Korean J Physiol Pharmacol.  2018 May;22(3):301-309. 10.4196/kjpp.2018.22.3.301.

Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

Affiliations
  • 1Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. anaroh@gnu.ac.kr
  • 2Department of Neurology, Changwon Fatima Hospital, Changwon 51394, Korea.
  • 3Department of Thoracic and Cardiovascular Surgery, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea.
  • 4Department of Neurology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea. ncchoi@nate.com

Abstract

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

Keyword

Atorvastatin; Hippocampal cell death; Kainic acid; Lipocalin-2; Seizures
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