Simvastatin-Ezetimibe enhances growth factor expression and attenuates neuron loss in the hippocampus in a model of intracerebral hemorrhage.

Abstract

Intracerebral hemorrhage (ICH) is a common and severe neurological disorder associated with high morbidity and mortality rates. Despite extensive research into its pathology, there are no clinically approved neuroprotective treatments for ICH. Increasing evidence has revealed that inflammatory responses mediate the pathophysiological processes of brain injury following ICH. Experimental ICH was induced by direct infusion of 100 μL fresh (non-heparinized) autologous whole blood into the right basal ganglia of Sprague-Dawley rats at a constant rate (10 μL/min). The simvastatin group was administered simvastatin (15 mg/kg) and the combination therapy group was administered simvastatin (10 mg/kg) and ezetimibe (10 mg/kg). Magnetic resonance imaging (MRI), the forelimb use asymmetry test, the Morris water maze test, and two biomarkers were used to evaluate the effect of simvastatin and combination therapy. MRI imaging revealed that combination therapy resulted in significantly reduced perihematomal edema. Biomarker analyses revealed that both treatments led to significantly reduced endothelial inflammatory responses. The forelimb use asymmetry test revealed that both treatment groups had significantly improved neurological outcomes. The Morris water maze test revealed improved neurological function after combined therapy, which also led to less neuronal loss in the hippocampal CA1 region. In conclusion, simvastatin-ezetimibe combination therapy can improve neurological function, attenuate the endothelial inflammatory response and lead to less neuronal loss in the hippocampal CA1 region in a rat model of ICH.

• Authors: Kuo-Wei Wang, Cheng-Loong Liang, Lee-Ren Yeh, Kuo-Ying Liu, Chao-Chi Chen, Jui-Sheng Chen, Han-Jung Chen, Hao-Kuang Wang
• Journal: Fundamental & clinical pharmacology (Fundam Clin Pharmacol) Vol. 35 Issue 4 Pg. 634-644 (Aug 2021) ISSN: 1472-8206 [Electronic] England
• PMID: 33278834 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.

Chemical References

• Intercellular Signaling Peptides and Proteins
• Neuroprotective Agents
• Simvastatin
• Ezetimibe

Topics

• Animals
• Cerebral Hemorrhage (drug therapy, metabolism)
• Disease Models, Animal
• Drug Therapy, Combination
• Ezetimibe (pharmacology, therapeutic use)
• Hippocampus (metabolism)
• Intercellular Signaling Peptides and Proteins (metabolism)
• Male
• Maze Learning
• Neurons (drug effects)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Simvastatin (pharmacology, therapeutic use)