Effects of Huazhuo Jiedu Shugan Decoction on Cognitive and Emotional Disorders in a Rat Model of Epilepsy: Possible Involvement of AC-cAMP-CREB Signaling and NPY Expression

Abstract

Background. Huazhuo Jiedu Shugan decoction (HJSD), a traditional Chinese medicine (TCM), has been used to treat epileptic seizures for many years. Some ingredients in these herbs have been demonstrated to be effective for the treatment of brain damage caused by epilepsy. Aim of the Study. The object of the study is to determine the effects of HJSD on cognitive and emotional disorders in a rat model of epilepsy. Materials and Methods. After a predetermined time period, rats were intraperitoneally injected with pentylenetetrazol and observed in different phases of convulsions. The cognitive and emotional changes in the epileptic rats were assessed using behavioral and immunohistochemical tests. Results. Compared with the epilepsy group, the seizure grade was reduced and seizure latency was prolonged following HJSD-H treatment (P<0.01). Compared with the control group, the epilepsy group displayed marked worse performance on the animal behavior tests (P<0.05) and the HJSD-H group displayed improved behavioral performance (P<0.05). After HJSD-H treatment, the expression of adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP), cAMP-response element binding protein (CREB), and neuropeptide Y (NPY) immunoreactive cells markedly increased in the hippocampus, compared with that of the epilepsy group (P<0.05). Conclusions. The current results demonstrate that HJSD treatment in epileptic rats markedly inhibits epileptic seizures and improves cognitive and emotional disorders, which may be related to the regulation of AC-cAMP-CREB signaling and NPY expression in the hippocampus. The effects of the HJSD treatment may provide a foundation for the use of HJSD as a prescription medicinal herb in the TCM for the treatment of epilepsy.

Influence of Different Antiepileptic Drugs on Blood Ammonia and Homocysteine Levels in Children with Epilepsy

“…[ 4 , 5 ]. In addition, cognitive impairment is also a common accompanying symptom in patients with epilepsy, with an incidence of 30–40% [ 6 , 7 ]. And, it is reported that when the blood ammonia level is significantly increased, it can also cause a significant decline in the patient's cognitive function and its serum content is positively correlated with the slow wave/fast wave ratio of each brain area of the patient [ 8 , 9 ].…”

Maternal Separation Followed by Chronic Mild Stress in Adulthood Is Associated with Concerted Epigenetic Regulation of AP-1 Complex Genes

“…It is therefore noteworthy that Npy was significantly upregulated in our models, in a pattern similar to that of CREB ( Figure 3 b). CREB has been shown to regulate Npy gene expression in the amygdala [ 23 ] and hippocampus [ 24 ]. Both genes increased significantly in the anhedonic animals, but their expression did not fall to control levels in the resilient animals, suggesting that Creb and Npy expression could be involved in stress protection.…”

Baicalin Rescues Cognitive Dysfunction, Mitigates Neurodegeneration, and Exerts Anti-Epileptic Effects Through Activating TLR4/MYD88/Caspase-3 Pathway in Rats

“…The model for the kindling procedure followed a previous method with minor modifications. 21 Briefly, the model group was intraperitoneally injected (i.p.) with a dose of the subcontinent (40 mg/kg) of PTZ, and the control group was administered an equal volume of saline for 28 days.…”

“…22 If there were a stage 5 seizure without remission that could intervene in death caused by convulsive symptoms during epileptic seizures in epileptic rats, an immediate injection of 10% chloral hydrate (5 mL/kg) should be used for sedation and anticonvulsion. 21,23 Animals were excluded from the study if they did not kindle (animals score less than stage 4 according to the Racine) after 28 days. 24,25…”