Quantitative Analysis of the Antiepileptogenic Effects of Low Frequency Stimulation Applied Prior or After Kindling Stimulation in Rats

Background and Objective: Developing quantitative measures based on spectral analysis of electroencephalograph (EEG) recordings of neural activities plays an important role in developing efficient treatments for epilepsy. Such biomarkers can be used for developing open or closed loop approaches for seizure prediction or prevention. This study aims to quantitatively evaluate antiepileptogenic effects of low frequency stimulation (LFS) applied immediately before or after kindling stimulations using spectral power analysis of extracellular EEG in rat.Methods: Nineteen adult rats were used: seven for kindle, six for LFS+Kindle (LFSK) and six for Kindle+LFS (KLFS). Four packages of LFS (1Hz) were applied immediately before or after rapid kindling stimulations. The power spectral densities of afterdischarge (AD) sections of EEG corresponding to different stages of kindling for delta (0–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), beta (12–28 Hz), gamma (28–40 Hz) sub-bands, and theta/alpha ratio were comparatively investigated. Moreover, correlation between AD duration (ADD) and its different frequency components was calculated.Results: Both LFSK and KLFS significantly increased delta and reduced beta and gamma oscillations, compared with kindle group. However, just the reduction in LFSK group was significant. Both protocols increased theta/alpha ratio, but just LFSK showed significant increase (p < 0.05). Although LFSK enhanced theta/alpha ratio more than KLFS, the difference was not statistically significant. Furthermore, strong correlation between each frequency sub band and ADD was not observed in kindle and LFS treated groups (both LFSK and KLFS).Conclusion: Although behavioral assessments showed relatively the same level of antiepileptogenic effects for KLFS and LFSK, quantitative assessments showed more significant differences in the quantitative measures between the two protocols. Developing more quantitative EEG based measures correlated with LFS-induced effects can facilitate developing open or closed loop seizure prevention modalities

The effect of electrical low-frequency stimulation on balance and locomotor activity in adult male rats during epileptogenesis of dorsal hippocampal

Background: Epilepsy is the third world neurological disorder. Epileptic focus causes motor impairment by sending projections to different areas of the brain such as areas which are related to movement control. Regarding the inhibitory effect of low-frequency electrical stimulation (LFS) on seizure wave's transmission, this study aimed at examining the effect of LFS during the epileptogenesis of dorsal hippocampal on balance and locomotor activity in adult male rats using the kindling method. Materials and Methods: Fifty rats were randomly divided into 5 groups: Control, Sham, Kindled, LFS and KLFS. Animals in the kindled group were stimulated rapidly by daily stimulation of dorsal hippocampus (1 ms pulse duration at 50Hz for 3 seconds). Animals in the sham and control groups did not receive any stimulation. In the LFS groups, four LFS packages at a frequency of 1 Hz were applied daily. At the end of stimulation, motor activity and balance were assessed by open-field and rotarod tests. Results: Frequency of rearing and grooming in the Kindled group significantly increased compared to the control group (P<0.05). Balance in the Kindled group was significantly decreased (P<0.05). LFS induction during hippocampal kindling did not show any significant difference in any of the mentioned parameters with the control group. Conclusion: In summary, applying low-frequency electrical stimulation during hippocampal kindling can reduce the motor activity and improve balance

Low Frequency Electrical Stimulation Either Prior to Or after Rapid Kindling Stimulation Inhibits the Kindling-Induced Epileptogenesis

