Metehan Akça

The Effects of Prenatal Exposure to a 900 Megahertz Electromagnetic Field on Hippocampus Morphology and Learning Behavior in Rat Pups

This study was planned to examine the effect on hippocampus morphology and learning behavior in rat pups exposed to a 900 megahertz (MHz) electromagnetic field (EMF) in the prenatal period. Sprague Dawley rats weighing 180-250 g at the beginning of the study and with a regular cycle were left to mate with male rats. The following day, rats identified as pregnant using the vaginal smear test were divided into two groups; control (n=3) and EMF (n=3). No procedure was performed in the control group. The EMF group was exposed to 900 MHz EMF for 1h per day on days 13 to 21 of pregnancy. Female rat pups were removed from their mothers at 21 days old. Two newborn rat groups were then established, a 13 member control group and a 10 member EMF group. We foresaw that maternal separation anxiety might develop in the rat pups, and behavioral tests commenced 4 days later. Radial arm maze and passive avoidance tests measuring learning and memory performance and the open field test to evaluate locomotor activities were applied. All rats were decapitated on the 32nd day of the study and brain tissues removed. These were fixed in paraffin and underwent routine histological tissue analyses. Sections were taken, stained with Cresyl fast violet and subjected to histopathological examination. Positive effects on learning behavior were determined in the EMF group rats in the radial arm maze (p=0.007) and passive avoidance (p=0.037) tests, administered to both groups under identical conditions, while no statistically significant difference was determined in the open field test (p=0.05) results. The absence of any statistical difference in the open field test shows that the animals were not exposed to any stress during application of the test. No pathology was determined in the control group at histopathological examination of the sections. In contrast, neuronal and morphological compromise was observed in the EMF group. Our results show that exposure to a 900 MHz EMF in the prenatal period had an adverse effect on female pups learning behavior and also caused histopathological changes in the hippocampus.

Penicillin induced epileptiform activity and EEG spectrum analysis of BDNF heterozygous mice: an in vivo electrophysiological study.

Brain-derived neurotrophic factor (BDNF) heterozygous mice (BDNF (+/-)) kindle slowly and have a higher seizure threshold. However, BDNF (+/-) mice exhibit reduced cortical inhibition and disrupted balance of excitation/inhibition synaptic transmission. We investigated penicillin-induced focal cortical epileptiform activity and electroencephalogram (EEG) spectral power of BDNF (+/-) mice, by using electrocorticogram (ECoG) recordings. BDNF (+/-) mice (n=10) and wild type littermates (n=9) were anesthetized with i.p. urethane (1.750g/kg). The recordings of ECoG were carried out by using a data acquisition system and 100IU penicillin was administered intracortically to induce epileptiform activity. The latencies for the onset of spikes and the amplitude of the spikes showed no differences. However the frequency of the spikes was significantly lower in BDNF (+/-) mice at 40th and 45th min following penicillin injection. Additionally, the EEG power for both BDNF (+/-) and wild type mice reduced after penicillin injection and enhanced during epileptiform activity. The spectral power analysis also revealed that the absolute Gamma power of BDNF (+/-) was significantly smaller than wild types. The results of the present study provide the first in vivo electrophysiological evidence that BDNF heterozygous mice exhibited suppressed epileptiform activity. Moreover, reduced levels of BDNF led to a reduction of absolute Gamma band power.

Comparison of focally induced epileptiform activities in C57BL/6 and BALB/c mice by using in vivo EEG recording

Epilepsy characterized by repeated seizures is influenced by genetic factors. Seizure response of inbred mouse strains changes depending on the variety of stimuli including chemical (e.g., pentylenetetrazole, nicotine, cocaine, NMDA, kainate), physical (e.g., auditory) or electrical. In this study, we compared the susceptibilities of C57BL/6 and BALB/c mice strains to penicillin induced epileptiform activity (a focally induced, experimental epilepsy model), by analyzing the spike onset latency, spike amplitude and spike frequency. The power spectrums of baseline EEGs were also investigated. We found no alterations of spike onset latencies between the C57 and BALB mice. However, spike amplitudes and spike frequencies were found to be higher in BALB mice than C57 mice. With regard to EEG power spectrum, absolute power of investigated bands was not different between the two strains. Interestingly, the relative power of all investigated bands differed significantly between two strains. The relative power of delta and theta was lower whereas relative power of alpha, beta and gamma was higher in C57 mice compared to BALB mice. In conclusion, our findings showed that BALB mice are more sensitive to penicillin induced epileptiform activity when compared to C57 strain.

