Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage

Zhu, Xinjian; Dong, Jun; Han, Bing; Huang, Rongrong; Zhang, Aifeng; Xia, Zhengrong; Chang, He; Chao, Jie; Yao, Honghong

doi:10.3389/fncel.2017.00377

Cited by 83 publications

(43 citation statements)

References 47 publications

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“…22 For instance over generation of superoxide anion in the hippocampus of kindled mice by PTZ was reported. 5 In another example, thiol groups including glutathione (GSH) and glutathione disulfide (GSSG) decreased in the cerebral cortex of mice when they were kindled by PTZ. 23 Researchers also reported that enhanced level of intracellular Ca 2+ as a result from activation of inotropic glutamate receptors during abnormal neuronal excitations leads to uncontrolled production of reactive oxygen species (ROS).…”

Section: Discussionmentioning

confidence: 99%

“…4 In addition, seizures followed by PTZ administration have been propounded as an important cause of oxidative status imbalance in some brain areas including hippocampus. 5 For example, PTZ infusion associated with the sever stimulation of N-Methyl-Daspartate (NMDA) receptors has been shown to elevate the level of free radicals such as nitric oxide (NO) and peroxynitrite in the brain of rats. 6 On the other hand, the antioxidant properties of angiotensin-converting enzyme (ACE) inhibitors have been accepted.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

et al. 2019

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IntroductionEpileptic seizures are considered as a sever abnormal activity of neurons in specific areas of brain such as temporal lobe. 1 This abnormal activity of neurons can be followed by brain oxidative stress and disturbance of cognitive behaviors when they take place repeatedly. 2 In the epileptic seizure models, antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase have been also shown to protect the brain of rats against oxidative damage. 3 In large number of animal studies, pentylenetetrazole (PTZ) has been repeatedly administered for induction an epilepsy model. 1 It has been ducumented that PTZstimulated seizures was accompanied with motor activity impairment, learning and memory dysfunction, axiety and increased level of hippocampal inflammatory cytokines in rats. 4 In addition, seizures followed by PTZ administration have been propounded as an important cause of oxidative status imbalance in some brain areas including hippocampus. 5 For example, PTZ infusion associated with the sever stimulation of N-Methyl-Daspartate (NMDA) receptors has been shown to elevate the level of free radicals such as nitric oxide (NO) and peroxynitrite in the brain of rats. 6 On the other hand, the antioxidant properties of angiotensin-converting enzyme (ACE) inhibitors have been accepted. 7 Captopril as a known ACE inhibitor scavenges free radicals in various tissues. 8 Captopril has been demonstrated to reinforce enzymatic and nonenzymatic defense in different tissues. 9 Scientific evidence has indicated that captopril and valsartan (a specific AT1 receptor inhibitor) attenuate A B S T R A C TBackground: Frequent seizure is followed by overproduction of free radicals and brain oxidative stress. Renin angiotensin system (RAS) has some effects on central nervous system. We designed this research to challenge the effect of captopril as an angiotensin converting enzyme (ACE) inhibitor against brain oxidative stress in pentylenetetrazole (PTZ) -induced seizures in mice. Methods: The groups were including (1) Control (saline); (2) PTZ (100 mg/kg, i.p.), (3-5) PTZ-captopril (Capto) that received three doses of Capto 10, 50 and 100 mg/kg 30 min before PTZ injection. Latency time in the onset minimal clonic seizures (MCS) and generalized tonic-clonic seizures (GTCS) were recorded. The level of malondialdehyde (MDA) and total thiol, as well as superoxide dismutase (SOD) and catalase (CAT) activity in the hippocampus and cortex were measured. Results: All doses of captopril postponed the onset of MCS and GTCS. Accumulation of MDA in the brain tissues of PTZ group was higher than control group, while total thiol content and CAT activity were lower. Pretreatment with captopril (100 mg/kg) diminished MDA concentration compared with PTZ group. Captopril (50 and 100 mg/kg) also increased the level of total thiol groups versus PTZ group. Captopril injection (50 and 100 mg/kg) elevated the activity of SOD and CAT in the brain tissues. In addition captopril administration diminished mortality rat...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

