Sevim Şahin1, Seren Gülşen Gürgen2, Uğur Yazar3, İmran İnce4, Tülay Kamaşak5, Elif Acar Arslan5, Betül Diler Durgut6, Beril Dilber5, Ali Cansu5. 1. Department of Pediatric Neurology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. Electronic address: sevimsahin1@yahoo.com. 2. Department of Histology and Embriyology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. 3. Department of Neurosurgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. 4. Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. 5. Department of Pediatric Neurology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey. 6. Department of Pediatric Neurology, Maternity and Children Diseases Education and Research Hospital, Giresun University, Giresun, Turkey.
Abstract
OBJECTIVES: The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epileptic patients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats. METHODS: Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method. RESULTS: BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001). CONCLUSION: This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.
OBJECTIVES: The hippocampus is susceptible to damage in patients with epilepsy and in animals with seizures caused by excitotoxic agents. The effect of vitamin D on hippocampal apoptosis related with seizures has not been reported. However, epilepticpatients have an increased risk of hypovitaminosis D which is most likely due to the effects of antiepileptic drugs. Therefore, in this study, it was aimed to evaluate the effects of vitamin D on hippocampal apoptosis related with seizures by using pentylenetetrazol (PTZ) and kainic acid (KA) in rats. METHODS: Male Sprague Dawley rats, aged 5.5 weeks, were randomly divided into six groups: control, vitamin D, PTZ, KA, PTZ + vitamin D and KA + vitamin D groups. The groups that received vitamin D were given 500 IU/kg of vitamin D daily for two weeks in addition to a standard diet. At the end of this period, PTZ and KA were applied to trigger seizures in the rats in the seizure groups. 24 h after the administration of PTZ and KA, the rats were decapitated. In the hippocampal region, apoptosis was assessed by TUNEL and brain-derived neurotrophic factor (BDNF), Bax, caspase-3 and c-fos activation were evaluated by immunohistochemical method. RESULTS:BDNF level increased while c-fos, Bax and caspase-3 levels decreased (p < 0.0001, in all) in the hippocampal neurons of the groups that were pre-treated with vitamin D before the administration of PTZ and KA, in comparison with the PTZ and KA groups. Vitamin D significantly decreased the number of apoptotic cells in these rats in comparison with the PTZ and KA groups (p < 0.0001). CONCLUSION: This study indicates that vitamin D has neuroprotective effects on hippocampal apoptosis induced by PTZ and KA in rats. With this study it is suggested that keeping vitamin D levels within normal limits may be beneficial for patients with epilepsy, especially children.
Authors: Mark Obrenovich; Hayden Jaworski; Tara Tadimalla; Adil Mistry; Lorraine Sykes; George Perry; Robert A Bonomo Journal: Microorganisms Date: 2020-05-23