The Expression of ZnT3 and GFAP Is Potentiated in the Hippocampus of Drug-Resistant Epileptic Rats Induced by Amygdala Kindling

2020 ◽  
pp. 1-9
Author(s):  
Yuanxin Huang ◽  
Lin Wang ◽  
Siying Ren ◽  
Guofeng Wu ◽  
Jing Wu
Keyword(s):  
Healthy Adult ◽  
Mossy Fiber ◽  
Neuronal Degeneration ◽  
Anticonvulsant Drug ◽  
Drug Resistant ◽  
First Line ◽  
Sd Rats ◽  
Spontaneous Seizures ◽  
Healthy Adult Male ◽  
Amygdala Kindling

<b><i>Objective:</i></b> The first-line treatment for epilepsy, a chronic neurological disorder characterized by spontaneous seizures, includes the application of anticonvulsant drug therapy. Only one-third of patients are incapable of complete controlling of their seizures after the administration of ≥2 pharmaceuticals. Here, we aimed to observe the ultrastructure changes and the expression of ZnT3 and GFAP in the hippocampus of drug-resistant epileptic rats. <b><i>Methods:</i></b> A total of 50 healthy adult male SD rats were used to generate the model of<i></i>epilepsy by amygdala kindling. After the rats were successfully kindled, pharmacoresistant epileptic (PRE) rats were selected according to their response to phenobarbital and phenytoin. The ultrastructure as well as the expression of zinc transporter 3 (ZnT3, a member of a growing family of mammalian zinc transporters) and glial fibrillary acidic protein (GFAP) were compared among PRE, pharmacosensitive epileptic (PRE), and normal (NRC) rats. <b><i>Results:</i></b> The PRE rats displayed severe synapses, neuronal degeneration, and necrosis. Moreover, the expression of ZnT3 and GFAP was significantly increased in both PRE and PSE rats; compared with NRC rats, the promotion of this expression was more pronounced in the PRE rats. <b><i>Conclusions:</i></b> Taken together, obvious synapses, neuronal degeneration, necrosis, mossy fiber sprouting, and astrogliosis were found in the drug-resistant epileptic rat model induced by amygdala kindling.

scholarly journals The Heat Sensing Trpv1 Receptor Is Not a Viable Anticonvulsant Drug Target in the Scn1a+/− Mouse Model of Dravet Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Vaishali Satpute Janve ◽  
Lyndsey L. Anderson ◽  
Dilara Bahceci ◽  
Nicole A. Hawkins ◽  
Jennifer A. Kearney ◽  
...  
Keyword(s):  
Mouse Model ◽  
Drug Target ◽  
Genetic Modifier ◽  
Anticonvulsant Drug ◽  
Dravet Syndrome ◽  
Seizure Threshold ◽  
Drug Resistant ◽  
Spontaneous Seizures ◽  
Temperature Thresholds ◽  
Seizure Models

Cannabidiol has been approved for the treatment of drug-resistant childhood epilepsies including Dravet syndrome (DS). Although the mechanism of anticonvulsant action of cannabidiol is unknown, emerging data suggests involvement of the transient receptor potential cation channel subfamily V member 1 (Trpv1). Pharmacological and genetic studies in conventional seizure models suggest Trpv1 is a novel anticonvulsant target. However, whether targeting Trpv1 is anticonvulsant in animal models of drug-resistant epilepsies is not known. Thus, we examined whether Trpv1 affects the epilepsy phenotype of the F1.Scn1a+/− mouse model of DS. We found that cortical Trpv1 mRNA expression was increased in seizure susceptible F1.Scn1a+/− mice with a hybrid genetic background compared to seizure resistant 129.Scn1a+/− mice isogenic on 129S6/SvEvTac background, suggesting Trpv1 could be a genetic modifier. Previous studies show functional loss of Trpv1 is anticonvulsant. However, Trpv1 selective antagonist SB-705498 did not affect hyperthermia-induced seizure threshold, frequency of spontaneous seizures or survival of F1.Scn1a+/− mice. Surprisingly, Trpv1 deletion had both pro- and anti-seizure effects. Trpv1 deletion did not affect hyperthermia-induced seizure temperature thresholds of F1.Scn1a+/−; Trpv1+/− at P14-16 but was proconvulsant at P18 as it reduced seizure temperature thresholds. Conversely, Trpv1 deletion did not alter the frequency of spontaneous seizures but reduced their severity. These results suggest that Trpv1 is a modest genetic modifier of spontaneous seizure severity in the F1.Scn1a+/− model of DS. However, the opposing pro- and anti-seizure effects of Trpv1 deletion and the lack of effects of Trpv1 inhibition suggest that Trpv1 is unlikely a viable anticonvulsant drug target in DS.

Cognitive Impairment and Mossy Fiber Sprouting in a Rat Model of Drug-Resistant Epilepsy Induced by Lithium–Pilocarpine

2021 ◽  
Vol 18 ◽  
Author(s):  
Jing Wu ◽  
Likun Wang ◽  
Yuanxin Huang ◽  
Qian Wu ◽  
Xingmei Luo ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cognitive Impairment ◽  
Spatial Memory ◽  
Seizure Frequency ◽  
Rat Model ◽  
Memory Impairment ◽  
Mossy Fiber ◽  
Drug Resistant ◽  
Spontaneous Seizures ◽  
Drug Resistant Epilepsy

Background: The mossy fiber sprouting (MFS) in the dentate gyrus is a common pathological change of epilepsy. Previous studies suggested that it is associated with drug-resistant epilepsy, and mossy cells control spontaneous seizures and spatial memory. Methods: We investigated the correlations among cognitive impairment, MFS, seizure frequency and drug resistance in a rat model of epilepsy induced by lithium–pilocarpine. Phenytoin and phenobarbital were used to screen drug resistance. Cognitive function and MFS were detected through the novel object recognition (NOR) test, Morris water maze (MWM) test and Timm staining. Results: The results showed that object memory and spatial memory functions were both significantly impaired in rats with epilepsy, and only spatial memory impairment was more severe in rats with drug-resistant epilepsy. More frequent spontaneous seizures and more obvious MFS were observed in the drug-resistant rats. The seizure frequency was significantly associated with the MWM performance but not with the NOR performance in rats with epilepsy. The degree of MFS was significantly associated with seizure frequency and spatial memory function. Conclusion: Taken together, these correlations among drug resistance, seizure frequency, spatial memory impairment and MFS suggested the possibility of a common pathological mechanism. More studies are needed to clarify the underlying mechanism behind these correlations and the detailed role of MFS in epilepsy. The mechanism of mossy cell change may be an important target for the treatment of seizures, drug resistance and cognitive dysfunction in patients with epilepsy.

Safety and Tolerance ofLactobacillus reuteriin Healthy Adult Male Subjects

1994 ◽  
Vol 8 (2) ◽  
Author(s):  
B. W. Wolf ◽  
K. A. Garleb ◽  
D. G. Ataya ◽  
I. A. Casas
Keyword(s):  
Adult Male ◽  
Healthy Adult ◽  
Healthy Adult Male ◽  
Male Subjects

scholarly journals Dobutamine stress echocardiography in healthy adult male rats

2005 ◽  
Vol 3 (1) ◽  
Author(s):  
Eric Plante ◽  
Dominic Lachance ◽  
Marie-Claude Drolet ◽  
Élise Roussel ◽  
Jacques Couet ◽  
...  
Keyword(s):  
Adult Male ◽  
Stress Echocardiography ◽  
Healthy Adult ◽  
Dobutamine Stress Echocardiography ◽  
Dobutamine Stress ◽  
Male Rats ◽  
Healthy Adult Male
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