Therapeutic effects of Lacosamide in a rat model of traumatic brain injury: A histological, biochemical and electroencephalography monitoring study

Mete, Mesut; Alpay, Şüheda; Aydemir, Işıl; Ünsal, Ülkün Ünlü; Çöllü, Fatih; Özel, Hasan Fehmi; Duransoy, Yusuf Kurtuluş; Kutlu, Necíp; Tuğlu, Mehmet İbrahim

doi:10.1016/j.injury.2021.02.055

Cited by 6 publications

(9 citation statements)

References 29 publications

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“…Solcoseryl (deproteinated calf blood dialysate) administration to brain-injured rats during the post-traumatic period resulted in improved EEG patterns, paralleled by restored vertical and horizontal activity in the Open field test [35]. In another study, an anticonvulsant agent lacosamide normalized the delta strength of EEG simultaneously with a decrease in oxidative stress and apoptosis in traumatized rats [36]. In a rat bilateralcarotid-artery occlusion model of cerebral ischemia, pretreatment with vinpocetine and melatonin positively affected EEG parameters in surviving animals, whose number was increased to 80.0% vs. 34.8% in untreated controls [37].…”

Section: Discussionmentioning

confidence: 99%

Effects of Alpha-2 Adrenergic Agonist Mafedine on Brain Electrical Activity in Rats after Traumatic Brain Injury

et al. 2021

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The search for and development of new neuroprotective (or cerebroprotective) drugs, as well as suitable methods for their preclinical efficacy evaluation, are priorities for current biomedical research. Alpha-2 adrenergic agonists, such as mafedine and dexmedetomidine, are a highly appealing group of drugs capable of reducing neurological deficits which result from brain trauma and vascular events in both experimental animals and human patients. Thus, our aim was to assess the effects of mafedine and dexmedetomidine on the brain’s electrical activity in a controlled cortical-impact model of traumatic brain injury (TBI) in rats. The functional status of the animals was assessed by electrocorticography (ECoG), using ECoG electrodes which were chronically implanted in different cortical regions. The administration of intraperitoneal mafedine sodium at 2.5 mg∙kg−1 at 1 h after TBI induction, and daily for the following 6 days, restored interhemispheric connectivity in remote brain regions and intrahemispheric connections within the unaffected hemisphere at post-TBI day 7. Animals that had received mafedine sodium also demonstrated an improvement in cortical responses to photic and somatosensory stimulation. Dexmedetomidine at 25 μg∙kg−1 did not affect the brain’s electrical activity in brain-injured rats. Our results confirm the previously described neuroprotective effects of mafedine sodium and suggest that ECoG registration and analysis are a viable method evaluating drug efficacy in experimental animal models of TBI.

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Section: Discussionmentioning

confidence: 99%

Effects of Alpha-2 Adrenergic Agonist Mafedine on Brain Electrical Activity in Rats after Traumatic Brain Injury

et al. 2021

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“…Two observers blinded to age groups evaluated the staining scores independently. The immunohistochemical (IHC) assay was performed thrice [ 19 ].…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

“…The results of histopathology and IHC stainings were analyzed by one-way analysis of variance (ANOVA) by Tukey–Kramer multiple comparisons test. The differences were given as mean ± standard deviation (SD) among groups, and the p-value as ≤0.05 was considered statistically significant [ 19 ].…”

Section: Patients Materials and Methodsmentioning

confidence: 99%

Investigation of distribution of GSK-3β signal pathway by age groups in cases of ulcerative colitis

