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      Protective effect of compound Danshen ( Salvia miltiorrhiza) dripping pills alone and in combination with carbamazepine on kainic acid-induced temporal lobe epilepsy and cognitive impairment in rats

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          Abstract

          Context: Temporal lobe epilepsy (TLE) is resistant to antiepileptic drugs (AEDs) and is associated with cognitive impairment. The modern Chinese medicine, compound Danshen dripping pills (CDDP), is clinically effective in treating epilepsy and improving cognitive impairment.

          Objective: This study evaluated the protective effects of CDDP alone and in combination with carbamazepine (CBZ) on kainic acid-induced TLE and cognitive impairment in rats.

          Materials and methods: Sprague–Dawley rats were randomly divided into five groups: control (sham operated), model, CDDP, CBZ and combined. A TLE model was then created via bilateral intrahippocampal injection of 0.35 μg kainic acid (KA). Rats received CDDP (85 mg/kg), CBZ (100 mg/kg) or combined (85 mg/kg CDDP +100 mg/kg CBZ) via intragastric administration for 90 d, respectively. Seizure intensity, apoptosis and glial cell line-derived neurotrophic factor (GDNF) were measured. Furthermore, the improvement in cognitive impairment and hippocampal neuronal damage was evaluated.

          Results: CDDP combined with CBZ significantly decreased seizure severity and frequency ( p < 0.05) and ameliorated cognitive impairment ( p < 0.05). The model group showed a significant reduction of neurons and Bcl-2/Bax expression in the hippocampus CA3 area ( p < 0.01), the combined groups significantly reversed these change ( p < 0.01). GDNF expression in the combined groups showed a clear increase over the model group ( p < 0.05).

          Conclusion: These findings support the use of CDDP as an adjuvant drug for the treatment of TLE and cognitive deficit. Its mechanism might be related to an anti-apoptosis effect and up-regulation of GDNF.

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          Most cited references44

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          Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial.

          Despite reported success, surgery for pharmacoresistant seizures is often seen as a last resort. Patients are typically referred for surgery after 20 years of seizures, often too late to avoid significant disability and premature death. We sought to determine whether surgery soon after failure of 2 antiepileptic drug (AED) trials is superior to continued medical management in controlling seizures and improving quality of life (QOL). The Early Randomized Surgical Epilepsy Trial (ERSET) is a multicenter, controlled, parallel-group clinical trial performed at 16 US epilepsy surgery centers. The 38 participants (18 men and 20 women; aged ≥12 years) had mesial temporal lobe epilepsy (MTLE) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 brand-name AEDs. Eligibility for anteromesial temporal resection (AMTR) was based on a standardized presurgical evaluation protocol. Participants were randomized to continued AED treatment or AMTR 2003-2007, and observed for 2 years. Planned enrollment was 200, but the trial was halted prematurely due to slow accrual. Receipt of continued AED treatment (n = 23) or a standardized AMTR plus AED treatment (n = 15). In the medical group, 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery. The primary outcome variable was freedom from disabling seizures during year 2 of follow-up. Secondary outcome variables were health-related QOL (measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [QOLIE-89] overall T-score), cognitive function, and social adaptation. Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up (odds ratio = ∞; 95% CI, 11.8 to ∞; P < .001). In an intention-to-treat analysis, the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant (12.6 vs 4.0 points; treatment effect = 8.5; 95% CI, -1.0 to 18.1; P = .08). When data obtained after surgery from participants in the medical group were excluded, the effect of surgery on QOL was significant (12.8 vs 2.8 points; treatment effect = 9.9; 95% CI, 2.2 to 17.7; P = .01). Memory decline (assessed using the Rey Auditory Verbal Learning Test) occurred in 4 participants (36%) after surgery, consistent with rates seen in the literature; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes. Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group. Among patients with newly intractable disabling MTLE, resective surgery plus AED treatment resulted in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone. Given the premature termination of the trial, the results should be interpreted with appropriate caution. clinicaltrials.gov Identifier: NCT00040326.
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            The neurobiology of antiepileptic drugs.

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              Uncovering the neurobehavioural comorbidities of epilepsy over the lifespan.

              Epilepsy is a common neurological disorder that is complicated by psychiatric, cognitive, and social comorbidities that have become a major target of concern and investigation in view of their adverse effect on the course and quality of life. In this report we define the specific psychiatric, cognitive, and social comorbidities of paediatric and adult epilepsy, their epidemiology, and real life effects; examine the relation between epilepsy syndromes and the risk of neurobehavioural comorbidities; address the lifespan effect of epilepsy on brain neurodevelopment and brain ageing and the risk of neurobehavioural comorbidities; consider the overarching effect of broader brain disorders on both epilepsy and neurobehavioural comorbidities; examine directions of causality and the contribution of selected epilepsy-related characteristics; and outline clinic-friendly screening approaches for these problems and recommended pharmacological, behavioural, and educational interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Pharm Biol
                Pharm Biol
                IPHB
                iphb20
                Pharmaceutical Biology
                Taylor & Francis
                1388-0209
                1744-5116
                2018
                21 March 2018
                : 56
                : 1
                : 217-224
                Affiliations
                [a ] Department of Pharmacy, Lanzhou University Second Hospital , Lanzhou, China;
                [b ] Department of Pharmacy, Huaihe Hospital of Henan University , Kaifeng, China;
                [c ] College of Pharmacy, Lanzhou University , Lanzhou, China
                Author notes

                *These authors are co-first authors, and have made an equal contribution to this work.

                Supplemental data for this article can be accessed here .

                CONTACT Haisheng Jiao haisjiao@ 123456163.com Department of Pharmacy, Lanzhou University Second Hospital , Lanzhou730030, China
                Article
                1432665
                10.1080/13880209.2018.1432665
                6130614
                29560767
                a4cc18d2-8c61-4f94-a297-1ee14d335c0b
                © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 August 2017
                : 30 December 2017
                : 15 January 2018
                Page count
                Pages: 8, Words: 5827
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81550048
                This study was supported by the National Natural Science Foundation of China [Grant no. 81550048].
                Categories
                Research Article

                intractable epilepsy,antiepileptic drugs,traditional chinese medicine,hippocampal ca3 area,glial cell line-derived neurotrophic factor,anti-apoptosis

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