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Objective:To investigate the effects of nimodipine on cognitive function in patients with Alzheimer's disease.Methods:A total of 200 patients with Alzheimer's disease who received treatment in Shuangqiao Hospital from January 2019 to January 2022 were included in this study. They were randomly divided into a control group and an observation group ( n = 100/group). The control group was treated with Donepezil. The observation group was treated with nimodipine and Donepezil. Before and 2 months after treatment, mental status and cognitive function were evaluated in each group. Results:After treatment, total response rate in the observation group was significantly higher than that in the control group [95% (95/100) vs. 81% (81/100), χ2 = 9.58, P < 0.05]. Alzheimer's disease assessment scale cognitive subscale score was significantly lower after treatment compared with before treatment in each group ( P < 0.05). Mini-mental State Examination score was significantly higher after treatment compared with before treatment in each group ( P < 0.05). Alzheimer's disease assessment scale cognitive subscale score in the observation group was significantly lower than that in the control group [(17.38 ± 1.95) points vs. (29.63 ± 3.39) points, t = -3.26, P < 0.05]. Mini-mental State Examination score in the observation group was significantly higher than that in the control group [(23.47 ± 4.59) points vs. (18.68 ± 3.91) points, t = 2.14, P < 0.05]. Conclusion:Nimodipine can improve cognitive function in patients with Alzheimer's disease.
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Objective:To investigate the efficacy of Compound Musk combined with nimodipine combined with minimally invasive surgery in the treatment of hypertensive cerebral hemorrhage and the effects on serum inflammation, stress and apoptosis.Methods:Prospective research methods was used. A total of 118 patients with hypertensive intracerebral hemorrhage who received treatment in the First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine from March 2017 to January 2021 were randomly divided into control group and Compound Musk group (59 cases in each group). After minimally invasive surgery, patients in the control group were treated with nimodipine on the basis of conventional treatment, while patients in the Compound Musk group were treated with compound musk on the basis of the control group. After 2 weeks, the efficacy was evaluated and the levels of serum inflammatory indexes, oxidative stress indexes and apoptosis indexes were measured.Results:The total effective rate in Compound Musk group was higher than that in control group: 98.3% (58/59) vs. 88.1% (52/59), and the difference was statistically significant ( P<0.05). After 2 weeks of treatment, serum inflammatory indexes including nuclear factor-κB (NF-κB), interleukin-1β (IL-1β), matrix metalloproteinase-3 (MMP-3), matrix metalloproteinase-9 (MMP-9); apoptosis indexes including soluble Fas receptor (sFas), soluble Fas ligand (sFAS-L); oxidative stress indexes including advanced oxidation protein products (AOPP), malondialdehyde (MDA) decreased, and some oxidative stress indexes including glutathione peroxidase (GSH-Px), catalase (CAT) increased. The levels of the above inflammatory indexes, apoptosis indexes and oxidative stress indexes in Compound Musk group were lower than those in control group, NF-κB: (18.96 ± 2.17) ng/L vs. (24.10 ± 3.23) ng/L, IL-1β: (12.88 ± 1.74) ng/L vs. (15.19 ± 1.63) ng/L, MMP-3: (5.62 ± 0.95) ng/L vs. (7.97 ± 0.86) ng/L, MMP-9: (7.07 ± 0.86) ng/L vs. (9.26 ± 1.13) ng/L, sFas: (3.24 ± 0.38) μg/L vs. (4.19 ± 0.53) μg/L, sFas-L: (209.17 ± 24.39) ng/L vs. (288.54 ± 37.61) ng/L, AOPP: (10.76 ± 1.84) μg/L vs. (13.51 ± 2.09) μg/L, MDA: (2.87 ± 0.32) μmol/L vs. (3.45 ± 0.34) μmol/L, and the differences were statistically significant ( P<0.05). Some of the above oxidative stress indexes were higher than those in control group, GSH-Px: (3 274.91 ± 376.09) U/L vs. (2 854.19 ± 325.22) U/L, CAT: (60.82 ± 7.43) U/L vs. (52.17 ± 6.48) U/L, the differences were statistically significant ( P<0.05). During treatment, there was no significant difference in the incidence of rash, diarrhea, drug-induced liver and myocardial injury between two groups ( P>0.05). Conclusions:Compound Musk has a positive effect on improving the curative effect and internal environment of patients with hypertensive intracerebral hemorrhage after minimally invasive surgery, and will not increase the occurrence of serious adverse reactions.
