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Electron micrograph, granule cell layer, group I, P90. Granule cells (gr), mitochondria (m), rough endoplasmic reticulum (R), lysosome (L), astrocyte (As) (×7,200). Scale bar=2 μm.
Source publication
Epilepsy is one of the most common neurological disorders, its prevalence approximately from 0.5% to 2% of the general population. Generalized seizures could lead to several morphological changes in the brain. This study aimed to investigate the morphological effects of a single convulsive dose of pentylenetetrazol (PTZ) on rat dentate gyrus at dif...
Citations
... Pentylenetetrazol (PTZ) is a drug initially used as circulatory and respiratory stimulant which in high doses led to convulsions, as discovered by a Hungarian American neurologist and psychiatrist [11]. PTZ is an antagonist of gamma aminobutyric acid (GABA) receptors used to induce acute seizures in rodents upon administration of single dose; however, PTZ produces significant pathologic changes or spontaneous epilepsy only when administered repetitively (kindling) [12,13]. Administration of PTZ produces a reliable discriminative stimulus which is mainly mediated by the GABA-A receptor and affects the GABAergic and glutamatergic systems in different regions of the brain, including the hippocampus [14,15]. ...
Objectives
Epilepsy is a neurological disorder resulting from excessive electrical discharge in the brain. Bombax costatum (BC) is an herb being used in African traditional medicine for the treatment of seizures. This study evaluated the possible anti-convulsant potential of stem bark ethanolic extract of BC on PTZ-induced kindling in rats.
Methods
Thirty-five Wistar rats were grouped into five ( n = 7) and received normal saline, 35 mg/kg of PTZ, 5 mg/kg diazepam followed by 35 mg/kg PTZ after 30 min and BC stem back ethanolic extract at 125 mg/kg and 250 mg/kg followed by 35 mg/kg of PTZ intraperitoneally after 30 min. BC was administered orally daily while normal saline and PTZ were given intraperitoneally every other day for 26 days. Seizure activity was evaluated using the Racine scale, cognitive abilities through modified elevated plus maze and anxiety through forced swimming test. Further, the levels of GABA and oxidative stress biomarkers were also evaluated from the rat’s brain homogenate.
Results
Pretreatment with BC significantly reduced ( p < .05) the seizure score and increased GABA level in BC treated rats when compared to PTZ alone treated rats. The first transfer latency of PTZ alone treated rats was significantly increased ( p < .05) relative to the control rats and rats pretreated with diazepam and BC extract. Pretreatment with BC extract at 250 mg/kg was shown to significantly increase ( p < .05) the activities of catalase, reduced glutathione, and superoxide dismutase compared to the PTZ alone treated rats.
Conclusions
Conclusively, BC was found to prevent seizure, avert neurodegeneration, and enhance cognition in PTZ-treated rats by regulating GABA level and enhancing antioxidant activity. Therefore, BC could be explored further for possible development of antiseizure agents.
... Epilepsy is a widespread neurological condition that impacts around 1% of the global population, with a significantly greater occurrence in poorer nations [1]. Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes [2]. ...
Background: Epilepsy is defined by an excessive level of activity in the neurons and coordinated bursts of electrical activity, resulting in the occurrence of seizure episodes. The precise cause of epileptogenesis remains uncertain; nevertheless, the etiology of epilepsy may involve neuroinflammation, oxidative stress, and malfunction of the neurotransmitter system. Objective: The goal of this investigation was to assess barbaloin’s protective properties with respect to pentylenetetrazol (PTZ)-)-induced cognitive deficits in rats via antioxidative, anti-inflammatory, and neurotransmitter-modulating effects. Methods: Wistar rats were subjected to PTZ [40 mg/kg (i.p.)], which induced cognitive decline. Behavior assessment using a kindling score, open-field test (OFT), novel object recognition test (NORT), and assays for superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), malondialdehyde (MDA), acetylcholinesterase (AChE), caspase-3, nitric oxide (NO), interleukins-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, nuclear factor kappa-B (NF-κB), Bcl-2 and Bax, and neurotransmitter levels [GABA, DA, NE, and serotonin (5-HT)] were performed. Results: The treatment of rats with barbaloin resulted in behavior improvement and significant changes in the levels of GSH, SOD, CAT, MDA, AChE, NO, IL-6, IL-1β, TNF-α, NF-κB, caspase-3, Bcl-2, and Bax compared to the PTZ control group. Barbaloin treatment resulted in notable changes in neurotransmitter levels (GABA, NE, 5-HT, DA) compared to the PTZ group. Conclusions: The ongoing study has gathered evidence indicating that the injection of barbaloin has resulted in significant improvements in cognitive performance in rats. This is achieved by inhibiting oxidative stress, enhancing the activity of natural antioxidant enzymes, reducing cytokine levels, and increasing the levels of neurotransmitters in the brain. These results were detected in comparison to a PTZ control and can be attributed to the potent anti-inflammatory and antioxidant capabilities of barbaloin, which could be linked to its neuroprotective properties. Barbaloin may potentially increase cognitive decline and boost neuronal survival by altering the expression of Bax, caspase-3, Bcl-2.
