CBD treatment decreases cell injury in the hippocampal area of A. Hyperplasia of astrocytes in the hippocampus of CBD-treated rats was. Agmatine treatment decreases cell injury in the hippocampal area of area of pentylenetetrazole-treated rats, hippocampal pyramidal cells. CBD treatment did not affect the expression of iNOS in the hippocampus; in rats, decreased the astrocytic hyperplasia, decreased neuronal damage in the . in ADC in the subiculum of CBD-treated mice compared with the untreated group. . . the neuronal loss and astrocyte hyper- plasia in the hippocampus region.
decreases of in hippocampal CBD area injury pentylenetetrazole-treated cell rats treatment the
Decreased neuronal injury in the hippocampal region of agmatine-treated rats. To investigate how agmatine treatment affects astrocytic hyperplasia, hematoxylin and eosin staining and image analysis were performed Fig. By contrast, in the model control group, GFAP-positive cells were significantly increased in number and exhibited more intense staining, as well as thicker and extended neurites.
In the agmatine groups, GFAP expression was increased to a certain extent, however, the number of GFAP-positive cells was reduced and the staining was less intense compared with the model control group.
The cells were decreased in size and the neurites were relatively thinner and shorter. These results demonstrated that agmatine suppressed astrocytic hyperplasia.
A Hyperplasia of astrocytes in the hippocampus of agmatine-treated rats was reduced. Immunostaining of GFAP was performed on the sections to detect increased astrocyte expression.
In addition, no significant difference in NR2b mRNA expression was observed among all the groups data not shown. These results indicated that treatment with higher concentrations of agmatine decreased the expression of the NMDA receptor. In the present study, it was demonstrated that consecutive administration of agmatine provided protection against pentylenetetrazole-induced chronic seizures in rats. These results are consistent with previous studies that demonstrated the inhibitory effect of agmatine in acute seizure animal models 2 , 3.
Furthermore, in the present study, rats treated with agmatine exhibited significantly reduced astrocytic hyperplasia and neurological defects in the hippocampal area compared with rats in the model control group. Furthermore, the expression of the NMDA1 receptor was selectively suppressed in agmatine-treated rats.
The results from the present study are in accordance with several previous studies demonstrating that high doses of agmatine had marked anticonvulsive effects 3 — 5. This may be due to the rapid metabolism of agmatine in the peripheral tissues. In addition, the blood-brain barrier may also restrict the penetration of agmatine into the brain 6.
Therefore, an adequate peripheral dose is required to produce apparent protective effects. In fact, in the present study repeated administration of agmatine did not decrease the kindling rate.
This suggests that agmatine is unable to alter the threshold and this may be associated with under-dosing, which requires investigation in future studies. Astrocytes are important glial cells in the brain.
Following epilepsy, the number of astrocytes increases and alterations in morphology and function are observed. Astrocytes have been demonstrated to be important in the mechanisms underlying epilepsy For example, it has been demonstrated that they are involved in the maintenance of the inflammatory state during epilepsy by releasing inflammatory cytokines.
These cytokines directly alter the excitability of the neurons and promote mossy fiber budding of the dentate gyrus to form an excitability loop, which may induce seizures In the present study, GFAP immunohistochemistry demonstrated that agmatine was able to significantly reduce hippocampal astrocytic cell proliferation in a dose-dependent manner following pentylenetetrazole-induced seizures. This may contribute to the inhibitory effect of agmatine on seizures.
The activation of NMDA receptors is responsible for the development of seizures and their binding sites are upregulated in different types of convulsant animal models. NMDA receptor antagonists have previously been demonstrated to inhibit convulsion In addition, agmatine has been shown to selectively modulate NMDA subunits in rat hippocampal neurons 12 and mediate anticonvulsive actions 3 , 4.
However, this was only observed in animals repeatedly treated with large doses of agmatine. Seizures are known to cause neuronal death and cell loss may in turn increase the potential for further seizure activity. This feedback cycle may explain the progressive and chronic course of epilepsy Previous studies have revealed a decrease in the number of hippocampal neurons in seizures induced by pentylenetetrazole In the present study, the results of hippocampal morphology suggest that agmatine may decrease cell loss in the rat hippocampus.
Agmatine exhibits seizure-suppressive and neuroprotective capabilities and may therefore protect against convulsions on seizure-suppressive and neuroprotective capabilities. Several studies have also suggested that the inhibitory effect of agmatine may be important in its anticonvulsive properties 2 , 6.
In the present study, the expression of iNOS was found to increase in the hippocampus following pentylenetetrazole administration. However, agmatine was not found to significantly inhibit iNOS expression.
Agmatine treatment results in decreased astrocytic hyperplasia, neuronal cell loss and selective suppression of the NMDA1 receptor in the hippocampus.
The majority of clinical epilepsy cases are diagnosed as long-term repeated chronic epilepsy. Thus, further investigation regarding the function of agmatine in chronic epilepsy is particularly important. National Center for Biotechnology Information , U. Published online May Author information Article notes Copyright and License information Disclaimer. Received Dec 4; Accepted Mar The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
This article has been cited by other articles in PMC. Abstract The aim of the present study was to investigate the mechanism underlying the effects of different doses of agmatine in rats with chronic epilepsy. Introduction Agmatine is an endogenous amine synthesized via the decarboxylation of L-arginine mediated by arginine decarboxylase.
Behavioral observations of convulsion The behavior of each rat was observed for 1 h after pentylenetetrazole injection.
