The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

  • Jin, Zhen (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Jung, Yohan (Department of Neurology, Changwon Fatima Hospital) ;
  • Yi, Chin-ok (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Lee, Jong Youl (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Jeong, Eun Ae (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Lee, Jung Eun (Department of Thoracic and Cardiovascular Surgery, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Park, Ki-Jong (Department of Neurology, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Kwon, Oh-Young (Department of Neurology, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Lim, Byeong Hoon (Department of Neurology, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Choi, Nack-Cheon (Department of Neurology, Institute of Health Sciences, College of Medicine, Gyeongsang National University) ;
  • Roh, Gu Seob (Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University)
  • Received : 2017.11.07
  • Accepted : 2018.02.07
  • Published : 2018.05.01
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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.

Keywords

References

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