TY - JOUR T1 - Ropivacaine Protects against Memory Impairment and Hippocampal Damage in a Rat Neurodegeneration Model. AU - Chiu,Kuan-Ming, AU - Lin,Tzu-Yu, AU - Lee,Ming-Yi, AU - Lu,Cheng-Wei, AU - Wang,Ming-Jiuh, AU - Wang,Su-Jane, Y1 - 2018/09/26/ PY - 2018/06/22/received PY - 2018/08/21/accepted PY - 2018/9/27/pubmed PY - 2018/12/20/medline PY - 2018/9/27/entrez KW - Excitotoxicity KW - Glutamate KW - Kainic acid KW - Neuroprotection KW - Ropivacaine SP - 307 EP - 315 JF - Pharmacology JO - Pharmacology VL - 102 IS - 5-6 N2 - BACKGROUND: Ropivacaine, a long-acting amide local anesthetic agent, has been demonstrated to inhibit glutamatergic transmission. Glutamate neurotoxicity plays a pivotal role in the pathogenesis of brain disorders. The purpose of this study is to investigate the neuroprotective effect of ropivacaine against brain damage induced by kainic acid (KA), an analogue of glutamate. METHODS: Rats were injected with ropivacaine (0.4 or 2 mg/kg, intraperitoneal) 30 min before KA treatment (15 mg/kg, intraperitoneal). KA-induced memory impairment was evaluated using the Morris water maze test. Extracellular hippocampal glutamate levels were assessed using high-performance liquid chromatography. Neuronal death was verified using Fluoro-Jade B and neutral red staining, and apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Western blotting was conducted to assay the levels of activated (cleaved) caspase-3 and the phosphorylation of different mitogen-activated protein kinases (MAPKs). -Results: Ropivacaine pretreatment effectively prevented KA-induced memory impairment. KA-induced elevations of -glutamate release in rat hippocampi were inhibited by pretreatment with ropivacaine. Histopathological and TUNEL staining analyzes showed that ropivacaine inhibited KA-induced neuronal death and apoptosis in the hippocampal CA3 region. KA-induced caspase-3 activation and MAPKs phosphorylation in the hippocampus were also reduced by ropivacaine pretreatment. CONCLUSIONS: This study -demonstrates that ropivacaine executes a protective action against KA-induced neuronal damage and apoptosis in vivo. Protective effects may be caused by glutamate level reduction, caspase-3 activation suppression, and MAPKs phosphorylation reduction. Our findings indicate that ropivacaine can benefit prevention or treatment of glutamate excitotoxicity-related neurodegenerative diseases. SN - 1423-0313 UR - https://www.unboundmedicine.com/medline/citation/30257255/Ropivacaine_Protects_against_Memory_Impairment_and_Hippocampal_Damage_in_a_Rat_Neurodegeneration_Model_ DB - PRIME DP - Unbound Medicine ER -