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Abstract Background Subarachnoid hemorrhage (SAH) is an uncommon and serious subtype of stroke, which leads to the loss of the patient's ability to produce and live for many years. Objective To investigate the clinical effect of nimodipine in the treatment of SAH. Methods Electronic databases including China National Knowledge Infrastructure (CNKI), VIP, SinoMed, China Master's Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed and Embase were searched from 2010 and 2021. All randomized controlled trials evaluating the efficacy of nimodipine in the treatment of SAH were included in our meta-analysis. The patients were divided into control group and treatment group. Meta-analysis was performed with Stata16.0 software. Results A total of 10 studies were included. Compared with the control group, the treatment group had higher effective rate (OR = 3.21, 95% CI: 2.25, 4.58; p < 0.001), and lower incidence of adverse reactions (OR = 0.35, 95% CI: 0.19, 0.67; p = 0.001). Before treatment, no significant differences were identified in middle cerebral artery blood flow velocity and Glasgow coma scale (GCS) score between the two groups. However, after treatment, the middle cerebral artery blood flow velocity (SMD = — 1.36, 95% CI: —2.28, —0.49; p = 0.002) and GCS score (SMD = 1.24, 95% CI: 0.58, 1.89; p < 0.001) in the treatment group were significantly better than those in the control group. Conclusions Nimodipine is effective in the treatment of SAH, lowering incidence of adverse reactions and therefore improving the prognosis of patients.
Resumo Antecedentes Hemorragia subaracnóidea (SAH) é um subtipo raro e grave de acidente vascular cerebral (AVC), o que leva à perda da capacidade do paciente de produzir e viver por muitos anos. Objetivo Investigar o efeito clínico da nimodipina no tratamento da SAH. Métodos As bases de dados eletrônicas, incluindo a China National Knowledge Infrastructure (CNKI), VIP, SinoMed, Masters Theses Full-text Database (CMFD), China Doctoral Dissertations Full-text Database (CDFD), Cochrane Library, PubMed e Embase foram pesquisadas no período de 2010 a 2021. Todos os ensaios controlados aleatorizados que avaliam a eficácia da nimodipina no tratamento da SAH foram incluídos na nossa meta-análise. Os pacientes foram divididos em grupo controle e grupo de tratamento. Meta-análise foi realizada com o software Stata 16.0. Resultados Foram incluídos um total de dez estudos. Em comparação com o grupo controle, o grupo de tratamento tinha uma taxa mais elevada (OR = 3,21, 95% CI: 2,25, 4,58; p < 0,001), e menor incidência de reações adversas (OR = 0,35, 95% CI: 0,19, 0,67; p = 0,001). Antes do tratamento, não foram identificadas diferenças significativas na velocidade média do fluxo sanguíneo da artéria cerebral e na pontuação de Glasgow coma scale (GCS) entre os dois grupos. No entanto, após o tratamento, a velocidade média do fluxo sanguíneo da artéria cerebral (SMD = −1,36, 95% CI: −2,28, 0,49; p = 0,002) e a pontuação do GCS (SMD = 1,24, 95% CI: 0,58, 1,89; p < 0,001) no grupo de tratamento foram significativamente melhores do que os do grupo controle. Conclusões A nimodipina é eficaz no tratamento da SAH, diminuindo a incidência de reações adversas e, consequentemente, melhorando o prognóstico dos doentes.
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Objective:To evaluate the effect of nimodipine on postoperative cognitive function in elderly patients undergoing carotid endarterectomy.Methods:Eighty-two American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes, aged 65-80 yr, scheduled for elective carotid endarterectomy under general anesthesia, were divided into 2 groups ( n=41 each) using a random number table method: control group (group C) and nimodipine group (group N). Nimodipine 7.5 μg·kg -1·h -1 was intravenously infused starting from the beginning of surgery until the end of surgery in group N, while the equal volume of normal saline was given in group C. Before infusing nimodipine (T 1), before placing the the shunt (T 2), at 10 min after placing the the shunt (T 3) and at 10 min after releasing carotid artery (T 4), blood samples were taken from the radial artery and jugular bulb for blood gas analysis.Jugular venous blood oxygen content, arterio-jugular difference of oxygen content, and cerebral oxygen extraction ratio were calculated.The concentrations of S100β protein in serum of the jugular bulb were measured by enzyme-linked immunosorbent assay.Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) Scale (Chinese version) at 1 day before surgery and 1, 3 and 7 days after surgery, and the occurrence of cognitive dysfunction (MoCA score<26) was recorded within 7 days after operation. Results:Compared with group C, MoCA scores were significantly increased at each time point after surgery, and the incidence of cognitive dysfunction was decreased (27% vs.17%), and the jugular venous blood oxygen content was increased, and arterio-jugular difference of oxygen content, cerebral oxygen extraction ratio, and concentrations of serum S100β protein were decreased at T 2-4 in group N ( P<0.05). Conclusions:Nimodipine can improve the cognitive function after carotid endarterectomy, which may be related to the improvement in intraoperative cerebral oxygen metabolism and reduction of brain injury in elderly patients.
