钙拮抗剂对大鼠脑缺血后血脑屏障通透性的影响

目的:探讨钙拮抗剂对大鼠脑缺血后血脑屏障(BBB)通透性的影响。方法:制备脑缺血再灌注(CIR)大鼠模型150只,在大鼠缺血2h后进行再灌注。将大鼠平均分为观察组(尼莫地平)与对照组(生理盐水),在6、12、24、48、72h时间点分别进行再灌注,观察每个时间点BBB通透性损伤情况及梗死灶体积百分比。结果:随着时间的延长,CIR后BBB通透性与梗死灶体积百分比出现逐步上升,且在12、48h达到双高峰。观察组的BBB通透性及脑梗死灶体积百分比的上升较对照组明显(P<0.05)。结论:CIR能够提升BBB的通透性,增加梗死灶体积百分比,而早期使用钙拮抗剂能够加重上述情况。

Effect of carotid artery stenting surgery combined with nimodipine on cerebral anterior circulation hemodynamics

Objective To evaluate the effect of carotid artery stenting combined with nimodipine on cerebral hemodynamics by comparing and analyzing the change of anterior cerebral blood flow before and after treatment through transcrania Doppler （TCD）. Methods Twenty patients with ischemic cerebrovascnlar disease were detected in blood flow velocity of bilateral middle cerebral arteries （MCA） and anterior cerebral arteries （ACA） and artery pulsatility index with TCD before and two weeks after treatment. Results After treatment, TCD examination showed dynamic changes in blood flow significantly, lpsilateral MCA flow velocity significantly increased; ipsilateral ACA flow velocity did not change significantly; there was no significant increase in the contralateral MCA flow velocity; flow rate decreased significantly in contralateral ACA. Conclusion Carotid artery stenting combined with nimodipine treatment can cause anterior cerebral hemodynamic changes in ipsilateral hemisphere and significantly improve blood flow

Efficacy of acupuncture in combination with medicine for mild cognitive impairment after cerebral infarction:a randomized controlled trial

Objective To observe the clinical effect of acupuncture in combination with medicine in the treatment of mild cognitive impairment after cerebral infarction as well as the impact on patients＇ daily living ability. Methods Seventy-two patients, in accordance with random number table, were divided into two groups, acupuncture combined with western medicine group （group A） and western medicine group （group B）, each group with 36 patients. In combination with nimodipine tablets, acupuncture which can regulate the mind and reinforce the intelligence [making Baihui （百会 GV 20）, Sishencong （四神聪EX-HN 1）, Sibai （四白 ST 2）, Fengchi （风池 GB 20）, Wanggu （完骨 GB 12）, Tianzhu （天柱 BL 10）, Shenmen （神门 HT 7）, Neiguan （内关 PC 6）, Shuigou （水沟 GV 26）, Sanyinjiao （三阴交 SP 6）, Taichong （太冲 LR 3）, Fenglong （丰隆 ST 40） as the main acupoints] was given in the treatment group （group A） while only nimodipine tablets were given in the control group （group B）. The efficacy of these two groups was evaluated by Montreal Cognitive Assessment （MoCA） Scale after the continuous treatment for three months. Results The remarkably effective rate was 69.4%.and the total effective rate was 91.7% in the treatment group, while the remarkably effective rate was 55.6% and the total effective rate was 80.6% in the control group; the differences between the two groups were statistically significant （P〈0.05）. When comparing the MoCA score before and after treatment, which was 20.23±4.67 before treatment and 26.84±3.87 after treatment in group A; 19.82±3.56 before treatment and 23.33±2.78 after treatment in group B, it was found that the score for both groups became higher after treatment than that before treatment. Furthermore, the increase of the score was higher in the treatment group （6.61±0.80） than that in the control group （3.51±0.78） and the differences were statistically significant （P〈0.05）. Conclusion Acupuncture, which can regulate the mind and reinforce the intelligence, combined with nimodipine tablets is an effective therapy for the treatment of mild cognitive impairment after cerebral infarction, which is superior to single treatment with nimodipine tablets.