et al. 2019

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“…[30] Zhu ve ark. [31] (2017) nöronal NOS, PTZ-kindling ile indüklenen epilepside ER stresini ve oksidatif hasarı tetikleyen bir sinyal molekülü olarak tanımlanmaya çalışmış, nöronal NOS'un hipokampal ER stresini ve oksidatif hasarı tetiklemek için reaktif azot türlerinin önemli bir üyesi olan peroksinitrit yoluyla etki ettiğini göstermiştirler. Kronik epilepsinin neden olduğu ER stres ve oksidatif hasar için özel bir mekanizma ve kronik epilepsi hastalarında potansiyel bir terapötik hedef olabileceği belirtilmiştir.…”

Section: Discussionunclassified

Effects of pentylenetetrazol-induced kindling on mature and immature rat behavior, emotional learning and levels of nitric oxide in brain and serum

Göl¹,

Erdoğan²,

Kanan³

et al. 2018

Epilepsi

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Objectives: This aim of this study was to investigate emotional memory-learning and behavioral functions, as well as the relationship between these functions and the nitric oxide (NO) level in the serum and brain of mature and immature rats following pentylenetetrazol (PTZ)-induced kindling. Methods: A total of 36 male Wistar albino rats were included in the study. Kindling was induced by repeated injections of a subconvulsive dose of PTZ (30 mg/kg) on alternate days until kindling development. The rats were tested using an elevated T-maze and an open-field test after PTZ kindling. Brain and serum NO levels were assessed. Results: Although both mature and immature rats were susceptible to PTZ-induced seizures, the mature rats had seizures of longer duration than the immature rats, with the exception of infants. There was no demonstrated effect of PTZ-kindling on emotional memory and learning functions in any of the rats. Anxiety levels were low in the mature-kindled rats but were high in the immature-kindled rats. NO levels in the brain were elevated and anxiety reactions were below normal in the mature rats. In immature rats, however, NO levels were normal, but anxiety reactions were elevated. Conclusion: Seizure susceptibility, emotional responses, and the relationship between these factors and brain NO level after PTZ-kindling differed in rats based on brain maturity status.

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“…According to the method 45 , PTZ (35 mg/kg) was administered to the mice by intraperitoneal (i.p.) injection every other day for 30 days.…”

Section: Methodsmentioning

confidence: 99%

Transgenic overexpression of furin increases epileptic susceptibility

Yang

Tian

et al. 2018

Cell Death Dis

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The proprotein convertase Furin plays crucial roles in the pathology of many diseases. However, the specific role of furin in epilepsy remains unclear. In our study, furin protein was increased in the temporal neocortex of epileptic patients and in the hippocampus and cortex of epileptic mice. The furin transgenic (TG) mice showed increased susceptibility to epilepsy and heightened epileptic activity compared with wild-type (WT) mice. Conversely, lentivirus-mediated knockdown of furin restrained epileptic activity. Using whole-cell patch clamp, furin knockdown and overexpression influenced neuronal inhibitory by regulating postsynaptic gamma-aminobutyric acid A receptor (GABAAR)-mediated synaptic transmission. Importantly, furin influenced the expression of GABAAR β2/3 membrane and total protein in epileptic mice by changing transcription level of GABAAR β2/3, not the protein degradation. These results reveal that furin may regulate GABAAR-mediated inhibitory synaptic transmission by altering the transcription of GABAAR β2/3 subunits in epilepsy; this finding could provide new insight into epilepsy prevention and treatment.

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Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling Epilepsy-Induced Hippocampal Endoplasmic Reticulum Stress and Oxidative Damage

Cited by 83 publications

References 47 publications

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

Effect of Captopril on Brain Oxidative Damage in Pentylenetetrazole-Induced Seizures in Mice<br />

Effects of pentylenetetrazol-induced kindling on mature and immature rat behavior, emotional learning and levels of nitric oxide in brain and serum

Transgenic overexpression of furin increases epileptic susceptibility

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