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.
Subject(s)
Anticonvulsants/pharmacology , Behavior, Animal/drug effects , CA3 Region, Hippocampal/drug effects , Carbamazepine/pharmacology , Cognition/drug effects , Cognitive Dysfunction/prevention & control , Drugs, Chinese Herbal/pharmacology , Epilepsy, Temporal Lobe/prevention & control , Kainic Acid , Animals , Apoptosis/drug effects , CA3 Region, Hippocampal/metabolism , CA3 Region, Hippocampal/pathology , CA3 Region, Hippocampal/physiopathology , Camphanes , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/psychology , Disease Models, Animal , Drug Therapy, Combination , Epilepsy, Temporal Lobe/metabolism , Epilepsy, Temporal Lobe/pathology , Epilepsy, Temporal Lobe/physiopathology , Escape Reaction/drug effects , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Male , Maze Learning/drug effects , Panax notoginseng , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats, Sprague-Dawley , Reaction Time/drug effects , Salvia miltiorrhiza , Time Factors , bcl-2-Associated X Protein/metabolismABSTRACT
Objective To observe the effect of electroacupuncture(EA) on Calbindin D28K(CB) expression and apoptosis in hippocampus in hyperlipemia rats with concomitant cerebral ischemia(CI).Methods Forty male SD rats were rando-mized into control,hyperlipemia+CI(model),acupuncture Ⅰ,and acupuncture Ⅱ groups,with 10 cases in each.Hyperlipemia model was established by feeding the animals with high fat forage for 6 weeks and CI model established by occlusion of the unila-teral middle cerebral artery.For rats of acupuncture Ⅰ group,EA(1-3 mA,15 Hz) was applied to bilateral "Sanyinjiao"(SP 6) and "Fenglong"(ST 40) for 20 min every time,once daily for 10 days before CI.For rats of both acupuncture Ⅰ and Ⅱ groups,after CI,EA was applied to SP 6,ST 40,"Baihui"(GV 20) and "Shuigou"(GV 26) were punctured with filiform needles and stimulated by twirled the needle with hand continuously for 1 min,once daily for 7 days.The apoptotic cells of hippocampal CA 3 area were displayed by TUNEL(terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling) method.CB antibody staining with immunohistochemistry was used to show CB-positive cells which were observed by optic microscope.Results In comparison with control group,the percentage of apoptotic cells of the hippocampal CA 3 area in model group increased considerably(P