Objective. Studies are ongoing to find appropriate low frequency stimulation (LFS) protocol for treatment of epilepsy. The present study aimed at assessing the antiepileptogenesis effects of LFS with the same protocol applied either just before or immediately after kindling stimulations. Method. This experimental animal study was conducted on adult Wistar rats (200 ± 20 g) randomly divided into kindle (n=7), LFS + Kindle (n=6), and Kindle + LFS groups (n=6). All animals underwent rapid kindling procedure and four packages of LFS (1 Hz) with 5 min interval were applied either immediately before (LFS-K) or after kindling stimulation (K-LFS). The after discharge duration (ADD), daily stages of kindling, and kindling seizure stage and number of stimulations required to reach each stage were compared between the three groups using two-way analysis of variance (ANOVA) followed by Tukey post hoc and one-way ANOVA, and Kruskal-Wallis test, respectively. Results. LFS in both protocols significantly decreased the ADD (p0.05, stages 3 to 5: p<0.05). Conclusion. Although LFS-K showed more inhibiting effect than K-LFS, the difference was not statistically significant

Study the Effect of Crocin on Avoidance Memory and Motor Activity Impairment Induced by Doxorubicin Administration in Adult Male Rats

Abstract Background: A lot of studies indicate that cancer chemotherapy drugs such as doxorubicin results in memory impairment. On the other hand, crocin as the chemical constituent isolated from the Saffron is effective on memory and motor enhancement. So, in this work, we have studied the co-administration effect of crocin and doxorubicin on avoidance memory and motor activity in adult male rat. Material and Methods: In this study, 50 male rats were divided into 5 groups: control, sham, doxorubicin, crocin and treated rats with coadministration of doxorubicin and crocin. In crocin group, crocin injected 30mg/kg for 21 days and each rat in the chemotherapy group was treated once a week for 3 weeks with doxorubicin (5mg/kg). Treatment group, received doxorubicin and crocin at the same time. Sham groups administrated with saline. All drugs were injected intraperitoneally. After these procure passive avoidance memory, balance and exploratory behaviors were assessed respectively by shuttle box, rotarod and open field instruments. Results: Memory in rats which have consumed doxorubicin significantly was decreased compared to other groups (p<0.001). Crocin treatment improved memory impairment following doxorubicin injection (p<0.001). Motor activity in open field and rotarod tests in treatment group showed significantly increased compared to doxorubicin group (p<0.001). Conclusion: Crocin consumption beside of anticancer drugs such as doxorubicin has protective effect on the bad effects of chemotherapy drugs on memory and movement

Evaluation the Efficacy of Sodium Valproate and Low Frequency Stimulation During CA1 Hippocampal Kindling on Anxiety-Like Behavior in Adult Male Rat

Background and Aim: Emotional disorders are prevalent in many epileptic patients. So, in this research, we have studied the efficacy of two treatment methods of seizure on anxiety-like behavior during kindling in adult male rat. Materials and Methods: 42 male rats were randomly divided into 6 groups: Control, Sham operation, saline-kindled and drug-kindled groups which have received saline or drug 15 minutes before kindling stimulations, and saline-kindled-LFS or drug-kindled-LFS group which have received saline or drug 15 minutes before kindling stimulations and LFS applied after termination of kindling stimulations. Anxiety-like behavior was assessed on the 6th day by using elevated plus maze and open field apparatus. Findings: kindling significantly increased open arms (OAs) entries percentage, OAs exploration percentage, increasing jumping from elevated plus maze (p<0.001) and rearing frequency in open field apparatus (p<0.05) compared to the sham group. Sodium valproate increased OAs entries percentage and OAs exploration percentage in drug-kindled group compared to sham group (p<0.001). But, there wasn’t any significant difference in jumping from elevated plus maze and rearing in open field compared to sham group. Also, there was no significant change in these parameters in Saline-kindled-LFS, drug-kindled and drug–kindled-LFS groups. Conclusion: Sodium valproate and LFS, as two therapies controlling epilepsy, decrease anxiety induced by kindling stimulation

Interaction of Sodium Valproate With Low-Frequency Electrical Stimulation During Kindlingn