Efficacy of dexamethasone on penicillin-induced epileptiform activity in rats: An electrophysiological study

Corticosteroids are extensively used in treatment of many diseases. In neurosurgery practice, dexamethasone (DEX) is commonly used particularly in cerebral edema secondary to brain tumors, head trauma, and central nervous system infections. There are some uncertainties surrounding the secure use of DEX in patients with epilepsy or seizures induced by diseases of the central nervous system such as head trauma and brain tumors. Despite its extensive use, the effect of DEX on epileptiform activity is unclear. In this study the effect of DEX on epileptiform activity was investigated in rats. The effects of 1, 3, and 10mg/kg DEX on epileptiform activity was compared with effects of antiepileptic drugs commonly employed in treatment of epilepsy, namely phenytoin (PHT) 50mg/kg and levetiracetam (LEV) 50mg/kg that were administered intraperitoneally for 1 week. All groups were administered intracortical penicillin (500IU) to induce epileptiform activity. DEX at the doses of 3mg/kg and 10mg/kg significantly reduced spike frequencies compared to the initial values. In conclusion, we think that DEX can effectively decrease the epileptiform activity.

Electrophysiological evidence for the anticonvulsant effect of alpha-lipoic acid via indirect antioxidant properties in BALB/c mice

Abstract Alpha-lipoic acid (alpha-LA) is a strong antioxidant whose effect on epilepsy has not been completely clarified yet. The present study was designed to investigate the effects of alpha-LA on epileptiform activity induced by penicillin in BALB/c mice. In the present study, 56 adult male BALB/c mice were divided into seven groups. Under urethane anesthesia, the mice were injected with intracortical (i.c.) 200 IU penicillin following craniotomy to start epileptiform activity. The effects of alpha-LA on epileptiform activity were examined through the intraperitoneal (i.p.) application of 25, 50, 100, 200, and 400 mg/kg doses. The electrophysiological data have demonstrated that alpha-LA at the 200 mg/kg dose showed an anticonvulsant effect by reducing penicillin-induced epileptiform activity. This effect obtained at the 200 mg/kg dose was determined to emerge 80 minutes after injection (i.p.) and last throughout the experiment. Alpha-LA (400 mg/kg) was appointed as the toxic dose for the BALB/c mice used in this study. The findings of the study indicate that alpha-LA at the 200 mg/kg dose show an anticonvulsant effect by reducing penicillin-induced epileptiform activity. Besides this, the delayed anticonvulsant effect of alpha-LA observed in this study gives the impression that it could result from its indirect antioxidant activity.

Electrophysiological evidence on epileptiform activity enhanced by electrical stimulation of teeth in rats

Abstract The aim of this study was to evaluate the possible effects of electrical stimulation (ES) of tooth on penicillin-induced epileptiform activity in rats. Experiment was realized on 24 adult male Sprague Dawley rats. Rats were assigned three groups [stimulation group (SG), penicillin group (PG), and penicillin+stimulation group (PSG)]. In SG, ES was only applied. Ten pulses of electrical current were delivered to the teeth for a duration of 2 milliseconds at 1-second intervals from a stimulator. Currents were applied in the range of 40–240 μA with 40 μA steps. Electrocorticography (ECoG) recordings were taken before and after ES. In PG, ECoG recordings were taken before and during the injection of penicillin. In PSG, after epileptiform activity was induced, ES was applied and ECoG recordings were taken as in SG. All the data were analyzed with Student’s t test. Applied currents did not cause any epileptiform activity in SG. When the PSG was compared with the PG it was seen that the spike frequency of epileptiform activity increased in a statistically significant way after application of 240 μA (P < 0·05). On the other hand current application caused an increase in the spike amplitude of the PSG compared with the amplitude of the PG, but it was not statistically significant. We concluded that ES of tooth with high current can trigger epileptiform activity in rats. For this reason, further research is required to evaluate the effects of ES of tooth for pulp testing on epileptic human subjects and antiepileptic drug users.