effects in global cerebral ischemia (GCI). (2) Methods: We performed two sets of experiments, analyzing acute (1-week) and chronic (4-week) treatments. For the vehicle (Veh) and statin treatments, 1 mL of 0.9% saline and 5 mg/kg of atorvastatin (ATOR) were administered orally. For histological analysis, we used the following staining protocols: Fluoro-Jade B and NeuN, 4-hydroxynonenal, CD11b and GFAP, IgG, SMI71, and vWF. Finally, we evaluated the cognitive function with a battery of behavioral tests. (3) Results: The GCI-ATOR group showed significantly reduced neuronal death, oxidative stress, inflammation, and BBB disruption compared with the GCI-Veh group. Moreover, the GCI-ATOR group showed decreased endothelial damage and VV proliferation and had significantly improved cognitive function compared with the GCI-Veh group in both models. (4) Conclusions: ATOR has neuroprotective effects and helps recover the cognitive function after GCI in rats. Therefore, administration of atorvastatin may be a therapeutic option in managing GCI after CA.
Keyphrases
- cerebral ischemia
- oxidative stress
- blood brain barrier
- subarachnoid hemorrhage
- diabetic rats
- brain injury
- drug induced
- high glucose
- type diabetes
- endothelial cells
- multiple sclerosis
- randomized controlled trial
- computed tomography
- cardiovascular disease
- induced apoptosis
- cardiovascular events
- coronary artery disease
- early onset
- dna damage
- clinical trial
- heart failure
- left ventricular
- white matter
- acute myocardial infarction
- endoplasmic reticulum stress
- resting state
- functional connectivity