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Effects of erythropoietin pretreatment on single dose pentylentetrazole-induced seizures in rats.
Biotechnic & Histochemistry ( IF 1.6 ) Pub Date : 2020-01-31 , DOI: 10.1080/10520295.2020.1713398
Ayşegul Kapucu 1 , Gülay Üzüm 2 , Zülal Kaptan 3 , Kadriye Akgün-Dar 1
Affiliation  

Although it is accepted that prolonged and repeated seizures can cause epileptogenesis, memory deficits and neuronal death, the precise relation between epileptic seizures and neuronal death remains unclear. Erythropoietin (EPO) exhibits neuroprotective and anti-epileptic effects. We investigated the effect of a single pentylentetrazole (PTZ) induced tonic-clonic seizure on the pyramidal neurons of the cornu ammonis 1 (CA1) and CA3 regions of hippocampus. We also investigated the effects of EPO on seizure, memory and on brain-derived neurotrophic factor (BDNF), tyrosine receptor kinase-B, sirtuin-1 (SIRT1), which are important for memory. Forty male rats were divided into four groups: control, saline treated, single 60 mg/kg dose PTZ treated, 3000 IU/kg EPO treated, and 3000 IU/kg EPO treated 24 h before PTZ administration. Seizure latency and severity were assessed following PTZ injection. A passive avoidance test was performed 24 h after seizure. BDNF, TrkB and SIRT1 levels were measured in serum, hippocampus and cortex. The hippocampus was examined histologically, and neuronal nuclear antigen (NeuN) was investigated using immunohistochemistry. EPO pretreatment decreased seizure severity and prolonged seizure latency. Single dose PTZ-induced seizures did not affect memory. Numbers of cells in the CA1 region did not change, although the number of dark stained neuron increased. Both total cell numbers and percentage of dark stained cells were elevated in the CA3 region following PTZ induced seizures. EPO pretreatment decreased the number of dark cells in both CA1 and CA3 regions and the number of cells in the CA3 region. NeuN labeling was unchanged in the CA1 and CA3 regions in the PTZ group; however, EPO pretreatment increased NeuN labeling in the CA3 region. Although EPO exhibited an anticonvulsive effect, single dose EPO pretreatment did not affect memory in either animals not exposed to PTZ or animals that had been subjected to PTZ-induced seizures. EPO pretreatment prolonged seizure latency and reduced seizure severity after PTZ-induced seizures. The anti-seizure and neuroprotective effects of EPO pretreatment may be due to the protection of CA1 and CA3 neurons, possibly owing to SIRT1 and BDNF activity.



中文翻译:

促红细胞生成素预处理对单次戊喷噻唑诱导的大鼠癫痫发作的影响。

尽管长期和反复发作可能会引起癫痫发作,记忆力减退和神经元死亡,但癫痫发作与神经元死亡之间的确切关系仍不清楚。促红细胞生成素(EPO)具有神经保护和抗癫痫作用。我们调查了单个戊戊四唑(PTZ)引起的强直阵挛性癫痫发作对海马角膜1(CA1)和CA3区域的锥体神经元的影响。我们还研究了EPO对癫痫发作,记忆力以及脑源性神经营养因子(BDNF),酪氨酸受体激酶B,sirtuin-1(SIRT1)的影响,这些作用对于记忆力很重要。将四十只雄性大鼠分为四组:对照组,生理盐水处理,单剂量60 mg / kg剂量的PTZ处理,3000 IU / kg EPO处理和3000 IU / kg EPO处理。注射PTZ后评估癫痫潜伏期和严重程度。癫痫发作24小时后进行被动回避测试。在血清,海马和皮质中测量BDNF,TrkB和SIRT1水平。组织学检查海马,并使用免疫组织化学研究神经元核抗原(NeuN)。EPO预处理可降低癫痫发作的严重程度并延长癫痫发作潜伏期。单剂量PTZ诱发的癫痫发作不影响记忆。尽管深色神经元的数量增加了,但CA1区的细胞数量没有变化。PTZ诱发癫痫发作后,CA3区的总细胞数和深色细胞的百分比均升高。EPO预处理减少了CA1和CA3区域中暗细胞的数量以及CA3区域中暗细胞的数量。在PTZ组的CA1和CA3区,NeuN标记未改变;然而,EPO预处理增加了CA3区的NeuN标记。尽管EPO表现出抗惊厥作用,但单剂量EPO预处理不会影响未暴露于PTZ的动物或已遭受PTZ诱发的癫痫发作的动物的记忆。EPO预处理可延长癫痫发作潜伏期并降低PTZ诱发的癫痫发作后的癫痫发作严重程度。EPO预处理的抗癫痫发作和神经保护作用可能是由于对CA1和CA3神经元的保护,可能是由于SIRT1和BDNF活性。单剂量EPO预处理不会影响未暴露于PTZ的动物或已遭受PTZ诱发的癫痫发作的动物的记忆。EPO预处理可延长癫痫发作潜伏期,并降低PTZ诱发的癫痫发作后的癫痫发作严重程度。EPO预处理的抗癫痫发作和神经保护作用可能是由于对CA1和CA3神经元的保护,可能是由于SIRT1和BDNF活性。单剂量EPO预处理不会影响未暴露于PTZ的动物或已遭受PTZ诱发的癫痫发作的动物的记忆。EPO预处理可延长癫痫发作潜伏期,并降低PTZ诱发的癫痫发作后的癫痫发作严重程度。EPO预处理的抗癫痫发作和神经保护作用可能是由于对CA1和CA3神经元的保护,可能是由于SIRT1和BDNF活性。

更新日期:2020-01-31
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