Effects of in utero exposure to valproate or levetiracetam on the seizures and newborn histopathology of genetic absence epilepsy rats

Kantarcı, Berk Can; Şanlı, Ahmet Necati; Gavaş, Şeyhmus; Toplu, Aylin; Çilingir‐Kaya, Özlem Tuğçe; İdrizoğlu, Medine Gülçebi; Ercan, Feriha; Onat, Filiz

doi:10.1016/j.neulet.2022.136574

Cited by 4 publications

(1 citation statement)

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“…We should also be cautious about this conclusion, because the evaluations provided by caregivers were subjective and might lack standards to measure behaviour and cognition for DEE ( Strzelczyk and Schubert-Bast, 2022 ). Berk et al found that in the offspring of LEV group, the alveolar epithelium thickened, the Bowman’s space in renal corpuscles dilated, and the brain cortex irregularly thickened, all indicating that LEV has deleterious effects on the lungs, kidneys and brains of newborns, when 100 mg/kg LEV were intraperitoneally injected before pregnancy of Genetic Absence Epilepsy Rats from Strasbourg rats ( Can et al, 2022 ). These results were not similar to that of our study, which might be due to the prenatal susceptibility of rats and different models.…”

Section: Discussionmentioning

confidence: 99%

Levetiracetam attenuates diabetes-associated cognitive impairment and microglia polarization by suppressing neuroinflammation

et al. 2023

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Introduction: Cognitive impairment is a common complication and comorbidity of diabetes. However, the underlying mechanisms of diabetes-associated cognitive dysfunction are currently unclear. M1 microglia secretes pro-inflammatory factors and can be marked by CD16, iNOS, Iba1 and TNF-ɑ. The decline of M2 microglia in the diabetic rats indicates that high glucose promotes the differentiation of microglia into the M1 type to trigger neuroinflammatory responses. Moreover, there is a lack of strong evidence for treatments of diabetes-associated cognitive impairment in addition to controlling blood glucose.Methods: Diabetic rats were established by intraperitoneal injection of one dose of streptozotocin (60 mg/kg). Polarization transitions of microglia were induced by high glucose treatment in BV2 cells. Levetiracetam was orally administered to rats 72 h after streptozotocin injection for 12 weeks.Results: In STZ-induced diabetic rats, the results demonstrated that levetiracetam improved rat cognitive function (Morris water maze test) and hippocampus morphology (Hematoxylin-eosin staining), and the effect was more evident in the high-dose levetiracetam group. Microglia activation in the hippocampus was inhibited by levetiracetam treatment for 12 weeks. Serum levels of TNF-α, IL-1β, and IL-6 were reduced in the LEV-L and LEV-H groups, and IL-1β level was obviously reduced in the LEV-H group. In vitro, we found that levetiracetam 50 µM attenuated high-glucose induced microglial polarization by increasing IL-10 level and decreasing IL-1β and TNF-α levels. Moreover, levetiracetam 50 µM increased and decreased the proportion of CD206+/Iba1+ and iNOS+/Iba1+cells, respectively. Western blot analysis illustrated that LEV 50 µM downregulated the expression of MyD88 and TRAF6, and phosphorylation of TAK1, JNK, p38, and NF-κB p65. The effect of levetiracetam on the anti-polarization and expression of p-JNK and p-NF-κB p65 were partly reversed by anisomycin (p38 and JNK activators).Discussion: Together, our data suggest that levetiracetam attenuates streptozotocin-induced cognitive impairment by suppressing microglia activation. The in vitro findings also indicate that the levetiracetam inhibited the polarization of microglia via the JNK/MAPK/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%