Introduction: The interaction between antiepileptic drugs and brain electrical stimulation is a potential therapy to control seizures in patients with pharmacoresistance to drugs. So, the present study aimed to design to determine the effect of a subeffective dose of sodium valproate combined with low-frequency electrical stimulation during kindling. Methods: One tripolar electrode was implanted stereotactically in the CA1 hippocampus of male Wistar rats. One week after surgery, the rats were kindled by electrical stimulation of hippocampus in a rapid manner (12 stimulations/day) for 6 days with sodium valproate alone or combined with low-frequency electrical stimulation (four packages contained 200 monophasic square wave pulses of 0.1-ms duration at 1 Hz, immediately after kindling stimulations). The duration of afterdischarge, maximum latency to stages 4 and 5, and the maximum duration of these stages were recorded by electromadule during kindling. Results: Application of sodium valproate with low-frequency electrical stimulation caused a reduction in cumulative afterdischarge duration. The maximum latency to the onset of stage 5 seizure increased after sodium valproate application alone, without having a significant effect on the fourth stage. Our findings showed reductions in the seizures duration and increasing in the latency times of both stages after the application of sodium valproate with low-frequency electrical stimulation. Conclusion: It seems that usage of sodium valproate with low-frequency electrical stimulation during kindling was more effective to suppress the epileptic activity than its administration alone and may have a critical role on the antiepileptic effects of sodium valproate

Crocin Treatment after Maternal Hypoxia Attenuates Spatial Memory Impairment and Expression of BACE1 and HIF-1α in Rat Offspring Brain

Objective: Hypoxia via expression of Hypoxia Inducible Factor-1 (HIF-1) is an important and effective factor in the onset and progression of memory disorders such as Alzheimer Disease (AD). The activity of β-secretase (BACE1) increased in hypoxia condition. BACE1 trigger a cascade of pathological events resulting in AD. Crocin act as memory improvement agent but its molecular mechanism is not well-known. So, in this study, the effect of crocin on spatial memory, HIF-1α and BACE1 gene expression were investigated in rat offspring under maternal hypoxia. Materials and methods: Female pregnant rats on the 20th day of pregnancy were divided into 4 groups including: sham, crocin treated, hypoxia and hypoxia group treated with crocin. In hypoxia groups, pregnant rats were exposed to the 7% oxygen and 93% nitrogen intensity for 3 hours. In the crocin treated group, crocin (30 mg/kg) injected at P14-28, (i.p). At the end, Morris water maze was used to assess spatial memory and Real-Time PCR analysis was performed to measure the expression of BACE1 and HIF-1α genes in the brain of offspring. Results: Maternal hypoxia impaired memory task compared to the sham group. But crocin treatment improved cognitive behavior. HIF-1α and BACE1 expression were unregulated in the brain of offspring in hypoxia group. Crocin treatment could attenuate the expression of both genes. Conclusion: According to our results, down- regulation of HIF-1α and BACE1 gene expression in the brain of rat offspring after crocin treatment can be suggested as molecular mechanism for crocin to improve spatial memory

Comparison of high-intensity interval versus low-intensity continuous training for myelin synthesis related genes in C57BL/6 mice

Abstract  Introduction: By increasing the scientific focus on myelination, identifying factors that influence the myelination is an important goal for brain health. There are some studies that regular exercise improves myelin sheath and neuronal regeneration. However, the effects of exercise intensities on the myelination remain unclear. Therefore, the purpose of this study was to compare the effect of high-intensity interval (HIIT) versus low-intensity continuous training (LICT) on myelin synthesis-related genes in hippocampus of C57BL/6 mice. Materials and methods: Male C57BL/6 mice (n = 30) were randomly assigned to 3 groups: control (C), Interval training (IT), and Continuous training (CT). Training programs on the treadmill were performed for 8 weeks and then, the hippocampus of animals was analyzed for the expression of myelin basic protein (MBP) and proteolipid protein (PLP) genes. Data were analyzed using ANOVA. Results: The result showed that HIIT program significantly increased the mRNA levels of MBP and PLP in comparison with LICT and Control groups (P0.05). Conclusion: Our results showed that HIIT had a more efficient by improving the expression of MBP and PLP genes compared to LICT in the hippocampus