Sample preparation After the rats were decapitated, the entire brain was rapidly removed and dissected on ice.
Hematoxylin and eosin staining Two paraffin slices were selected and stained using hematoxylin and eosin as previously described 9. Results Agmatine treatment reduces the severity of pentylenetetrazole-induced chronic seizures To evaluate the effect of agmatine on chronic seizures induced by pentylenetetrazole, convulsions were measured using a five-point scale, as previously described by Fathollahi et al 8.
Open in a separate window. Table I Severity and the kindling rate of rats in each treatment group. Agmatine treatment decreases cell injury in the hippocampal area of pentylenetetrazole-treated rats To determine whether agmatine alleviated cell injury in the hippocampal area of pentylenetetrazole-treated rats, hippocampal pyramidal cells were observed under a microscope. Treatment with agmatine suppresses astrocytic hyperplasia To investigate how agmatine treatment affects astrocytic hyperplasia, hematoxylin and eosin staining and image analysis were performed Fig.
Discussion In the present study, it was demonstrated that consecutive administration of agmatine provided protection against pentylenetetrazole-induced chronic seizures in rats. Biological significance of agmatine, an endogenous ligand at imidazoline binding sites. Agmatine exerts anticonvulsant effect in mice: Abdel-Salam 1 , Amany A.
Khadrawy 3 and Fatma A. The effect of Cannabis sativa extract on chemical kindling induced in rats by the repeated intraperitoneal ip injections of pentylenetetrazole PTZ was studied.
Seizures were recorded for 20 minutes. Control rats received ip saline. Cannabis treatment caused significant elevation of mean seizure score as compared to PTZ only group after the 5th, 6th and 7th PTZ repeated injections during seizure development.
In particular, cannabis caused significant elevation in the frequency of myoclonic jerks, rearing stage 3 , turn over onto one side position and back position stage 4 , and generalized tonic-clonic seizures stage 5 compared with the PTZ only group. PTZ caused significant elevations in brain lipid peroxidation malondialdehyde , and nitric oxide along with deceased reduced glutathione level.
In addition, brain acetylcholinesterase AChE activity significantly decreased compared to control value after PTZ treatment. Reduced glutathione level was restored by cannabis. Histopathological studies indicated the presence of spongiform changes, degenerated and necrotic neurons, inflammatory cells, and gliosis in cerebral cortex and degeneration of some Purkinje cells in the cerebellum in both PTZ- and cannabis-PTZ-treated groups.
It is concluded that in an epilepsy model induced by repeated PTZ administration, cannabis increased lipid peroxidation and mean seizure score. Biomed Pharmacol J ;11 3. Cannabis sativa is well known for its recreational uses. Only recently, cannabis and cannabinoid-based medicines have come to attention as a remedy for different medical conditions.
The brain tissue is vulnerable to oxidative damage. Meanwhile, the brain is rich in polyunsaturated fatty acids, the target of these reactive species. On the other hand, there are limited antioxidant mechanisms compared with other organs. In this study, the effect of Cannabis sativa extract was examined on brain oxidative stress and epileptic seizures induced by the repeated administration of pentylenetetrazole PTZ in rats.
The study was conducted on male Sprague-Dawley rats weighing g. Rats were group-housed under temperature- and light-controlled conditions and allowed standard laboratory rodent chow and water ad libitum. Seven to eight rats were used per group. Cannabis sativa resin hashish was kindly provided by the Ministry of Justice of Egypt. Extract of Cannabis sativa. The method of extraction was that described by Turner and Mahlberg 36 with modification.
Louis, USA every 48 hours. After each PTZ treatment, rats were placed separately under glass funnels, and the appearance of clonic and tonic seizures were recorded during individual observations for 20 minutes.
The resultant seizures were classified according to the following scale Rats were randomly divided into three groups rats each. Rats were treated with 0. Two hour after the last PTZ injection, rats were quickly euthanized by decapitation; their brains removed on ice cold glass plate, stored at C until the biochemical assays. Malondialdehyde MDA , a product of lipid peroxidation was determined in tissue homogenates according to the method of Nair and Turne. Reduced glutathione GSH was determined in tissue homogenates using the procedure of Ellman et al.
Nitric oxide was determined using colorimetric assay where nitrate is converted to nitrite via nitrate reductase. Griess reagent then act to convert nitrite to a deep purple azo compound that can be determined using spectrophotometer. The procedure used was a modification of the method of Ellmanet al. The color was read immediately at nm. A probability value of less than 0.
Rats treated with PTZ exhibited significantly higher malondialdehyde In addition, brain reduced glutathione significantly decreased by Click here to View figure.
Mechanism of gastrodin in cell apoptosis in rat hippocampus tissue induced by desflurane
On each day following baicalein treatment, behavioural alterations in the rats Results: Analyses of behavioural changes revealed significant (p decrease in alterations in cell morphology, and also inhibited pentylenetetrazole-induced . mg/kg and 50 mg/kg doses of baicalein on hippocampal neuronal injury in. We also investigated whether in vivo treatment with CBD altered the fate of CCK in acute brain slices of rat temporal lobe epilepsy in in vivo (induced by . a drug would decrease the excitation of interneurons or pyramidal cells; . onto postsynaptic pyramidal cells in the CA1 region of the hippocampus. tionated cell culture supernatant derived from hippocampal of neural regeneration peptide on pentylenetetrazol-induced seizures in rats, Neuropeptides.