Xiao Ran1, Jing Xiang2, Pan-Pan Song3, Li Jiang4, Ben-Ke Liu5, Yue Hu6. 1. Department of Neurology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, China; Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, China. Electronic address: 1136840185@qq.com. 2. MEG Center, Department of Neurology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45220, USA. Electronic address: jing.xiang@cchmc.org. 3. Department of Neurology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, China; Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, China. Electronic address: 1336971688@qq.com. 4. Department of Neurology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, China; Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, China. Electronic address: jiangli19640718@163.com. 5. Department of Neurology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, China; Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, China. Electronic address: 506118975@qq.com. 6. Department of Neurology, Children's Hospital of Chongqing Medical University, China; Ministry of Education Key Laboratory of Child Development and Disorders, China; Key Laboratory of Pediatrics in Chongqing, CSTC2009CA5002, China; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, China. Electronic address: huyue915@163.com.
Abstract
OBJECTIVE: To assess the dynamic changes in the average and peak spectral power of fast ripples (FRs) in the hippocampi after interventions with valproate sodium (VPA), carbenoxolone (CBX) and quinine (QUIN). METHOD: Adult rats were used to establish a lithium-pilocarpine (pilo) epileptic model, and were assigned to a lithium-pilocarpine (PILO), VPA + PILO, QUIN + PILO or CBX + PILO group. Intracranial electroencephalography was performed before and after status epilepticus (SE). The hippocampal connexin (CX) 43, CX32 and CX36 expressions were analyzed via western blotting. RESULTS: The time required for the disappearance of SE after chloral hydrate injection was lower in the intervention groups than in the PILO group (p < 0.05). Seizures induced CX43 expression, but had no significant effects on CX36 or CX32 expressions. Pretreatment with VPA, QUIN and CBX inhibited CX43, CX36 and CX32 expression after SE. The average spectral power of the FRs was significantly lower in the VPA + PILO and QUIN + PILO groups than in the PILO group at 10 min after SE, 10 min before chloral hydrate injection, and 10 min after chloral hydrate injection (p < 0.05). The average spectral power of FRs was lower in the CBX + PILO group than in the PILO group at 10 min after SE (p < 0.05). The average spectral power of FRs in the 3 intervention groups recovered to the baseline level at 10 min after chloral hydrate injection and persisted for 3 days after SE. The dynamic changes in the average and peak spectral power of FRs were similar. SIGNIFICANCE: After SE, CX may participate in pathological FR generation by establishing abnormal electrical synaptic transmission. Gap junction blockers can inhibit various CX expressions, and thus decrease FR energy and alleviate the degree of seizure. These findings could contribute to the development of new anti-epileptic drugs with novel mechanistic targets.
OBJECTIVE: To assess the dynamic changes in the average and peak spectral power of fast ripples (FRs) in the hippocampi after interventions with valproate sodium (VPA), carbenoxolone (CBX) and quinine (QUIN). METHOD: Adult rats were used to establish a lithium-pilocarpine (pilo) epileptic model, and were assigned to a lithium-pilocarpine (PILO), VPA + PILO, QUIN + PILO or CBX + PILO group. Intracranial electroencephalography was performed before and after status epilepticus (SE). The hippocampal connexin (CX) 43, CX32 and CX36 expressions were analyzed via western blotting. RESULTS: The time required for the disappearance of SE after chloral hydrate injection was lower in the intervention groups than in the PILO group (p < 0.05). Seizures induced CX43 expression, but had no significant effects on CX36 or CX32 expressions. Pretreatment with VPA, QUIN and CBX inhibited CX43, CX36 and CX32 expression after SE. The average spectral power of the FRs was significantly lower in the VPA + PILO and QUIN + PILO groups than in the PILO group at 10 min after SE, 10 min before chloral hydrate injection, and 10 min after chloral hydrate injection (p < 0.05). The average spectral power of FRs was lower in the CBX + PILO group than in the PILO group at 10 min after SE (p < 0.05). The average spectral power of FRs in the 3 intervention groups recovered to the baseline level at 10 min after chloral hydrate injection and persisted for 3 days after SE. The dynamic changes in the average and peak spectral power of FRs were similar. SIGNIFICANCE: After SE, CX may participate in pathological FR generation by establishing abnormal electrical synaptic transmission. Gap junction blockers can inhibit various CX expressions, and thus decrease FR energy and alleviate the degree of seizure. These findings could contribute to the development of new anti-epileptic drugs with novel mechanistic targets.
Authors: Laura Medina-Ceja; Juan C Salazar-Sánchez; Jorge Ortega-Ibarra; Alberto Morales-Villagrán Journal: Int J Mol Sci Date: 2019-11-27 Impact factor: 5.923
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