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Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy

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Abstract

Over the last 10 years, accumulated experimental and clinical evidence has supported the idea that AT1 receptor subtype is involved in epilepsy. Recently, we have shown that the selective AT1 receptor antagonist losartan attenuates epileptogenesis and exerts neuroprotection in the CA1 area of the hippocampus in epileptic Wistar rats. This study aimed to verify the efficacy of long-term treatment with losartan (10 mg/kg) after kainate-induced status epilepticus (SE) on seizure activity, behavioral and biochemical changes, and neuronal damage in a model of co-morbid hypertension and epilepsy. Spontaneous seizures were video- and EEG-monitored in spontaneously hypertensive rats (SHRs) for a 16-week period after SE. The behavior was analyzed by open field, elevated plus maze, sugar preference test, and forced swim test. The levels of serotonin in the hippocampus and neuronal loss were estimated by HPLC and hematoxylin and eosin staining, respectively. The AT1 receptor antagonism delayed the onset of seizures and alleviated their frequency and duration during and after discontinuation of treatment. Losartan showed neuroprotection mostly in the CA3 area of the hippocampus and the septo-temporal hilus of the dentate gyrus in SHRs. However, the AT1 receptor antagonist did not exert a substantial influence on concomitant with epilepsy behavioral changes and decreased 5-HT levels in the hippocampus. Our results suggest that the antihypertensive therapy with an AT1 receptor blocker might be effective against seizure activity and neuronal damage in a co-morbid hypertension and epilepsy.

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Acknowledgments

This work was supported by contract No. 30/2011 and National Science Fund (Research Grant # DTK 02/56 2009-2012). The authors thank Sabina Mitova, Medical Department, Medical University, Sofia for her expert technical assistance with the study.

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Authors and Affiliations

  1. Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 23, 1113, Sofia, Bulgaria

    Jana D. Tchekalarova, Natasha Ivanova, Dimitrina Atanasova, Daniela M. Pechlivanova, Lidia Kortenska & Rumiana Mitreva

  2. Department of Anatomy, Medical Faculty, MU-Sofia, Sofia, Bulgaria

    Nikolai Lazarov

  3. Department of Medical Chemistry and Biochemistry, Sofia, Bulgaria

    Valentin Lozanov

  4. Department of Pathophysiology, Medical Faculty, MU-Sofia, Sofia, Bulgaria

    Alexander Stoynev

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  1. Jana D. Tchekalarova
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  2. Natasha Ivanova
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  3. Dimitrina Atanasova
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Correspondence to Jana D. Tchekalarova.

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Tchekalarova, J.D., Ivanova, N., Atanasova, D. et al. Long-Term Treatment with Losartan Attenuates Seizure Activity and Neuronal Damage Without Affecting Behavioral Changes in a Model of Co-morbid Hypertension and Epilepsy. Cell Mol Neurobiol 36, 927–941 (2016). https://doi.org/10.1007/s10571-015-0278-3

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