The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats

Borham, Layla E.; Mahfoz, Amal M.; Ibrahim, Ibrahim A.; Shahzad, Naiyer; ALrefai, Abeer Ahmed; Labib, Amira; Sef, Bassam Bin; Alshareef, Abdulrahmman; Khan, M. Nasiruddin; Milibary, Ali; Ghamdi, Saeed Al

doi:10.1016/j.brainres.2016.07.046

Cited by 24 publications

(11 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IFN-γ plays an important role in the development of the brain’s excitatory seizure pathways, and it has been associated with the development of limbic seizures (Borham et al., 2016). IFN-γ has been implicated in the seizure generation; this makes IFN-γ worth exploring in the current investigation.…”

Section: Discussionmentioning

confidence: 99%

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

et al. 2019

View full text Add to dashboard Cite

Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.

show abstract

Section: Discussionmentioning

confidence: 99%

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Numerous studies have focused on the effects of glucocorticoids in epilepsy and convulsions, but the conclusions are controversial so far [11,12,[28][29][30][31][32][33]. Different dosages, courses, and time points of glucocorticoid administration might be responsible for these discrepancies.…”

Section: Discussionmentioning

confidence: 99%

“…Glucocorticoids have proven to be helpful in treatment of epilepsy in numerous clinical and experimental studies [8][9][10][11][12]. Glucocorticoids have two type of receptors in vivo: mineralocorticoid receptors (MRs) of high affinity and glucocorticoid receptors (GRs) of low affinity [13].…”

Section: Ivyspringmentioning

confidence: 99%

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

et al. 2020

View full text Add to dashboard Cite

The filamentous actin (F-actin) cytoskeleton is progressively damaged after status epilepticus (SE), which is related to delayed neuronal death, aberrant recurrent circuits and epileptogenesis. Glucocorticoids regulate dendritic spine remodeling by acting on glucocorticoid receptors and the dynamics of the F-actin cytoskeleton. Our previous study showed that administration of dexamethasone (DEX) in the latent period of the pilocarpine epileptic model reduces damage to the hippocampal filamentous actin cytoskeleton and the loss of hippocampal neurons and aids in maintaining the synaptic structures, but it is not sufficient to stop epileptogenesis. In this work, we focused on the role of glucocorticoids in regulating the hippocampal F-actin cytoskeleton during SE. We examined the abundance of synaptic F-actin, analyzed the hippocampal F-actin/G-actin (F/G) ratio and pCofilin, and evaluated the number of hippocampal neurons and pre/postsynaptic markers in pilocarpine-induced status epilepticus mice with or without administration of dexamethasone (DEX). We found that the latency of Stage 3 seizures increased, the mortality decreased, the damage to the synaptic F-actin cytoskeleton in the hippocampal subfields was significantly attenuated, and a greater number of postsynaptic structures were retained in the hippocampal subfields after treatment with DEX. These results indicate that treatment with dexamethasone stabilizes the synaptic F-actin cytoskeleton and reduces the damage to the brain due to SE. This approach is expected to be beneficial in alleviating delayed neuron damage and the process of epileptogenesis.

show abstract

“…After 30 min, they received PILO (380 mg/kg I.P.) [44]. Group 6 (PILO+LPS+VPA+Celecoxib) animals received celecoxib (10 mg/kg I.P.)…”

Section: Experimental Designmentioning

confidence: 99%

Celecoxib Decrease Seizures Susceptibility in a Rat Model of Inflammation by Inhibiting HMGB1 Translocation

et al. 2021

View full text Add to dashboard Cite

The risk of developing epilepsy is strongly linked to peripheral inflammatory disorders in humans. High-mobility group box protein 1 (HMGB1) has the most focus for being a suspect in this scenario. The current study aimed to detect the celecoxib effect, an anti-inflammatory drug, on decreasing seizure susceptibility and organ damage in lipopolysaccharides (LPS)/pilocarpine (PILO) pretreated Wistar rats. Rats were divided into 6 groups (8 each): group 1 (control), group 2 (PILO), group 3 (PILO+LPS), group 4 (PILO+LPS+(VPA) Valproic acid), group 5 (PILO+LPS+Celecoxib), and group 6 (PILO+LPS+VPA+Celecoxib). LPS was used to induce sepsis and PILO to induce seizures. Oxidative stress markers, pro-inflammatory cytokines, and HMGB1 levels in serum and brain homogenate were evaluated. Histopathological studies were conducted on the hippocampus, liver, lung, and kidney. Treatment with celecoxib either alone or in combination with VPA significantly reduced Racine score and delays latency to generalized tonic-clonic seizures onset with a significant decrease in hippocampal levels of pro-inflammatory cytokines, oxidative stress markers, and increase in reduced glutathione. In addition, celecoxib treatment either alone or in combination with VPA suppressed HMGB1translocation into peripheral circulation more than treatment with VPA alone. Furthermore, hippocampus, liver, lung, and kidney histopathological changes were improved in contrast to other epileptic groups. Celecoxib either alone or combined with VPA has antiepileptic and multiorgan protective effects on acute seizures and inflammatory models induced by PILO with LPS. It decreased histopathological findings, oxidative, and inflammatory effects induced by VPA and LPS. This might be due to its anti-oxidative, anti-inflammatory and anti-HMGB1 mediated effects.

show abstract

The effect of some immunomodulatory and anti-inflammatory drugs on Li-pilocarpine-induced epileptic disorders in Wistar rats

Cited by 24 publications

References 53 publications

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model

Effects of Dexamethasone on Remodeling of the Hippocampal Synaptic Filamentous Actin Cytoskeleton in a Model of Pilocarpine-induced Status Epilepticus

Celecoxib Decrease Seizures Susceptibility in a Rat Model of Inflammation by Inhibiting HMGB1 Translocation

Contact Info

Product

Resources

About