... The seizure outcomes in young and adult animals are also different. In adult animals, a single episode of PTZ-induced seizures usually does not result in significant neuronal loss in the brain [2,16]; however, it can cause the rapid emergence of dark neurons [17,18], 2 of 18 an increase in the number of proliferating cells in the dentate gyrus and the subventricular zone [16], ultrastructural changes in some neurons, glial cells, and synapses in the CA1 field of the hippocampus [19]. Subsequently, one episode of PTZ-induced seizures in adult (two-month-old) male Wistar rats is accompanied by slowly developing cognitive decline [20]. ...
... PTZ-induced seizures in 10-day-old (P10) rats resulted in significant neuronal death in the dentate gyrus, whereas neuronal loss did not reach a statistically significant level at P21 [18]. In animals receiving PTZ at P18, another research group revealed cell loss only in the CA3 area of the hippocampus and in the hilus of the dentate gyrus, while in the CA1 area of the hippocampus, the dentate gyrus remained intact [21]. ...
Data on the long-term consequences of a single episode of generalized seizures in infants are inconsistent. In this study, we examined the effects of pentylenetetrazole-induced generalized seizures in three-week-old rats. One month after the seizures, we detected a moderate neuronal loss in several hippocampal regions: CA1, CA3, and hilus, but not in the dentate gyrus. In addition, long-term synaptic potentiation (LTP) was impaired. We also found that the mechanism of plasticity induction was altered: additional activation of metabotropic glutamate receptors (mGluR1) is required for LTP induction in experimental rats. This disturbance of the plasticity induction mechanism is likely due to the greater involvement of perisynaptic NMDA receptors compared to receptors located in the core part of the postsynaptic density. This hypothesis is supported by experiments with selective blockades of core-located NMDA receptors by the use-dependent blocker MK-801. MK-801 had no effect on LTP induction in experimental rats and suppressed LTP in control animals. The weakening of the function of core-located NMDA receptors may be due to the disturbed clearance of glutamate from the synaptic cleft since the distribution of the astrocytic glutamate transporter EAAT2 in experimental animals was found to be altered.
... Epilepsy is a common neurological disease that influences approximately 1% of humans worldwide with a much higher incidence in developing countries (Mohamed and Eltony 2020). Clinically, it is a dynamic and chronic disorder of abnormal neuronal electrical activity, characterized by recurrent unprovoked seizures through an imbalance between excitability and inhibition in the brain which may either affect specific brain systems or originate in a restricted area and spread to involve multiple cortical and subcortical circuits (Akyuz et al. 2020;Wu et al. 2020). ...
... Pentylenetetrazol (PTZ), a γ-aminobutyric acid (GABA) ergic receptor antagonist, has a stimulant epileptogenic property and is commonly used as a convulsing drug in experimental studies. A tonic-clonic seizure was developed by a single or repeated injection of PTZ which causes cognitive deficit and a gradual decrease in short-term memory function (Mohamed and Eltony 2020). ...
... GbE and LC are well studied as antioxidant compounds in different experimental models. However, many reports have discussed the neuroprotective effect of GbE against brain-induced toxicity (Mohamed et al. 2020), and others illustrated the defensive role of LC in induced neuroinflammation and neurodegeneration models (Hussein et al. 2018), but there is no documented work on the effect of their combination. The neuroprotective and therapeutic effects of GbE and LC could be mediated via their antioxidant properties by directly scavenging ROS, decreasing lipid peroxidation, increasing the antioxidant system, or indirectly preventing free radical production, mitochondrial dysfunction, and AchE is one of the brain's highly active enzymes that is widely expressed in different brain regions and has several functions. ...