Changes in and effective factors of microtubule associated protein 2 in traumatic neurons

Objective To investigate alterations in the microtubule-associated protein 2 (MAP-2) of neurons in Wistar rats and the effect of nimodipine (Nim), D-2-amino-5-phosphonovaleric acid (D-AP-5) and mild hypothermia on neuronal MAP-2 following fluid percussion injury (FPI).Methods Alterations of MAP-2 in Wistar rat neurons following FPI were measured by a confocal laserscanning microscope using MAP-2 immunofluorescence staining as a MAP-2 indicator.Results MAP-2 immunofluorescence staining was limited to the cell bodies and dendritic compartments of neurons and more intense in dendrites than in cell bodies. The loss of MAP-2 was marked at 3 h posttrauma ( P ＜ 0.01 ), and reached a maximum at 48 h post-trauma. Afterwards, fluorescence recovered partly at 72 h post-trauma. The application of Nim markedly reduced the loss of MAP-2 immunoreectivity within 1 h post-trauma ( P ＜ 0.01 ), and the application of D-AP-5 markedly reduced the loss of MAP-2immunoreactivity within 10 h post-injury ( P ＜ 0.01 ). The application of mild hypothermia decreased the loss of MAP-2 immunoreactivity within 1 h post-injury (P＜ 0.05).Conclusions The partial recovery of fluorescence at 72 h post-trauma indicate that the partial structure of the neuronal microtubules can be repaired by itself. Nim, D-AP-5 and mild hypothermia reduce the degradation of MAP-2 by different mechanisms. The treatment of neuronal cytoskeleton degradation following FPI must employ multiple therapeutic approaches.

Direct chiral separation of azelnidipine by HPLC with Pirkle-type column

Direct chiral separation of azelnidipine enantiomers with Pirkle-type Sumichiral OA-2500 column was studied by normal phase and reserve phase conditions. By normal phase, azelnidipine enantiomers were well separated with Rs as 4.0 using hexane–ethanol （90：10, v/v） as mobile phase, and Rs as 2.7 in shorter time （no more than 13 min） using hexane–ethanol （60：40, v/v） as the recommended mobile phase. They were only partially separated by reverse phase using methanol or methanol containing 0.05 mol/L ammonium acetate. Using same chiral column, the chiral separation of other dihydropyridine calcium antagonist analogues almodipine and nimodipine were also studied and showed partial chiral separation in normal phase.

HPLC determination of Nimodipine in plasma with an improved sample refining method and its application in pharmacokinetic studies

In order to prepare samples for HPLC analysis with maximum drug recovery and impurity elimination, a revised method for the extraction and purification of a target substance from plasma was developed and applied in a pharmacokinetic study with Nimodipine as a model drug. After protein precipitation of a plasma sample using pure methanol and evaporation of the supernatant to dryness, methanol of various concentrations from 10% to 100% were used to dissolve the remaining residues with the goal of maximizing drug recovery and impurity elimination. Through rigorous screening with HPLC peaks from residual impurity and recovered drug as the criteria, a methanol concentration of 30% was chosen. The standard curve was linear （r2〉 0.999） over the range of 2-160 ng/mL with a limit of quantification （LOQ） of 2 ng/mL. Intra- and inter-day precision values were below 15%, and the accuracy ranged from -1.70% to 5.88% at all three quality control （QC） levels. The wavelength of maximum absorption was 238 nm, and a smaller LOQ value of 2 ng/mL was achieved compared with the reported method. The revised method was successfully applied in a pharmacokinetic study of Nimodipine in rats and sample preparations of lidocaine hydrochloride.

Clinical observation on effect of scalp electroacupuncture for mild cognitive impairment

OBJECTIVE: To evaluate the therapeutic effect of scalp electroacupuncture for mild cognitive impairment (MCI) in the early stage. METHODS: Two hundred and thirty three MCI patients were randomly divided into three groups: the drug group, the scalp electroacupuncture group, and the syndrome differentiation group. For the scalp electroacupuncture group, the points of Baihui (DU 20), Sishecong (EX-HN1), Fengchi (GB 20), and Shenting (DU 24) were selected. For the syndrome differentiation group, specific acupoints were added on the basis of syndrome differentiation and according to the scale for the differentiation of syndromes in vascular dementia (SDSVD) beside the acupoints used in the scalp electroacupuncture group. For the drug group, nimodipine was orally administered. Each patient was treated for two courses, eight weeks. The score differences in minimental state examination (MMSE), picture recognition, and clock drawing test were observed before and after the treatment. RESULTS: After treatment, the score differences in MMSE and clock drawing test were of obvious statistical significance among three groups (P<0.01, P<0.05). The score differences in picture recognition were of extremely statistical significance between the scalp electroacupuncture group and the syndrome differentiation group (P<0.01), while the difference was not found in the drug group (P>0.05). There were statistical significant differences in therapeutic effects between the scalp electroacupuncture group and the drug group, and between the syndrome differentiation group and the drug group (P<0.05), while no statistical difference was found between scalp electroacupuncture group and the syndrome differentiation group (P>0.05). CONCLUSION: All the three therapies may improve the cognitive function of MCI patients. The therapeutic effects in the scalp electroacupuncture and syndrome differentiation groups were basically the same, but superior to nimodipine.