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Objective:To analyze the effect of modified Banxia Baizhu Tianma Decoction combined with Nimodipine on cognitive dysfunction and changes on cerebral blood flows of the patients with chronic cerebral insufficiency (CCCI).Methods:A total of 91 patients with CCCI who received treatment in our hospital from March 2019 to March 2020 were selected and divided into the treatment group ( n=46) and the control group ( n=45), according to random number table method. The control group was treated with Nimodipine oral treatment, and the treatment group was treated with modified Banxia Baizhu Tianma Decoction on the basis of the control group treatment. Both groups were treated for 2 weeks. The Traditional Chinese Medicine (TCM) syndrome scores were performed before and after treatment, and transcranial Doppler ultrasound was used to detect the average blood flow of bilateral vertebral arteries (VA), basilar arteries (BA), internal carotid arteries (ICA) and middle cerebral arteries (MCA). The whole blood viscosity high shear (HS), whole blood low shear (LS), plasma viscosity (PV), fibrinogen (FIB) and hematocrit (HCT) were detected by automatic blood rheometerusing. The Montreal Cognitive Assessment Scale (MoCA) was used to assess the degree of cognitive impairment and evaluate the clinical efficacy. Results:The total effective rate was 91.3% (42/46) in the treatment group and 73.3% (33/45) in the control group, with a statistically significant difference between the two groups ( χ2=5.07, P=0.024). The scores of dizziness, headache, forgetfulness, insomnia and total scores in the treatment group were significantly lower than those in the control group after treatment ( t values were 8.59, 7.79, 3.92, 4.11, 5.01, all Ps<0.01), and the MoCA score (25.13±2.16 vs. 23.88±2.70; t=2.44, P=0.017) in the treatment group significantly higher than that in the control group. After treatment, VA [(35.49±4.08) cm/s vs. (32.17±4.25) cm/s, t=3.80], BA [(36.99±3.79) cm/s vs. (33.76±4.12) cm/s, t=3.89], ICA [(62.49±5.07) cm/s vs. (58.91±5.31) cm/s, t=3.29], MCA [(70.09±5.04) cm/s vs. (67.12±5.85) cm/s, t=2.60] in the treatment group was significantly higher than those in the control group ( P<0.01). After treatment, the levels of HS, LS, PV, Fg, and HCT in the treatment group were significantly lower than those in the control group ( t values were 2.37, 4.35, 2.23, 2.42, 2.20, P<0.05 or P<0.01). Conclusion:Modified Banxia Baizhu Tianma Decoction combined with Nimodipine tablets can relieve the clinical symptoms of CCCI patients, improve blood flow velocity, blood rheology level and cognitive function, and improve clinical efficacy.
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Ischemic stroke presents a leading cause of mortality and morbidity worldwide. Theaflavic acid (TFA) is a theaflavin isolated from black tea that exerts a potentially neuro-protective effect. However, the dynamic properties of TFA-mediated protection remain largely unknown. In the current study, we evaluated the function of TFA in the mitochondria apoptotic pathway using mathematical modeling. We found that TFA-enhanced B-cell lymphoma 2 (Bcl-2) overexpression can theoretically give rise to bistability. The bistability is highly robust against parametric stochasticity while also conferring considerable variability in survival threshold. Stochastic simulations faithfully match the TFA dose response pattern seen in experimental studies. In addition, we identified a dose- and time-dependent synergy between TFA and nimodipine, a clinically used neuro-protective drug. This synergistic effect was enhanced by bistability independent of temporal factors. Precise application of pulsed doses of TFA can also promote survival compared with sustained TFA treatment. These data collectively demonstrate that TFA treatment can give rise to bistability and that synergy between TFA and nimodipine may offer a promising strategy for developing therapeutic neuro-protection against ischemic stroke.
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Objective:To investigate Shenqi Fuzheng Injection combined with nimodipine in the treatment of convalescent-phase cerebral infarction and its effects on neurocognitive function, hemorheology and T cell subsets. Methods:A total of 108 patients with cerebral infarction in the convalescent phase who received treatment in Hangzhou Hospital of Traditional Chinese Medicine, China between April 2016 and December 2019 were included in this study. They were randomly assigned to receive either nimodipine treatment (control group, n = 54) or treatment with Shenqi Fuzheng Injection combined with nimodipine (study group, n = 54). Curative effects and changes in neurocognitive function, hemorheology and T cell subsets after treatment relative to before treatment were compared between the control and study groups. Results:Total effective rate in the study group was significantly higher than that in the control group [90.74% (49/54) vs. 75.93% (41/54), χ2 = 4.267, P = 0.039]. After 2 weeks of treatment, whole blood viscosity at a high shear rate, whole blood viscosity at a low shear rate, plasma viscosity in the study group were (4.17 ± 0.24) mPa/s, (9.27 ± 1.98) mPa/s, (1.07 ± 0.19) mPa/s, respectively, which were significantly lower than those in the control group [(4.52 ± 0.31) mPa/s, (13.69 ± 2.13) mPa/s, (1.34 ± 0.23) mPa/s, t = 6.560, 11.169, 6.651, all P < 0.05]. The proportion of CD 3+ cells, CD 4+ and CD 4+/CD 8+ in the study group was (48.59 ± 4.59) %, (44.24 ± 6.17) % and (1.91 ± 0.17) respectively, which were significantly higher than those in the control group [(44.97 ± 5.31) %, (39.55 ± 5.13) %, (1.47 ± 0.22), t = 3.790, 4.295, 11.629, all P < 0.05]. The proportion of CD 8+ cells in the study group was significantly lower than that in the control group [(23.13 ± 5.62) % vs. (26.97 ± 4.26) %, t = 4.001, P < 0.05]. Mini-Mental State Examination score in the study group was significantly higher than that in the control group [(28.87 ± 0.85) points vs. (27.91 ± 1.45) points, t = 4.197, P < 0.05]. National Institute Health of Stroke Scale score in the study group was significantly lower than that in the control group [(9.63 ± 2.19) points vs. (15.27 ± 1.97) points, t = 14.070, P < 0.05]. Conclusion:Shenqi Fuzheng Injection combined with nimodipine can remarkably improve the neurocognitive function, hemorheology and T cell subsets in patients with cerebral infarction in the convalescent phase. The combined method is safe and reliable, and its curative effect is stable.