Epilepsy is one of the most common serious brain disorders, affecting about 1% of the population all over the world. Ginkgo biloba extract (GbE) and L-carnitine (LC) reportedly possess the antioxidative activity and neuroprotective potential. In this report, we investigated the possible protective and therapeutic effects of GbE and LC against pentylenetetrazol (PTZ)-induced epileptic seizures in rat hippocampus and hypothalamus. Adult male albino rats were equally divided into eight groups: control, GbE (100 mg/kg), LC (300 mg/kg), PTZ (40 mg/kg), protective groups (GbE + PTZ and LC + PTZ), and therapeutic groups (PTZ + GbE and PTZ + LC). The oxidative stress, antioxidant, and neurochemical parameters, viz., malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), acetylcholine esterase (AchE), dopamine (DA), norepinephrine (NE), and serotonin (5-HT), in the hippocampal and hypothalamic regions have been evaluated. PTZ injection leads to an increase in the seizure score, the levels of MDA and NO, and to a decrease in the activity of GSH, SOD, CAT, and GPx. Besides, monoamine neurotransmitters, DA, NE, and 5-HT, were depleted in PTZ-kindled rats. Furthermore, PTZ administration caused a significant elevation in the activity of AchE. Hippocampal and hypothalamic sections from PTZ-treated animals were characterized by severe histopathological alterations and, intensely, increased the ezrin immunolabeled astrocytes. Pre- and post-treatment of PTZ rats with GbE and LC suppressed the kindling acquisition process and remarkably alleviated all the aforementioned PTZ-induced effects. GbE and LC have potent protective and therapeutic effects against PTZ-induced kindling seizures via the amelioration of oxidative/antioxidative imbalance, neuromodulatory, and antiepileptic actions.
... It was possible to verify that DEXA acts in reducing not only the intensity of seizures, but also the onset time for seizures, reinforcing the possible anticonvulsant and neuroprotective role of this drug. 7 As for OS, no group differed from the control groups (vehicle and diazepam) in relation to TBARS levels; however, an increase in lipid peroxidation was found in the DEXA group 4 mg/kg compared to the DEXA 2 mg/kg group. The SOD enzyme catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide and because of this, it is an important antioxidant defense. ...
Background and purpose:
Oxidative stress (OS) is defined as an excessive production of reactive oxygen species that cannot be neutralized by the action of antioxidants, but also as an alteration of the cellular redox balance. The relationship between OS and epilepsy is not yet fully understood. The objective of this study was to evaluate the effect of dexamethasone on OS levels and memory in the kindling model induced by pentylenetetrazole.
Methods:
The animals were divided in six groups: control group that received no treatment, vehicle group treated with vehicle, diazepam group, and groups treated with dexamethasone (1, 2 and 4 mg/kg). Treated animals received pentylenetetrazole in alternated days for 15 days. Inhibitory avoidance test was conducted in 2 hours and OS was evaluated after animal sacrifice.
Results:
Regarding the treatment with dexamethasone, there was no significant difference when compared to the control groups in relation to the inhibitory avoidance test. On OS levels, there was a decrease in catalase activity levels in the hippocampus and an increase in thiobarbituric acid reactive substances and glutathione peroxidase levels in the hippocampus.
Conclusions:
The anticonvulsant effect of dexametasone remains uncertain. Immunological mechanisms, with the release of cytokines and inflammatory mediators, seem to be the key to this process. The mechanisms that generate OS are probably related to the anticonvulsant effects found.
... Temporal lobe epilepsy (TLE) is a clinically prevalent type of partial epilepsy. Severe head injury, stroke, intracranial infections, brain tumors, or preceding status epilepticus (SE) are factors that can induce functional and chemical changes in the brain and development of epilepsy [2][3][4][5]. Due to alterations occurring during epileptogenesis, patients tend to develop various comorbidities such as cognitive and psychiatric disorders, which have a detrimental impact on their quality of life [6]. ...
Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities.
... In response to neuronal degeneration and loss, the astrocytes increased in an attempt to limit the oxidative damage and inflammation [30,31]. Mohamed and Eltony [32] revealed that the advanced astrogliosis might be a protective morphological change. ...
Previous studies have shown that cypermethrin (CYP), a broad spectrum pesticide has a teratogenic effect on rat offspring born to an exposed dam with no information on its effect on the development of the brain. To the best of our knowledge, this research is the first attempt to study the postnatal development medulla oblongata of rat offspring exposed to CYP during the perinatal period and the possible neuroprotective role of melatonin. The offspring of treated female rats were organized into control, melatonin (1 mg/kg/day orally); CYP (12 mg/kg/day orally); and CYP/melatonin groups. The mothers received treatments from day 6 of gestation until day 21 after birth. At Postnatal days 7 and 21, the animals were sacrificed and their medulla oblongata was removed and subjected to histological, immunohistochemical, and electron microscopic studies. CYP induced neuronal degeneration by chromatolysis and pyknosis. Nuclear changes, cytoplasmic vacuolation, damage mitochondria, and breakdown of RER were also detected. Reduction of microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), and oligodendrocyte transcription factor expressions and increment of glial fibrillary acidic protein expression in the medulla oblongata of the developing rats were observed. On the other hand, melatonin led to an obvious improvement of the injured medulla oblongata tissues and ameliorating the damaging effects of CYP. In conclusion, melatonin has protected rats against CYP-induced histopathological and immunohistochemical changes. This may be due to the protection of MAP-2, conservation of MBP, an increment of oligodendrocytes, and alleviation of astrogliosis.
