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

Chen Jia,Shanshan Han,Liming Wei,Xiangji Dang,Qianqian Niu,Mengyu Chen,Boqun Cao,Yuting Liu,Haisheng Jiao

doi:10.1080/13880209.2018.1432665

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.

Highlights

Epilepsy is a terrible chronic neurologic disease of brain dysfunction that is characterized by an enduring state of spontaneous recurrent seizures (SRS); it affects approximately 1–2% of the world’s population (Bell and Sander 2001)
Most types of epilepsy can be effectively controlled by the current antiepileptic drugs (AEDs) such as carbamazepine (CBZ), phenytoin and lamotrigine, 20–30% of patients still suffer from poorly controlled epilepsy and develop intractable epilepsy (IE) (Kwan and Brodie 2002; Riazi et al 2010; Engel et al 2012)
Seizures induced by intrahippocampal kainic acid (KA) injection were divided into three stages according to behavioural characteristics: acute phase, incubation period and chronic phase

Summary

Introduction

Epilepsy is a terrible chronic neurologic disease of brain dysfunction that is characterized by an enduring state of spontaneous recurrent seizures (SRS); it affects approximately 1–2% of the world’s population (Bell and Sander 2001). Most types of epilepsy can be effectively controlled by the current antiepileptic drugs (AEDs) such as carbamazepine (CBZ), phenytoin and lamotrigine, 20–30% of patients still suffer from poorly controlled epilepsy and develop intractable epilepsy (IE) (Kwan and Brodie 2002; Riazi et al 2010; Engel et al 2012). In these cases, AEDs are unable to influence the long-term harmful effects of status epilepticus or prevent epileptogenesis (Rogawski and Loscher 2004). Because the neuropathy occurs in the memory-relevant brain region, cognitive impairment is a common and severe comorbidity in patients with TLE (Graham and Gaffan 2005; Holmes 2006; Lin et al 2012).

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