Neuroinflammation in Pathogenesis of Audiogenic Epilepsy: Altered Proinflammatory Cytokine Levels in the Rats of Krushinsky–Molodkina Seizure-Prone Strain

Сурина, Н. М.; Федотова, И. Б.; Nikolaev, G. S.; Греченко, В.В.; Gankovskaya, L.V.; Ogurtsova, Anastasia D; Полетаева, И. И.

doi:10.1134/s0006297923040041

Cited by 5 publications

(5 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…At the same time, the observed hypolocomotion was in line with that reported for a maternal immune activation model of ASD [ 57 ]. Remarkably, profound neuroinflammation also plays a role in the pathogenesis of audiogenic epilepsy in KM rats, since a number of pro-inflammatory cytokines were affected by sound exposure in KM rats [ 22 ]. It is interesting to check whether hypolocomotion would be seen in other animal models of neuroinflammation-associated ASD.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, we reported social contact deficits in rats of Krushinsky–Molodkina (KM) strain [ 17 ]. This Wistar-derived inbred [ 18 ] strain has been used as a model for human temporal lobe epilepsy and vascular pathology from the late 1940s [ 19 ] to currently [ 20 , 21 , 22 , 23 ]. All KM rats are susceptible to audiogenic seizures (AGS) of the maximal score, in response to sound provocations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats

Rebik,

Broshevitskaya,

Kuzhuget

et al. 2023

Biomedicines

View full text Add to dashboard Cite

Epilepsy or epileptic syndromes affect more than 70 million people, often comorbid with autism spectrum disorders (ASD). Seizures are concerned as a factor for social regression in ASD. A stepwise experimental approach to this problem requires an animal model to provoke seizures and monitor subsequent behavior. We used rats of the Krushinsky–Molodkina (KM) strain as a validated inbred genetic model for human temporal lobe epilepsy, with recently described social deficiency and hypolocomotion. Generalized tonic-clonic seizures in KM rats are sound-triggered, thus being controlled events in drug-naïve animals. We studied whether seizure experience would aggravate contact deficits in these animals. Locomotor and contact parameters were registered in “the elevated plus maze”, “socially enriched open field”, and “social novelty/social preference tests” before and after sound-provoked seizures. The triple seizure provocations minimally affected the contact behavior. The lack of social drive in KM rats was not accompanied by a submissive phenotype, as tested in “the tube dominance test”, but featured with a poor contact repertoire. Here, we confirmed our previous findings on social deficits in KM rats. The contact deficiency was dissociated from hypolocomotion and anxiety and did not correlate with seizure experience. It was established that experience of rare, generalized tonic-clonic convulsions did not lead to an impending regress in contact motivation, as seen in an animal model of genetic epilepsy and comorbid social deficiency. One of the oldest animal models for epilepsy has a translational potential to study mechanisms of social behavioral deficits in future neurophysiological and pharmacological research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats

Rebik,

Broshevitskaya,

Kuzhuget

et al. 2023

Biomedicines

View full text Add to dashboard Cite

show abstract

“…Neuroinflammation, involving histaminergic steps, would be a putative candidate for triggering such a multi-step diffuse lowering of the cortical aminergic tone. It is reported that proinflammatory cytokines are involved in the pathogenesis of audiogenic epilepsy in KM rats [103], and absence epilepsy in WAG/Rij rats [104][105][106].…”

Section: Effects Of Generalized Epilepsiesmentioning

confidence: 99%

D1-Like and D2-Like Dopamine Receptors in the Rat Prefrontal Cortex: Impacts of Genetic Generalized Epilepsies and Social Behavioral Deficits