Clinical Effects of Acupuncture Combined with Nimodipine for Treatment of Vascular Dementia in 30 Cases

To study the therapeutic effects of acupuncture combined with nimodipine for vascular dementia. Methods： Acupuncture was applied at Baihui （GV 20）, Shenshu （BL 23）, Geshu （BL 17）, and the points selected according to the midnight-noon, ebb-flow eight methods of the intelligent turtle, combined with the drug nimodipine. The treatment was continued for 8 consecutive weeks. Results： Of the 30 cases treated, 6 cases were cured, 21 cases improved, and 3 cases failed, with a total effective rate of 90%. Conclusion： Acupuncture at Baihui （GV 20）, Shenshu （BL 23）, Geshu （BL 17）, and the points selected according to the midnight-noon, ebb-flow eight methods of the intelligent turtle combined with the drug nimodipine can yield definite therapeutic effects for vascular dementia.

Electroacupuncture on the Head Points for Improving Gnosia in Patients with Vascular Dementia

Objective： To investigate the clinical effects of electroacupuncture （EA） on the head points for improving gnosia in patients with vascular dementia （VD）. Methods： 90 VD patients were randomly divided into a drug group, an EA group and an EA plus drug group. Scoring with the M/VISE scale and detecting the relevant potentials were done before treatment and after a 6-week treatment. Results： Gnosia was improved after treatment in all the three groups with no significant difference by the intergroup comparison. Conclusion： The above three therapies can all improve gnosia, reduce the psychological stress, strengthen attention and shorten the awaiting time for recognition; and EA plus Nimodipine seems to be the best in the curative effect.

Neuroprotective effects of nimodipine and MK-801 on acute infectious brain edema induced by injection of pertussis bacilli to neocortex of rats

Objective: To explore the mechanism and type of acute infectious brain edema induced by injection of pertussis bacilli (PB) in rat neocortex, to study the neuroprotective effect of non-competitive antagonist of N-methl-D-aspartate ( NMDA ) receptor ( MK-801 ) and antagonist of Ca 2+ channels ( nimodipine )on brain edema, and to investigate the relationship between percentage of water content and cytosolic free calcium concentration ( i) in synaptosomes or content of Evans Blue (EB). Methods: 95 SD rats were randomly divided into five groups, ie, normal control group, sham-operated control group, PB group, nimodipine treatment group and MK-801 pretreatment group. The acute infectious brain edema was induced by injection of PB into the rats. Quantitative measurements of water content and the concentration of EB were performed. i was determined in calcium fluorescent indication Fura-2/AM loaded neuronal synaptosome with a spectrofluorophotometer. To observe the effect of MK-801 and nimodipine, we administered MK-801 48 hours and 24 hours before the injection of PB in MK-801 pretreatment group, and nimodipine after the injection of PB in nimodipine treatment group. The specific binding of NMDA receptor was measured with -MK-801 in the neuronal membrane of cerebral cortex. Results: The levels of water content and EB content of brain tissues, and i in the neuronal synaptosomes increased more significantly in the PB-injected cerebral hemisphere in the PB group than those of normal control group and sham-operated control group (P< 0.05). The water content and i increased with the duration of infectious brain edema. Nimodipine administered after the injection of PB could significantly decrease the water content, EB and i (P< 0.05). MK-801 could significantly decrease the water content, EB and i in 4 h and 24 h groups (P< 0.05). The Kd values were 30.5 nmol/L ±3.0 nmol/L and 42.1 nmol/L ±4.2 nmol/L in PB group and NS group respectively (P< 0.05), and Bmax were 0.606 pmol/mg.pro ±0.087 pmol/mg.pro and 0.623 pmol/mg.pro ±0.082 pmol/mg.pro respectively, without statistical significance (P> 0.05). Conclusions: The changes in the permeability of blood-brain barrier (BBB) and Ca 2+-overload may participate in the pathogenesis of infectious brain edema. Treatment with nimodipine can dramatically reduce the damage of brain edema and demonstrate neuroprotective effect on brain edema by inhibiting the excess of Ca 2+ influx and reducing the permeability of BBB. MK-801 pretreatment may inhibit the delayed Ca 2+ influx into the neurons. The infectious brain edema is not only cytotoxic brain edema (intracellular edema) but also vasogenic brain edema (extracellular edema) followed by earlier BBB breakdown, so infectious brain edema is complicated with brain edema.