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Objective: To investigate the expressions of Galectin-3 and matrix metalloproteinase-9 (MMP-9) in brain tissue of the mice with acute cerebral infarction and the intervention effect of nimodipine. and to elucidate the effects of Galectin-3 and MMP-9 in the occurrence and treatment of cerebral infarctioa Methods: A total of 210 mice were randomly divided into control group, model group and nimodipine group (;i~70). In model group and nimodipine group, the acute cerebral infarction models of mice were established by the suture method. The mice in nimodipine group were intraperitoneal
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Objective To investigate the effects of the combination of aspirin and nimodipine preconditioning on the prognosis of cerebral ischemia-reperfusion. Methods Eighty healthy male SD rats were randomly divided into sham group, model group, aspirin preconditioning group and aspirin + nimodipine preconditioning group, with 20 rats in each group. The model of cerebral ischemia reperfusion was established. The rats in each group were given intragastric administration for 5 days before the model was established, and the drug was administered daily for 5 days. Sham group and model group were given normal saline; Aspirin preconditioning group was given 50 mg/kg aspirin; Aspirin + nimodipine preconditioning group was given 50 mg/kg aspirin and 10 mg/kg nimodipine. After 2 hours ischemia and 24 hours reperfusion, the animals were neurologically assessed, and then the volume of cerebral infarction was measured by TTC staining. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), thromboxane B2, 6-keto-prostaglandin-la in brain tissue were determined by ELISA. The mRNA expression of Notch 1, Jagged 1 and Hesl in the brain tissues were detected by Real-time PCR, and the expressions of Jaggedl and Hesl, a downstream substance in Notch signaling pathway, were detected by Western blotting. Results The neurological deficit score of the aspirin+nimodipine pretreatment group was significantly lower than model group (P<0. 05) , and the cerebral infarction volume was significantly smaller than other groups. The SOD and 6-keto-prostaglandin 1 in the aspirin pretreatment group and the aspirin plus nimodipine pretreatment group were significantly higher than those in the model group, and the expressions of MDA, thromboxane B2 and thromboxane B2/6-keto-prostaglandin 1 were low. In the model group, the changes in the aspirin + nimodipine pretreatment group were more significant (P<0. 05). The expression levels of Notch 1 , Jagged 1 and Hesl mRNA and protein in the aspirin pretreatment group and aspirin + nimodipine pretreatment group were significantly lower than those in the model group (P<0. 05) , and the expression level of aspirin + nimodipine pretreatment group was lower than that of aspirin pretreatment group (P<0. 05). Conclusion The protective effect of aspirin plus nimodipine is superior to aspirin alone, which can significantly improve cerebral ischemia-reperfusion injury in rats, which may be exerted through influencing notch signaling pathway to achieve brain tissue protection.
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The present work aims to enhance the water solubility of nimodipine, a hydrophobic drug, using a solid dispersion(SD) technique. Soluplus® as a novel hydrophilic polymeric carrier was used. Nimodipine-Soluplus® SDs (1:10) wereprepared by impregnation technique using supercritical fluid technology (SCF) and compared with the ones whichwere prepared by conventional hot-melt (HM) method. The solubility and the in vitro release study of the raw drug,solid dispersions, and the corresponding physical mixtures were characterized and compared. The prepared SD bySCF technology showed 77-fold increase in nimodipine solubility, in comparison to 48-fold increase when preparedby HM and 7.7-fold when physically mixed. Moreover, they showed the highest percentage of nimodipine cumulativerelease within the studied period. The results were confirmed the amorphous transfer of the drug into the polymermatrix which was assured by the powder X-ray diffraction and the thermal analysis. In addition to the hydrogen bondformation between nimodipine and Soluplus®, which was evident in the FTIR spectra; A weakening of peak related tonimodipine N–H stretching and C=O of the ester group. Nimodipine solid dispersion with Soluplus® using the SCFtechnology might represent a promising formulation for nimodipine to enhance its oral bioavailability
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We report a 39-year-old male with an aneurysmal subarachnoid hemorrhage without hydrocephalus, in whom a right choroidal aneurysm was early excluded by endovascular coil insertion. Intracranial pressure (PIC) and cerebral oxygenation (PtiO2) sensors for neuromonitoring were installed due to a persistent comatose state. From the 3rd day, neuromonitoring became altered. CT angiography and cerebral angiography showed severe proximal and distal vasospasm (VE) of the middle (ACM) and anterior (ACA) right cerebral arteries. VE was treated with angioplasty and intravenous nimodipine. Forty eight hours later, despite hemodynamic maximization, neuromonitoring became altered again, mainly explained by a decrease in PtiO2 below 15 mmHg. A severe VE in ACM and right ACA was confirmed by angiography. Given the presence of an early and recurrent VE, which was associated with a decrease in cerebral oxygenation, internal carotid micro-catheters for continuous nimodipine infusion were installed. This therapy maintained a normal neuromonitoring for 15 days. During this period, attempts were done to decrease or discontinue the infusion, but the patient presented parallel falls of cerebral oxygenation or decreased cerebral perfusion observed with perfusion CT, interpreted as persistent VE. Finally, the infusion was stopped at day 15 without significant complication. We conclude that intra-arterial nimodipine continuous infusion in refractory VE can be useful and safe in selected patients. Multimodal neuromonitoring is essential.
