Differential effects of levetiracetam on hippocampal CA1 synaptic plasticity and molecular changes in the dentate gyrus in epileptic rats

Salaka, Raghava Jagadeesh; Nair, Kala P.; Sasibhushana, R B; Udayakumar, Deepashree; Kutty, Bindu M.; Srikumar, B.N.; Rao, B S Shankaranarayana

doi:10.1016/j.neuint.2022.105378

Cited by 6 publications

(10 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Isolated modulation of seizure thresholds without affecting underlying cortical excitability has been observed in animal research, possibly through the modulation of specific neuronal firing patterns. [48][49][50] For example, lacosamide (the most common adjunctive ASM in this study) has been hypothesized to terminate sustained repetitive firing over seconds through a slow inactivation of sodium channels without impacting excitability at shorter time scales. 50 Our study emphasizes the need to investigate these possible mechanisms, as well as their comparative advantages and disadvantages.…”

Section: Discussionmentioning

confidence: 99%

Seizure Cycles under Pharmacotherapy

Friedrichs‐Maeder,

Proix,

Tcheng

et al. 2024

Annals of Neurology

View full text Add to dashboard Cite

ObjectiveThis study was undertaken to determine the effects of antiseizure medications (ASMs) on multidien (multiday) cycles of interictal epileptiform activity (IEA) and seizures and evaluate their potential clinical significance.MethodsWe retrospectively analyzed up to 10 years of data from 88 of the 256 total adults with pharmacoresistant focal epilepsy who participated in the clinical trials of the RNS System, an intracranial device that keeps records of IEA counts. Following adjunctive ASM trials, we evaluated changes over months in (1) rates of self‐reported disabling seizures and (2) multidien IEA cycle strength (spectral power for periodicity between 4 and 40 days). We used a survival analysis and the receiver operating characteristics to assess changes in IEA as a predictor of seizure control.ResultsAmong 56 (33.3%) of the 168 adjunctive ASM trials suitable for analysis, ASM introduction was followed by an average 50 to 70% decrease in multidien IEA cycle strength and a concomitant 50 to 70% decrease in relative seizure rate for up to 12 months. Individuals with a ≥50% decrease in IEA cycle strength in the first 3 months of an ASM trial had a higher probability of remaining seizure responders (≥50% seizure rate reduction, p < 10−7) or super‐responders (≥90%, p < 10−8) over the next 12 months.InterpretationIn this large cohort, a decrease in multidien IEA cycle strength following initiation of an adjunctive ASM correlated with seizure control for up to 12 months, suggesting that fluctuations in IEA mirror “disease activity” in pharmacoresistant focal epilepsy and may have clinical utility as a biomarker to predict treatment response. ANN NEUROL 2024

show abstract

Section: Discussionmentioning

confidence: 99%

Seizure Cycles under Pharmacotherapy

Friedrichs‐Maeder,

Proix,

Tcheng

et al. 2024

Annals of Neurology

View full text Add to dashboard Cite

show abstract

“…Finasteride 100 mg/Kg: rats administered with 100 mg/Kg finasteride (2 mL/Kg, s.c., Fin 100), n = 11–12 for all behavioral studies, n = 4–5 for ELISA, and n = 8–10 rats for electrophysiology. The sample size was calculated in accordance with the previous studies (Salaka et al., 2022; Sasibhushana et al., 2019; Subhadeep et al., 2017).…”

Section: Methodsmentioning

confidence: 99%

“…The hippocampal slices were then transferred to a slice incubating chamber (BSK4‐Quad; AutoMate Scientific Inc., CA, USA, ) filled with carbogenated aCSF. These slices were incubated in slice keeper for 2 h at room temperature (Salaka et al., 2021, 2022; Subhadeep et al., 2021).…”

Section: Methodsmentioning

confidence: 99%

“…The following groups were used for the study: Vehicle control: and n = 8-10 rats for electrophysiology. The sample size was calculated in accordance with the previous studies (Salaka et al, 2022;Sasibhushana et al, 2019;Subhadeep et al, 2017).…”

Section: Experimental Design and Groupsmentioning

confidence: 99%

“…Normalized slope of fEPSPs was averaged and considered for analysis. PTP, STP, and LTP were obtained by considering first min, 30-40 min, and last 20 min slope value of fEPSP, respectively, after TBS(Salaka et al, 2021(Salaka et al, , 2022Subhadeep et al, 2021).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Repeated finasteride administration promotes synaptic plasticity and produces antidepressant‐ and anxiolytic‐like effects in female rats

Nayana,

Shankaranarayana Rao,

Srikumar

2024

J of Neuroscience Research

Self Cite

View full text Add to dashboard Cite

Finasteride is used in female‐pattern hair loss, hirsutism, and polycystic ovarian syndrome. It inhibits 5α‐reductase, which is an important enzyme in the biosynthesis of neurosteroids. The effects of finasteride treatment on mental health in female patients as well as the effects of repeated/chronic finasteride administration in female rodents are still unknown. Accordingly, in our study, we administered finasteride (10, 30, or 100 mg/Kg, s.c.) for 6 days in female rats and evaluated behavior, plasma steroid levels, and synaptic plasticity. Depression‐like behavior was evaluated using forced swim test (FST) and splash test. Anxiety‐like behavior was evaluated using novelty‐suppressed feeding task (NSFT), elevated plus maze (EPM), open field test (OFT), and light–dark test (LDT). Plasma steroid levels were assessed using ELISA and synaptic plasticity by field potential recordings. We observed that finasteride decreased total immobility duration in FST, indicating antidepressant‐like effect and decreased the latency to first bite in NSFT, showing anxiolytic‐like effect. We also found a significant increase in plasma estradiol and a significant decrease in plasma corticosterone level. Furthermore, field potential recordings showed that finasteride increased hippocampal long‐term potentiation. These results indicate that repeated finasteride administration in female rats may have antidepressant‐ and anxiolytic‐like effect, which might be mediated by enhanced estradiol levels or decreased corticosterone levels. Further studies are required to validate the molecular mechanisms underlying the effects of finasteride in female rats. Understanding the mechanisms will help us in developing novel neurosteroid‐based therapeutics in the treatment of neuropsychiatric disorders in women.

show abstract

Impact of levetiracetam on cognitive impairment, neuroinflammation, oxidative stress, and neuronal apoptosis caused by lipopolysaccharides in rats

Mani

Almutairi

2023

Saudi Pharmaceutical Journal

View full text Add to dashboard Cite

Differential effects of levetiracetam on hippocampal CA1 synaptic plasticity and molecular changes in the dentate gyrus in epileptic rats

Cited by 6 publications

References 70 publications

Seizure Cycles under Pharmacotherapy

Seizure Cycles under Pharmacotherapy

Repeated finasteride administration promotes synaptic plasticity and produces antidepressant‐ and anxiolytic‐like effects in female rats

Impact of levetiracetam on cognitive impairment, neuroinflammation, oxidative stress, and neuronal apoptosis caused by lipopolysaccharides in rats

Contact Info

Product

Resources

About