Effects of nimodipine on changes of endothelin after head injury in rabbits

Objective: To investigate the effects of nimodipine on changes of endothelin after head injury. Methods: Sixty five adult rabbits were randomized into an injury group (IG, n=30), a nimodipine treatment group (NTG, n=30) and a control group (CG, n=5). With their heads unfixed, the animals in IG and NTG were injured in the frontal parietal zone with BIM II bioimpact. Blood samples and brain tissue were collected before and after injury. The endothelin level was measured with RIA. Results: The endothelin level in plasma and brain tissue was significantly increased 24 hours after injury. At the 8th or/and 24th hours postinjury, the endothelin level was significantly lower in NTG than that in IG. Conclusions: Nimodipine can prevent endothelin from elevation and act as a practical endothelin antagonist after head injury clinically.

Effects of Tongmai Huoxue Yin(通脉活血饮) on Tumor Necrosis Factor-alpha in the Acute Cerebral Ischemia Model Rat

Objective:To observe the interfering action of Tongmai Huoxue Yin(通脉活血饮) on the acute cerebral ischemia model rat.Methods:Total 60 SD rats,30 females and 30 males,were randomly divided into 4 groups,sham-operation group,model group,Nimodipine group and Tongmai Huoxue Yin group,15 rats in each group.The acute cerebral ischemia rat model was duplicated,the middle cerebral artery(MCA) were ligated and the thread was inserted for the rats in the model group,Nimodipine group and Tongmai Huoxue Yin group,for the rats in the sham-operation group,the arteries were separated without ligature and the thread was not inserted.After the modeling has succeed,the water-decocted concentrated solution of 20-fold Tongmai Huoxue Yin clinical dosage was intragastrically administrated in a dose of 3 mL /100 g · d divided into twice,1.5 mL /100 g once.Distilled water 3 mL /100 g·d was intragastrically administrated,1.5 mL /100 g once,for the rat in the model group,Nimodipne suspension 3 mL /100 g·d(0.6 mg /100 g) for the Nimodipine group and 3 mL /100 g · d(5.4g /100 g) for the Tongmai Huoxue Yin group,no drugs for the sham-operation group.And changes of tumor necrosis factor-alpha(TNF-α) contents in the serum and brain tissue were investigated.Results:Compared with the model group,compared with the sham-operation group,serum TNF-α content at 5 h of focal cerebral ischemic ischemia in the model group started to increase and reached to the high peak at 12 h,but in both the Tongmai Huoxue Yin group and the Nimodipine group decreased in varying degrees at the same time;compared with the sham-operation group,brain TNF-α content at 6 h of focal cerebral ischemic ischemia in the model group started to increase and reached to the high peak at 12 h,but in both the Tongmai Huoxue Yin group and the Nimodipine group decreased in varying degrees,with the most obviously decreased at 24 h of ischemia.Tongmai Huoxue Yin could significantly decrease TNF-α content in the brain tissue.Conclusion:Tongmai Huoxue Yin has a protective action on acute cerebral ischemia injury in the rat.

Nimodipine alleviates apoptosis-mediated impairments through the mitochondrial pathway after spinal cord injury

Abstract Spinal cord injury （SCI） remains an unsolved human health challenge. To alleviate the impairments of SCI, we studied the therapeutic effect of nimodipine （an L-type Ca^2＋ channel antagonist） on functional recovery from SCI using Nystrom＇s method in a mouse model. Eighty-four mice were divided into three groups： control group in which only vertebral plates were cut off without causing any spinal injuries; SCI; and SCI with nimodipine treatment. We assessed the histopathology, apoptosis detection, cell cycle, mitochondrial transmembrane potential, bcl-2/bax and caspase-3 levels of tissue 8 h, 1 d, 3 d and 4 d after trauma to evaluate rehabilitation. Behavioral performances were also assessed before and after nimodipine treatment. Results from inclined plane tests, motor score assessment and histological observations indicated that mice in the nimodipine-treated group rehabilitated better than those in the SCI group. The ratio of apoptosis, caspase-3 and bax expression in the nimodip- ine-treated group were significantly lower than those in the SCI group. The mitochondrial membrane potential and bcl-2 expression were up-regulated in the nimodipine-treated group. Taken together, our results indicate that the inhibition of calcium flux by nimodipine could reduce apoptosis processes and tissue damage through a mitochondrial pathway after spinal cord trauma [Current Zoology 57 （3）： 340-349, 2011].