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Humans , Male , Adult , Subarachnoid Hemorrhage/complications , Nimodipine/therapeutic use , Cerebral Angiography , Coma , Computed Tomography AngiographyABSTRACT
Objective@#To evaluate the clinical efficacy and safety of nimodipine combine with butylphthalide in the treatment of patients with mild to moderate vascular cognitive impairment(VCI).@*Methods@#From January 2012 to December 2016, 100 patients with mild to moderate VCI in Jinhua Municipal Central Hospital were randomly divided into control group(n=50) and treatment group(n=50) according to the random number table method.The control group received butylphthalide capsule, 200 mg po tid.The treatment group received nimodipine tablets, 40mg po tid, on the basis of the control group.The two groups of patients were treated for 24 weeks.Montreal cognitive assessment(MoCA), activities of daily living(ADL), serum hs-CRP, IL-6, TNF-α, clinical efficacy and adverse drug reactions were compared after treatment.@*Results@#After treatment, the scores of MoCA and ADL in the treatment group were (24.32±2.87)points, (59.22±6.17)points, respectively, which were significantly higher than those in the control group[(22.76±2.67)points, (55.63±6.3)points, t=2.814, 2.870, all P<0.05]. The effective rates in the treatment group and control group were 74.00%(37/50), 52.00%(26/50), respectively, and there was statistically significant difference between the two groups(χ2=5.191, P<0.05). After treatment, the levels of hs-CRP[(189.51±23.27)mg/L vs.(211.51±25.51)mg/L], IL-6[(76.42±9.86)ng/L vs.(95.85±10.23)ng/L], TNF-α[(0.24±0.08)ng/L vs.(0.32±0.10)ng/L] between the treatment group and the control group had statistically significant differences(t=4.505, 9.670, 4.417, all P<0.05). The adverse drug reactions were nausea and vomiting in 3 cases in the control group(6.00%), nausea and vomiting in 3 cases and hypotension in 1 case in the treatment group(8.00%), and there was no statistically significant difference between the two groups(P>0.05).@*Conclusion@#Nimodipine combined with butylphthalide in the treatment of mild to moderate VCI is effective and has high safety.
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Objective: To explore the effect of ginsenoside Rgl on the ubiquitin-modified protein aggregation in the cortex after cerebral ischemia reperfusion (I / R) injury in the rats, and to further clarify the therapeutic mechanism of ginsenoside Rgl in the cerebral I/R injury. Methods: The middle cerebral artery occlusion (MCAO) model was set up with suture method for 1. 5 h of embolization. A total of 72 rats were divided into sham operation group, I/R model group, positive drug control (nimodipine) group, low, middle, and high doses 10, 20, and 40 mg ' k g - 1) of ginsenoside Rgl groups. All 12 rats in each group were given intraperitoneal injection. TTC staining and Longa' s score method were used to detect the infarction areas and the neurological deficit scores of the rats in various groups 24 h after modeling. The death of neurons in the cortex and hippocampus after cerebral ischemia of the rats in various groups were observed with HE staining. Immunohistochemistry and Western blotting method were used to detect the expression of ubiquitin-modified protein aggregation in the cortex of the rats in various groups. Results: Compared with I/R group, the percentages of infarction areas of the rats in nimodipine group and ginsenoside Rgl groups were significantly decreased (P < 0 . 05). and the neurological deficit scores were decreased (P < 0 . 05). The HE staining results showed that compared with sham operation group, the neurons in I/R model group were sparse, showing fragmentation and dissolution; compared with I/R model group, the phenomena of cell nucleus fragmentation, dissolution and powder staining in nimodipine group and different doses of ginsenoside Rgl groups were all improved to different degrees. The immunohistochemical results showed that compared with sham operation group, the positive expression level of ubiquitin-modified protein in I/R model group was increased significantly (P < 0 . 05); compared with I/R model group, the positive expression levels of ubiquitin-modified protein in nimodipine group and different doses of ginsenoside Rgl groups were decreased (P < 0 . 05), especially in high dose of ginsenoside Rgl group (P < 0 . 05). The Western blotting results showed that compared with sham operation group, the level of ubiquitin-modified protein aggregates in I/R model group was significantly increased (P < 0 . 0 5); compared with I/R model group, the levels of ubiquitin-modified protein aggregates in nimodipine group and different doses of ginsenoside Rgl were decreased (P < 0 . 05), especially in high dose of ginsenoside Rgl group. Conclusion: Ginsenoside Rgl can inhibit the formation of ubiquitin-modified protein aggregates induced by I/R injury in the cortex, thereby alleviating the I/R injury in the rats.