Birioukova,

van Luijtelaar,

Midzyanovskaya

2024

Receptors

View full text Add to dashboard Cite

The involvement of the prefrontal cortical dopaminergic system in the psychopathology of epilepsies and comorbid conditions such as autism spectrum disorder (ASD) still needs to be explored. We used autoradiography to study the D1-like (D1DR) and D2-like (D2DR) receptor binding density in the prefrontal cortex of normal Wistar rats and Wistar-derived strains with generalized convulsive and/or non-convulsive epilepsy. WAG/Rij rats served as a model for non-convulsive absence epilepsy, WAG/Rij-AGS as a model of mixed convulsive/non-convulsive form, and KM strain was a model for convulsive epilepsy comorbid with an ASD-like behavioral phenotype. The prefrontal cortex of rats with any epileptic pathology studied demonstrated profound decreases in binding densities to both D1DR and D2DR; the effects were localized in the primary and secondary anterior cingulate cortices, and adjacent regions. The local decreased D1DR and D2DR binding densities were independent of (not correlated with) each other. The particular group of epileptic rats with an ASD-like phenotype (KM strain) displayed changes in the lateral prefrontal cortex: D1DR were lowered, whereas D2DR were elevated, in the dysgranular insular cortex and adjacent regions. Thus, epilepsy-related changes in the dopaminergic system of the rat archeocortex were localized in the medial prefrontal regions, whereas ASD-related changes were seen in the lateral prefrontal aspects. The findings point to putative local dopaminergic dysfunctions, associated with generalized epilepsies and/or ASD.

show abstract

“…If for some reason the inflammatory response goes excessively uncontrolled or persists over time, it causes pathological neuroinflammation, which increases blood-cerebrospinal fluid barrier permeability and peripheral immune cell infiltration, and elevated levels of classical inflammatory cytokines, leading to cell death and histopathological damage [ 1 , 4 ]. Neuroinflammation plays a central role in many complex health problems, such as neurodegenerative diseases [ 5 , 6 ], autoimmune diseases (e.g., multiple sclerosis [ 7 ]), infections [ 8 ], strokes [ 9 ], traumatic injuries [ 10 ], inflammatory pain [ 11 ], postoperative cognitive impairment [ 12 ], epilepsy [ 13 ], and depression [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of baixiangdan capsules on anti-neuroinflammation: combining dry and wet experiments

Liu

Zhao

et al. 2023

Aging

View full text Add to dashboard Cite

Neuroinflammation plays an important role in the pathogenesis of neurological disorders, and despite intensive research, treatment of neuroinflammation remains limited. BaiXiangDan capsule (BXD) is widely used in clinical practice. However, systematic studies on the direct role and mechanisms of BXD in neuroinflammation are still lacking. We systematically evaluated the potential pharmacological mechanisms of BXD on neuroinflammation using network pharmacological analysis combined with experimental validation. Multiple databases are used to mine potential targets for bioactive ingredients, drug targets and neuroinflammation. GO and KEGG pathway analysis was also performed. Interactions between active ingredients and pivotal targets were confirmed by molecular docking. An experimental model of neuroinflammation was used to evaluate possible therapeutic mechanisms for BXD. Network pharmacological analysis revealed that Chrysoeriol, Kaempferol and Luteolin in BXD exerted their anti-neuroinflammatory effects mainly by acting on targets such as NCOA2, PIK3CA and PTGS2. Molecular docking results showed that their average affinity was less than −5 kcal/mol, with an average affinity of −8.286 kcal/mol. Pathways in cancer was found to be a potentially important pathway, with involvement of PI3K/AKT signaling pathways. In addition, in vivo experiments showed that BXD treatment ameliorated neural damage and reduced neuronal cell death. Western blotting, RT-qPCR and ELISA analysis showed that BXD inhibited not only the expression of IL-1β, TNF-α and NO, but also NF-κB, MMP9 and PI3K/AKT signaling pathways. This study applied network pharmacology and in vivo experiments to explore the possible mechanisms of BXD against neuroinflammation, providing insight into the treatment of neuroinflammation.

show abstract

Neuroinflammation in Pathogenesis of Audiogenic Epilepsy: Altered Proinflammatory Cytokine Levels in the Rats of Krushinsky–Molodkina Seizure-Prone Strain

Cited by 5 publications

References 67 publications

Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats

Audiogenic Seizures and Social Deficits: No Aggravation Found in Krushinsky–Molodkina Rats

D1-Like and D2-Like Dopamine Receptors in the Rat Prefrontal Cortex: Impacts of Genetic Generalized Epilepsies and Social Behavioral Deficits

Mechanism of baixiangdan capsules on anti-neuroinflammation: combining dry and wet experiments

Contact Info

Product

Resources

About