Clinical Observation on 30 Cases of Vascular Dementia Treated by Acupuncture plus Kidney-Reinforcing Herbal Preparation

Objective： To investigate the therapeutic effect of acupuncture plus herbal medicine on vascular dementia （VD）. Methods： Thirty cases of vascular dementia were treated by acupuncture plus Chinese herbal medicine for 2 months, in comparison with western medication （Nimodipine） in the control group, to observe the evaluation value of Hasegawa Dementia Scale （HDS） before and after the treatments between the two groups, the clinical therapeutic effect and changes of plasma atrial natriuretic peptide （ANP） before and after the treatments between the two groups. Results and Conclusion： There were significant differences in intelligence and therapeutic effect between the two groups （P〈0.01） before and after the treatment, but the therapeutic effect was better in the acupuncture plus medicine group than in the western medication group. Judging from content of atrial natriuretic peptide, there was no significant difference between VD patients and normal adults before the treatment （P〉0.05）. Plasma ANP significantly increased in the acupuncture plus medicine group and western medicine group after the treatment （P〈0.01）, more remarkably in the acupuncture plus medicine group （P〈0.01）.

Controlled study of nimodipine in treatment of patients with diffuse axonal injury

Objective: To determine the efficacy and safety of early intervention with nimodipine treatment in diffuse axonal injury. Methods: Based on the characteristic radiological signs and criteria for diffuse axonal injury (DAI), 89 patients with the diagnosis of DAI were enrolled in this randomized, double blind, placebo controlled trial. Results: Nimodipine proved to be safe and well tolerated. With TCD sonography we found that there was a higher incidence of cerebral vasospasm in this series ( 38.2 %). Overall, Nimodipine produced a better clinical result than placebo, but there was no statistically significant difference in favorable outcome at 3 months after injury (P= 0.11 ) between the two groups. A trend toward a favorable effect was suggested by the analyses in two small subgroups, either in the patients suffering from clinical Grade Ⅲ DAI (P= 0.04 ), or in those with the TCD evidence of cerebral vasospasm during clinical observation (P= 0.049 ). Conclusions: We postulate that a clinically valuable benefit is possible with nimodipine treatment in DAI patients. However, the effects on outcome should be verified by further controlled study.

Therapeutic effect of nimodipine on experimental brain injury

Objective: To study the therapeutic effect of nimodipine on experimental brain injury. Methods: Experimental and control rabbits were subjected to a closed head injury. In one group nimodipine was given intravenously and the effect evaluated by electron microscopy, brain water content, calcium levels, transcranial Doppler, and intracranial pressure monitoring. Results: In rabbits treated with nimodipine the level of neuronal cytosolic free calcium was markedly decreased. There were less cellular damage and less spasm of the middle cerebral artery seen on electron microscopy. No difference regarding intracranial pressure changes between the two groups was noted. Conclusions: Nimodipine has a protective action on brain injury by blocking a series of pathological reactions induced by neuronal calcium overload, and by reducing the spasm of brain vessels and improving cerebral blood flow.

Clinical Observations on Acupuncture Treatment of 68 Migraine Patients

Objective To investigate the curative effect of points Fengchi（GB 20）, Tianzhu（BL 10） and Wangu （GB 12） on migraine. Methods. A treatment group of 68 patients received acupuncture of bilateral points Fengchi（GB 20）, Tianzhu（BL 10） and Wangu（GB 12） and a control group of 40 patients took orally Nimodipine and Oryzanol. The curative effect was evaluated in both groups after two courses of treatment. Results： The total efficacy rate was 92.7% and 72.5% and the control rate was 45.6% and 22.5%, respectively, in the two groups. Conclusion： Acupuncture is significantly more effective than Western medicine in treating migraine.