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Objective To investigate the effect of nimodipine on autophagy in hippocampal CA1 area of rats with subarachnoid hemorrhage (SAH). Methods Forty-eight male Sprague-Dawley rats were randomly divided into sham operation group (sham group) ,SAH group,SAH + nimodipine group (NMDP group),and SAH + nimodipine + 3-methyladenine group (3-MA group, n = 12 in each group). A SAH animal model was induced by internal carotid artery puncture method. Nimodipine was intraperitoneal
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Objective@#To investigate the effect of nimodipine combined with cerebrospinal fluid replacement on hemoglobin concentration, Toll-like receptor 4 (TLR4) expression level and cerebral vasospasm (CVS) in patients with CVS after aneurysmal subarachnoid hemorrhage (aSAH).@*Methods@#One hundred and twenty patients with CVS after aSAH admitted to the Department of Neurosurgery, the Sixth Medical Center of PLA General Hospital from May 2013 to May 2015 were selected. They were randomly divided into control group and observation group (n=60 in each group). The control group received conventional treatment and nimodipine infusion after embolization of the aneurysms, and the observation group underwent cerebrospinal fluid replacement by lumbar puncture on this basis. The clinical efficacy, Glasgow Coma Scale (GCS) scores, hemoglobin concentration and TLR4 expression levels before and after treatment, and adverse reactions were compared between the two groups.@*Results@#One month after treatment, the improvement rate of vasospasm in the observation group was significantly higher than that in the control group (86.7% vs. 60.0%; χ2=9.590, P=0.002). Three months after the treatment, the good rate of clinical outcome (the modified Rankin Scale score 0-2) was significantly higher than that of the control group (88.3% vs. 58.3%; χ2 =13.807, P<0.001). Before treatment, there were no significant differences in hemoglobin concentration and TLR4 expression levels between the two groups; after treatment, the hemoglobin concentration and TLR4 expression levels of both groups were significantly reduced (P<0.05). Compared with the control group, the hemoglobin concentration (119.9±19.8 g/L vs. 137.6±17.8 g/L; t=3.270, P=0.001) and TLR4 expression level (2.5±1.2 vs. 4.5±1.5; t=8.060, P<0.001) in the observation group decreased more significantly. Multivariate logistic regression analysis showed that hypertension (odds ratio [OR] 5.19, 95% confidence interval [CI] 2.31-6.71), hyperlipidemia (OR 2.70, 95% CI 1.93-4.86), previous history of stroke or transient ischemic attack (OR 6.29, 95% CI 3.23-7.32), smoking (OR 4.80, 95% CI 2.18-6.19), and the TLR4 expression level before treatment (OR 3.28, 95% CI 2.87-6.93) were independently correlated with the lack of improvement in CVS, and cerebrospinal fluid replacement was independently correlated with CVS improvement (OR 0.40, 95% CI 0.14-0.89). There was no significant difference in the incidence of adverse reactions such as blood pressure drop, obstructive hydrocephalus and gastrointestinal hemorrhage between the observation group and the control group, but the incidence of delayed CVS (13.3% vs. 36.7%; χ2=7.510, P=0.006) and secondary cerebral infarction (8.3% vs. 31.7%; χ2=8.800, P=0.003) in the observation group were significantly lower than those of the observation group.@*Conclusion@#Nimodipine infusion combined with cerebrospinal fluid replacement by lumbar puncture affected the hemoglobin concentration and TLR4 expression levels, improved the CVS improvement rate, and significantly improved the clinical outcome in patients with CVS after aSAH.
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Objective :To study influence of nimodipine on neurological function and serum levels of aquaporin (AQP) 4 and macrophage migration‐inhibitory factor (MIF) in aged patients with hypertensive intracerebral hemorrhage (HICH).Methods :A total of 120 aged HICH patients treated in our hospital from Jan 2014 to Jan 2017 were ran‐domly and equally divided into routine treatment group (received puncture removal of hematoma + routine treat‐ment) and nimodipine group (received nimodipine based on routine treatment group ) ,both groups were treated for three weeks.United States National Institutes of Health Stroke Score (NIHSS) score ,brain edema volume ,serum levels of AQP4 ,MIF ,hsCRP and tumor necrosis factor (TNF)‐α ,therapeutic effect and incidence of adverse reac‐tion were measured and compared between two groups before and after treatment .Results :Total effective rate of nimodipine group was significantly higher than that of routine treatment group (88.33% vs .70.00%) , P＝0.013. Compared with routine treatment group after treatment ,there were significant reductions in NIHSS score [ (17.39 ± 3. 08) scores vs .(12. 26 ± 3.74) scores] ,brain edema volume [ (11. 84 ± 2.31) ml vs .(6.68 ± 1.93) ml] ,serum levels of AQP4 [ (2. 79 ± 0. 64) ng／ml vs .(1. 84 ± 0. 52) ng／ml] ,MIF [ (55.39 ± 7. 65) ng／L vs.(43.25 ± 5. 81) ng／L] ,hsCRP [ (18.83 ± 5. 17) mg／L vs.(12. 53 ± 3.87) mg／L] and TNF‐α [ (8. 42 ± 1.37) ng／L vs.(5. 78 ± 1.96) ng／L ] in nimodipine group , P＝0.001 all.There were no severe adverse reactions and no significant differ‐ence in incidence rate of adverse reactions between two groups , P＝0.436. Conclusion :Nimodipine can significantly improve therapeutic effect ,neurological function ,reduce serum AQP4 and MIF levels ,relieve brain edema and in‐flammation in aged HICH patients .
