Antiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy

Tchekalarova, Jana; Ivanova, Natasha; Pechlivanova, Daniela; Atanasova, Dimitrinka; Lazarov, Nikolai; Kortenska, Lidia; Mitreva, Rumyana; Lozanov, Valentin; Stoynev, Alexander

doi:10.1016/j.pbb.2014.10.005

Cited by 50 publications

(49 citation statements)

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“…Kainic acid was diluted in sterile saline (0.9% NaCl) at 2.5 mg/ml. The protocol of KA-induced SE was executed according to [15]. In brief, SE was induced by repetitive injections of KA (Abcam, UK) starting with a dose of 5 mg/kg, i.p.…”

Section: Induction Of Status Epilepticus With Kainic Acidmentioning

confidence: 99%

“…The sections were investigated on a Nikon Eclipse 80i light microscope (Japan) and photographed with a digital camera (Nikon DMX 1200). Sections were analyzed for major cell loss with special attention to the dorsal and ventral hippocampi as previously described [22]. The staining intensity and density of nerve cell bodies were estimated using Nikon's NIS Elements Digital Imaging software.…”

Section: Histologymentioning

confidence: 99%

“…Repetitive seizures induced in an experimental model of TLE caused an upregulation of the components of RAS, ACE (angiotensin-converting enzyme), and the AT 1 receptor expression in the hippocampus of Wistar audiogenic rats [13] and the pilocarpine model of TLE [14]. The longterm treatment with losartan after kainate (KA)-induced status epilepticus (SE) has been found to increase the latency for onset of the first spontaneous seizure and to prevent some of the deleterious consequences accompanying the chronic epileptic state in rats [15].…”

Section: Introductionmentioning

confidence: 99%

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Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes

Ivanova

Atanasova

Pechlivanova

et al. 2015

Epilepsy & Behavior

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Section: Induction Of Status Epilepticus With Kainic Acidmentioning

confidence: 99%

Section: Histologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes

Ivanova

Atanasova

Pechlivanova

et al. 2015

Epilepsy & Behavior

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“…The protocol of KA-induced SE was executed according to Hellier et al 13 with a minor modifcation 14 . Status epilepticus was induced in Sed-KA and Ex-KA groups by repetitive injections of KA (Abcam, UK) starting at a dose of 5 mg.kg -1 , i.p.…”

Section: Induction Of Status Epilepticus With Kainic Acidmentioning

confidence: 99%

“…Seizure intensity was evaluated by a modifi ed Racine's scale as described previously. 14 The kainate treatment continued until sustained seizures of class III, IV or V (i.e. >9 motor seizures.h -1 ) were observed.…”

Section: Induction Of Status Epilepticus With Kainic Acidmentioning

confidence: 99%

Effect of Training at Lactate Threshold Intensity on Maximal Time to Exhaustion, Depression and Anxiety Behaviour of Spontaneously Hypertensive Rats after Kainate-Induced Status Epilepticus