Özbey¹,

Aydemir²

2023

Rom J Morphol Embryol

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Ulcerative colitis (UC), one of the inflammatory bowel diseases, has been reported to increase in recent years. Although the exact cause is unknown, disruptions in the molecular pathways are thought to trigger UC. We aimed to examine the distributions of glycogen synthase kinase-3beta (GSK-3β), nuclear factor-kappa B (NF-κB) and wingless/int-1 (Wnt-1) in different age groups diagnosed with UC. Patients diagnosed with UC were divided into four groups according to their ages: Group 1, aged 18–30 (n=20); Group 2, aged 31–45 (n=20); Group 3, aged 46–60 (n=20); Group 4, aged 61–75 (n=20). Tissue sections were histochemically stained to examine the parameters of epithelial cell height, length of crypt, thickness of muscularis mucosa and extent of submucosal fibrosis. The immunohistochemistry assay was performed using cell survival and for GSK-3β, NF-κB and Wnt-1 cell growth markers. Immunoreactivities were evaluated using H-score and analyzed using the one-way analysis of variance (ANOVA) test for statistics. It was detected a decrease in the histopathological parameters whereas the immunoreactivities of GSK-3β, NF-κB and Wnt-1 were increased with increasing age. The levels of GSK-3β immunoreactivity were similar in both epithelium and submucosa in all groups. NF-κB immunoreactivity was higher in submucosa of Groups 1, 2 and 3, while Wnt-1 was enhanced in Groups 1 and 3. The results of histopathology showed that the integrity of the epithelial tissue in the colon deteriorated with increasing age. The expressions of GSK-3β, NF-κB and Wnt-1 were detected in all age groups. We thought that there was a synergistic activation between these three markers. Nevertheless, studies are needed to investigate this molecular pathway.

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“…showed that LCM has neuroprotective, antiapoptotic, and antioxidative stress effects in their adult rat model study in 2021 (22). Although these results provide evidence that LCM is safe for use in adults, we think that its effects in the embryonic period are different.…”

Section: Discussionmentioning

confidence: 83%

Evaluation of anti-epileptic Lacosamide treatment on neural tube development: Chick embryo experimental model

et al. 2022

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Objective: Even if epileptic women can give birth to healthy babies, the rates of premature birth, low birth weight, fetal and neonatal death risk, congenital malformations and growth retardation in pregnant women who use the antiepileptic drugs (AEDs) are high compared to the population. The present study aimed to examine the effects of AED Lacosamide (LCM) during pregnancy on the fetus in terms of neuronal and embryonic development in 48-hour chick embryo model. Material and Methods: 40SPF fertilized eggs divided into 4 equal numbers. At the 28th hour, LCM was applied in the sub-blastoderm, and the experiment was terminated at the 48th hour. Embryos were evaluated morphologically by neural tube position, somite number, and cranio-caudal length. Histopathologically, hematoxylin-eosin, Caspase-3 immunohistochemistry, and TUNEL staining were performed and and assessed for cell death. Results: LCM adversely affected neural tube position in groups 3 and 4 compared to control. In addition, it regressed embryonic development by decreasing somite number and craniocaudal length in groups 3 and 4. When evaluated in terms of apoptotic cell death, LCM increased caspase-3 immunoreactivity and the number of TUNEL-positive cells in groups 3 and 4, respectively (p=0.002), (p≤0.001). Conclusion: LCM was caused to regression of embryonic development and impaired neural tube position in early chick embryo model, dose-dependent manner. It increased cell death and showed teratogenic effects in the early embryo model. The usage of LCM for pregnant women should be considered carefully. It is obvious that more preclinic studies are needed to demonstrate LCM effects comprehensively.

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Therapeutic effects of Lacosamide in a rat model of traumatic brain injury: A histological, biochemical and electroencephalography monitoring study

Cited by 6 publications

References 29 publications

Effects of Alpha-2 Adrenergic Agonist Mafedine on Brain Electrical Activity in Rats after Traumatic Brain Injury

Effects of Alpha-2 Adrenergic Agonist Mafedine on Brain Electrical Activity in Rats after Traumatic Brain Injury

Investigation of distribution of GSK-3β signal pathway by age groups in cases of ulcerative colitis

Evaluation of anti-epileptic Lacosamide treatment on neural tube development: Chick embryo experimental model

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