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Objective To investigate the effect of nimodipine combined with cerebrospinal fluid replacement on hemoglobin concentration,Toll-like receptor 4 (TLR4) expression level and cerebral vasospasm (CVS) in patients with CVS after aneurysmal subarachnoid hemorrhage (aSAH).Methods One hundred and twenty patients with CVS after aSAH admitted to the Department of Neurosurgery,the Sixth Medical Center of PLA General Hospital from May 2013 to May 2015 were selected.They were randomly divided into control group and observation group (n =60 in each group).The control group received conventional treatment and nimodipine infusion after embolization of the aneurysms,and the observation group underwent cerebrospinal fluid replacement by lumbar puncture on this basis.The clinical efficacy,Glasgow Coma Scale (GCS) scores,hemoglobin concentration and TLR4 expression levels before and after treatment,and adverse reactions were compared between the two groups.Results One month after treatment,the improvement rate of vasospasm in the observation group was significantly higher than that in the control group (86.7％ vs.60.0％;x2 =9.590,P =0.002).Three months after the treatment,the good rate of clirnical outcome (the modified Rankin Scale score 0-2) was significantly higher than that of the control group (88.3％ vs.58.3％;x2 =13.807,P＜0.001).Before treatment,there were no significant differences in hemoglobin concentration and TLR4 expression levels between the two groups;after treatment,the hemoglobin concentration and TLR4 expression levels of both groups were significantly reduced (P ＜0.05).Compared with the control group,the hemoglobin concentration (119.9 ± 19.8 g/L vs.137.6 ± 17.8 g/L;t =3.270,P =0.001) and TLR4 expression level (2.5 ± 1.2 vs.4.5 ± 1.5;t =8.060,P ＜0.001) in the observation group decreased more significantly.Multivariate logistic regression analysis showed that hypertension (odds ratio [OR] 5.19,95％ confidence interval [CI] 2.31-6.71),hyperlipidemia (OR 2.70,95％ CI 1.93-4.86),previous history of stroke or transient ischemic attack (OR 6.29,95％ CI 3.23-7.32),smoking (OR 4.80,95％ CI 2.18-6.19),and the TLR4 expression level before treatment (OR 3.28,95％ CI 2.87-6.93) were independently correlated with the lack of improvement in CVS,and cerebrospinal fluid replacement was independently correlated with CVS improvement (OR 0.40,95％ CI 0.14-0.89).There was no significant difference in the incidence of adverse reactions such as blood pressure drop,obstructive hydrocephalus and gastrointestinal hemorrhage betw een the observation group and the control group,but the incidence of delayed CVS (13.3％ vs.36.7％;x2 =7.510,P =0.006) and secondary cerebral infarction (8.3％ vs.31.7％;x2 =8.800,P =0.003) in the observation group were significantly lower than those of the observation group.Conclusion Nimodipine infusion combined with cerebrospinal fluid replacement by lumbar puncture affected the hemoglobin concentration and TLR4 expression levels,improved the CVS improvement rate,and significantly improved the clinical outcome in patients with CVS after aSAH.
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Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in diabetic rats. Methods One hundred and eighty healthy male Wistar rats, aged 3-4 months, weighing 260-310 g, were divided into 6 groups ( n=30 each) using a random number table method: op-eration group ( O group) , diabetes mellitus group ( DM group) , diabetic cognitive impairment group ( DCI group) , nimodipine plus operation group ( N+O group) , nimodipine plus diabetes mellitus group ( N+DM group) and nimodipine plus diabetic cognitive impairment group ( N+DCI group) . Diabetes mellitus model was established by intraperitoneal injection of streptozotocin 55 mg∕kg. Nimodipine 1 mg∕kg was intraperito-neally injected at 6 weeks after establishing the model in DCI and N+DCI groups and at 2 weeks after estab-lishing the model in DM and N+DM groups, and laparotomy was performed under sevoflurane anesthesia at 30 min after the end of administration. Morris water maze test was performed at 1 day before operation and 3 and 7 days after operation. Then rats were sacrificed, and hippocampal tissues were taken for determination of the apoptotic rate of neurons, cytoplasmic calcium concentrations ( by flow cytometry) and expression of caspase-3 in hippocampus ( by Western blot) . Results Compared with the baseline at 1 day before opera-tion, the escape latency was significantly prolonged, the number of crossing the original platform was re-duced, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were increased, and the expression of caspase-3 was up-regulated at each time point after operation in six groups ( P<0. 05 ) . Compared with group O, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were increased, and the expression of caspase-3 was up-regulated at each time point after operation in DM and DCI groups ( P<0. 05) . The escape latency was significantly shortened, the number of crossing the original platform was increased, the apoptotic rate of hippocampal neurons and cytosolic calcium concentrations were decreased, and the expression of caspase-3 was down-regulated at each time point after operation in group N+DM as compared with group DM and in group N+DCI as compared with group DCI ( P<0. 05) . Conclu-sion Nimodipine pretreatment can improve postoperative cognitive function in diabetic rats, and the mech-anism may be related to inhibiting calcium overload-induced apoptosis in neurons.