Georgieva¹,

Hadjieva²,

Shishmanova-Doseva³

et al. 2017

Folia Medica

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Citation: Georgieva KN, Hadjieva MS, Doseva MS, Terzieva DD, Georgiev NG, Andreev GG, Tchekalarova JD. Eff ect of training at lactate threshold intensity on maximal time to exhaustion, depression and anxiety behaviour of spontaneously hypertensive rats after kainate-induced status epilepticus.Folia Medica 2017;59(1): 91-97. doi: 10.1515/folmed-2017-0004 Aim: The objective of the present study was to investigate the eff ect of treadmill training at lactate threshold intensity on maximum time to exhaustion (MTE) and heart rate (HR) as well as behavioral changes after kainate (KA)-induced status epilepticus (SE) of spontaneously hypertensive rats (SHRs). Materials and methods: Male SHRs were divided in four groups: two sedentary (vehicle-and KA-treated) and two exercised (vehicle-and KA-treated), respectively. The exercised rats were trained on a treadmill at a speed of 20 m.min -1 and 0º elevation for 40 min.d -1 , for 4 wk. Maximal time to exhaustion and HR was measured at the beginning and at the end of the training period. Status epilepticus was evoked in half of the sedentary and trained rats by a repetitive intraperitoneal injection of KA in low subconvulsive doses. The other half of the groups received saline. Sucrose preference test (SPT) for depression-like behavior and hole board test (HBT) for impulsivity were performed a month after KA/veh injection. Results:The maximum time of exhaustion was elongated in the SHRs at the end of the training period in comparison with the beginning. However, no eff ect on HR was detected in trained rats. Kainate treatment after one month of training alleviated the SE-induced anhedonia in SPT and stereotyped behavior in HBT, respectively. Conclusions: Taken together, these results demonstrate that exercise exerts a benefi cial infl uence on physical working capacity, depression and impulsive behavior in a co-morbid model of essential hypertension and SE.

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Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension

Doege¹,

Luedde

Kostev³

2022

JAMA Neurol

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ImportanceArterial hypertension is associated with an increased incidence of epilepsy. Results from animal studies suggest that angiotensin receptor blocker (ARB) therapy could inhibit epileptic seizures. However, there is a lack of clinical data to support the use of ARB therapy in humans.ObjectiveTo assess whether ARB therapy is associated with a decreased incidence of epilepsy in patients with hypertension.Design, Setting, and ParticipantsThis cohort study obtained data from the Disease Analyzer database (IQVIA) on patients aged 18 years or older who had hypertension and at least 1 antihypertensive drug prescription. Patients were treated at 1274 general practices between January 2010 and December 2020 in Germany. Data were available for 1 553 875 patients who had been prescribed at least 1 antihypertensive drug. Patients diagnosed with epilepsy before or up to 3 months after the index date were excluded. A total of 168 612 patients were included in propensity score matching. Patients treated with 1 of 4 antihypertensive drug classes (β-blockers, ARBs, angiotensin-converting enzyme inhibitors, and calcium channel blockers [CCBs]) were matched to each other using propensity scores.Main Outcomes and MeasuresThe main outcome of the study was the incidence of epilepsy associated with ARB therapy compared with other antihypertensive drug classes. Cox regression models were used to study the association between the incidence of epilepsy and ARBs compared with all other antihypertensive drug classes as a group.ResultsThe study included a total of 168 612 patients, with 42 153 in each antihypertensive drug class. The mean [SD] age of patients was 62.3 [13.5] years, and 21 667 (51.4%) were women. The incidence of epilepsy within 5 years was lowest among patients treated with ARBs (0.27% at 1 year, 0.63% at 3 years, 0.99% at 5 years) and highest among patients receiving β-blockers and CCBs (0.38% for both β-blockers and CCBs at 1 year; 0.91% for β-blockers and 0.93% for CCBs at 3 years; β-blockers, 1.47%; and CCBs, 1.48% at 5 years). Angiotensin receptor blocker therapy was associated with a significantly decreased incidence of epilepsy (hazard ratio, 0.77; 95% CI, 0.65-0.90) compared with the other drug classes as a group.Conclusions and RelevanceIn this cohort study of patients with hypertension, ARB therapy was associated with a significantly decreased incidence of epilepsy. The findings suggest antihypertensive drugs could be used as a novel approach for preventing epilepsy in patients with arterial hypertension.

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Antiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy

Cited by 50 publications

References 57 publications

Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes

Long-term intracerebroventricular infusion of angiotensin II after kainate-induced status epilepticus: Effects on epileptogenesis, brain damage, and diurnal behavioral changes

Effect of Training at Lactate Threshold Intensity on Maximal Time to Exhaustion, Depression and Anxiety Behaviour of Spontaneously Hypertensive Rats after Kainate-Induced Status Epilepticus

Association Between Angiotensin Receptor Blocker Therapy and Incidence of Epilepsy in Patients With Hypertension

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