The aim of this study was to understand the expression of big potassium (BK, KCa1.1) channels in epileptic seizures under magnetic field application. Forty Wistar albino adult male rats were divided into five groups (n = 8). First group rats were control group. Pentylenetetrazole (PTZ) administrated to second group rats to induce the seizures with 35 mg/kg intraperitoneally injection every two days. Levetiracetam (LEV) i.p. at a dose of 108 mg/kg was given to third group rats as positive control group (PC) before 20 minutes PTZ administration. Pulsed magnetic field with 1.5 mT was exposed to the fourth group rats for 3 hours a day for 1 month as magnetic field (MF) group. 1.5 mT pulsed magnetic field was exposed to the fifth group rats for 3 hours a day for 1 month in addition to PTZ administration (PTZ+MF). KCa1.1 not changed in hippocampus of PTZ rats while increased in frontal cortex and pons for PTZ group but not changed with magnetic field exposure. KCa1.1 increased in heart of PTZ animals and turned back to mean control values with magnetic field exposure. Suppressing the expected increase of c-fos protein expression in seizures with magnetic field application but not being able to change the KCa1.1 expression shows that new studies can be done by increasing the frequency of 1.5 mT magnetic field.
Background
Epilepsy is a prevalent neurological disorder that significantly reduces the patient's quality of life. The present study aims to evaluate whether dental pulp stem cells (DPSCs) transplant effectively decreases inflammation and cell death in the brain cells to reduce seizure damage.
Methods
A seizure was induced in rats using intraperitoneal injections of pentylenetetrazole (PTZ). In the PTZ + DPSC group, bilateral hippocampal transplantation of DPSCs in PTZ-lesioned rat models was conducted. After one-month, post-graft analysis was performed, and some behavioral factors, such as working memory and long-term memory, were measured using a T-maze test and passive avoidance test, respectively. We investigated the immunohistopathology and distribution of astrocyte cells through light microscopy and Sholl analysis, respectively. Also, the Voronoi tessellation method was employed to estimate the spatial distribution of the cells in the hippocampus.
Results
For improving the behavioral aspects of rats with induced seizures, a reduction in astrogliosis, astrocytes process length, the number of branches, and intersections distal to the soma was observed in their hippocampus compared to the control group. More analysis indicated that the grafted DPSCs decreased the caspase-3 expression in the hippocampus of rats with induced seizures. Moreover, the DPSCs transplant protected hippocampal pyramidal neurons against PTZ toxicity and improved the spatial distribution of the hippocampal neurons.
Conclusions
Our findings suggested that DPSCs transplant can be a potent modifier of astrocytes' reactivation and inflammatory responses.
Aims:
To investigate the effects of different doses of esculetin on epileptiform activity, behavioral seizures, memory impairment, and cortical and hippocampal NF-κB, as a mediator of pro-inflammatory gene induction, and pro-inflammatory cytokines in penicillin- and pentylenetetrazole(PTZ)-induced seizure models in rats.
Main methods:
Different doses of esculetin (5, 10, and 20 mg/kg), and diazepam (5 mg/kg) as a positive control, were tested in penicillin- and pentylenetetrazole(PTZ)-induced seizure models. In the PTZ model, cognitive function, behavioral seizures, and cortical and hippocampal pro-inflammatory biomarkers and survival factor was evaluated. In the penicillin model, the frequency and amplitude of electrophysiological epileptiform activity were assessed.
Key findings:
In the PTZ model, the 10 mg/kg esculetin displayed anticonvulsant effects by extending onset-times of myoclonic-jerk and generalized tonic-clonic seizure, and by diminishing seizure severity and duration of generalized tonic-clonic seizure. It also ameliorated PTZ-induced cognitive impairment, and cortical and hippocampal activin-A, IL-1β, IL-6 and NF-κB levels. In the penicillin model, the 10 mg/kg esculetin decreased the frequency of spikes without changing the amplitude of spikes. As a positive-control, diazepam reversed all changes induced by both PTZ and penicillin.
Significance:
Esculetin exhibits anticonvulsant and memory-improving effects by alleviating the behavioral and electrophysiological characteristics of epileptic seizures. Additionally, esculetin exerts anti-neuroinflammatory actions in the PTZ-induced seizures model. Thus, esculetin may be a multi-targeted promising agent with anticonvulsant and anti-neuroinflammatory effects in the treatment of epilepsy.