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Objective To evaluate the effect of nimodipine pretreatment on postoperative cognitive function in rats with chronic cerebral ischemia.Methods Sixty healthy male Sprague-Dawley rats,aged 3 months,weighing 250-350 g,were divided into 2 groups (n =30 each) using a random number table method:chronic cerebral ischemia operation group (group H) and nimodipine plus chronic cerebral ischemia operation group (group N+H).The chronic cerebral ischemia model was established by permanently ligating bilateral common carotid arteries of chloral hydrate-anesthetized rats.Rats underwent Morris water maze adaptive training for 5 days 2 weeks later.Nimodipine 1 mg/kg was intraperitoneally injected on 1st day after the end of adaptive training in group N+H,while the equal volume of normal saline was given instead in group H,and 30 min later splenectomy was performed under sevoflurane anesthesia in two groups.Ten rats in each group were selected on 1 day before operation and 3 and 7 days after operation and underwent Morris water maze test to assess cognitive function.The rats were then sacrificed,brains were removed,and hippocampal tissues were isolated for determination of apoptosis in hippocampal neurons and intracellular Ca2+concentrations([Ca2+]i) in cytoplasm and expression of Bcl-2 and Bax mRNA (by realtime polymerase chain reaction).The ratio of Bax mRNA to Bcl-2 mRNA was calculated.Results Compared with the baseline at 1 day before operation,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,the apoptotic rate and [Ca2+] i were increased,Bcl2 mRNA expression was down-regulated,and Bax mRNA expression was up-regulated,and Bax mRNA/Bcl-2 mRNA ratio was increased at each time point after operation in two groups (P＜0.05).Compared with group H,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,the apoptotic rate and [Ca2+]iwere decreased,Bcl-2 mRNA expression was up-regulated,and Bax mRNA expression was down-regulated,and Bax mRNA/Bcl-2 mRNA ratio was decreased at each time point after operation in group N+ H (P＜ 0.05).Conclusion Nimodipine pretreatment can improve the postoperative cognitive function of rats with chronic cerebral ischemia,and the mechanism may be related to inhibiting calcium overload-induced apoptosis in hippocampal neurons.
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Objective To evaluate the clinical efficacy and safety of nimodipine combine with butylphthalide in the treatment of patients with mild to moderate vascular cognitive impairment(VCI).Methods From January 2012 to December 2016,100 patients with mild to moderate VCI in Jinhua Municipal Central Hospital were randomly divided into control group(n =50) and treatment group(n =50) according to the random number table method.The control group received butylphthalide capsule,200 mg po tid.The treatment group received nimodipine tablets,40mg po tid,on the basis of the control group.The two groups of patients were treated for 24 weeks.Montreal cognitive assessment (MoCA),activities of daily living (ADL),serum hs-CRP,IL-6,TNF-α,clinical efficacy and adverse drug reactions were compared after treatment.Results After treatment,the scores of MoCA and ADL in the treatment group were (24.32 ± 2.87) points,(59.22 ± 6.17) points,respectively,which were significantly higher than those in the control group [(22.76 ± 2.67) points,(55.63 ± 6.3) points,t =2.814,2.870,all P ＜ 0.05].The effective rates in the treatment group and control group were 74.00％ (37/50),52.00％ (26/50),respectively,and there was statistically significant difference between the two groups (x2 =5.191,P ＜ 0.05).After treatment,the levels of hs-CRP [(189.51 ±23.27) mg/L vs.(211.51 ±25.51) mg/L],IL-6[(76.42 ±9.86) ng/L vs.(95.85 ± 10.23) ng/L],TNF-α[(0.24 ±0.08)ng/L vs.(0.32 ±0.10)ng/L] between the treatment group and the control group had statistically significant differences(t =4.505,9.670,4.417,all P ＜ 0.05).The adverse drug reactions were nausea and vomiting in 3 cases in the control group(6.00％),nausea and vomiting in 3 cases and hypotension in 1 case in the treatment group(8.00％),and there was no statistically significant difference between the two groups(P ＞0.05).Conclusion Nimodipine combined with butylphthalide in the treatment of mild to moderate VCI is effective and has high safety.