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Background: Acute spinal cord injury is a devastating condition typically affecting young people, mostly males. Steroid treatment in the early hours after the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life., Objectives: To review randomized trials of steroids for human acute spinal cord injury., Search Methods: We searched the Cochrane Injuries Group Specialised Register (searched 02 Aug 2011), The Cochrane Central Register of Controlled Trials 2011, issue 3 (The Cochrane Library), MEDLINE (Ovid) 1948 to July Week 3 2011, EMBASE (Ovid) 1974 to 2011 week 17, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) 1970 to Aug 2011, ISI Web of Science: Conference Proceedings Citation Index- Science (CPCI-S) 1990 to Aug 2011 and PubMed [www.ncbi.nlm.nih.gov/sites/entrez/] (searched 04 Aug 2011) for records added to PubMed in the last 90 days). Files of the National Acute Spinal Cord Injury Study (NASCIS) were reviewed (NASCIS was founded in 1977 and has tracked trials in this area since that date). We also searched the reference lists of relevant studies and previously published reviews., Selection Criteria: All randomized controlled trials of steroid treatment for acute spinal cord injury in any language., Data Collection and Analysis: One review author extracted data from trial reports. Japanese and French studies were found through NASCIS and additional data (e.g. SDs) were obtained from the original study authors., Main Results: Eight trials are included in this review, seven used methylprednisolone. Methylprednisolone sodium succinate has been shown to improve neurologic outcome up to one year post-injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg over 15 minutes, with maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial results were replicated in a Japanese trial but not in the one from France. Data was obtained from the latter studies to permit appropriate meta-analysis of all three trials. This indicated significant recovery in motor function after methylprednisolone therapy, when administration commenced within eight hours of injury. A more recent trial indicates that, if methylprednisolone therapy is given for an additional 24 hours (a total of 48 hours), additional improvement in motor neurologic function and functional status are observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries. A modified regimen was found to improve recovery after surgery for lumbar disc disease. The risk of bias was low in the largest methyprednisolne trials. Overall, there was no evidence of significantly increased complications or mortality from the 23 or 48 hour therapy., Authors' Conclusions: High-dose methylprednisolone steroid therapy is the only pharmacologic therapy shown to have efficacy in a phase three randomized trial when administered within eight hours of injury. One trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours, if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacologic therapy for acute spinal cord injury.

Background and Purpose: To investigate the effect of locally applied nimodipine prolonged-release microparticles on angiographic vasospasm and secondary brain injury after experimental subarachnoid hemorrhage (SAH)., Methods: 70 male Wistar rats were categorized into three groups: 1) sham operated animals (control), 2) animals with SAH only (control) and the 3) treatment group. SAH was induced using the double hemorrhage model. The treatment group received different concentrations (20%, 30% or 40%) of nimodipine microparticles. Angiographic vasospasm was assessed 5 days later using digital subtraction angiography (DSA). Histological analysis of frozen sections was performed using H&E-staining as well as Iba1 and MAP2 immunohistochemistry., Results: DSA images were sufficient for assessment in 42 animals. Severe angiographic vasospasm was present in group 2 (SAH only), as compared to the sham operated group (p<0.001). Only animals within group 3 and the highest nimodipine microparticles concentration (40%) as well as group 1 (sham) demonstrated the largest intracranial artery diameters. Variation in vessel calibers, however, did not result in differences in Iba-1 or MAP2 expression, i.e. in histological findings for secondary brain injury., Conclusions: Local delivery of high-dose nimodipine prolonged-release microparticles at high concentration resulted in significant reduction in angiographic vasospasm after experimental SAH and with no histological signs for matrix toxicity.

Primary thunderclap headache (TCH) is a rare condition, of which the onset can be triggered by coughing, exercise, and sexual activity. Micturition is a recognized trigger of secondary TCH with pheochromocytoma in bladder, but not of primary TCH. We describe a patient with an apparent primary TCH, which repeatedly occurred immediately after micturition until she achieved a therapeutic dosage of nimodipine.

Objective: Despite dramatic advances in all medical era, cerebral vasospasm is still the major complication in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to assess the influence of intraarterial (IA) nimodipine in the treatment of symptomatic vasospasm and in preventing neurological disabilities., Materials and Methods: We retrospectively reviewed 10 patients of SAH who received IA nimodipine in 15 procedures. The decision to perform angiography and endovascular treatment was based on the neurological examination, brain computed tomography (CT) and CT-angiography. The procedure reports, anesthesia records, neurological examination before and after the procedure, brain imaging and short- and long-term outcome were studied., Results: The average dose of nimodipine was 2 mg. The median change in mean arterial pressure at 10 min was -10 mmHg. No significant change of heart rate was observed at 10 min. There was radiological improvement in 80% of the procedures. Neurological improvement was noted after eight out of 12 procedures when nimodipine was used as the sole treatment and after 10 out of 15, overall. Six patients clinically improved after the treatment and had good outcome. In one patient, an embolus caused fatal anterior and middle cerebral arteries infarction. There was no other neurological deficit or radiological abnormality due to the nimodipine treatment itself., Conclusion: Low-dose IA nimodipine is a valid adjunct for the endovascular treatment of cerebral vasospasm. Beneficial effects are achieved in some patients, prompting a prospective control study.

Objective: To explore the network control mechanism of the calcium signaling pathway in cerebral ischemic injury after intervention by the main components of Qingkailing (see text), i.e. Baicalin, Jasminoidin and their combination., Methods: Thirty mice were randomly divided into 5 groups, a baicalin group, a Jasminoidin group, a baicalin plus Jasminoidin group, a nimodipine group, and a model group (n = 6). The global cerebral ischemia-reperfusion mouse model was established. The mice were administrated respectively by injection of baicalin, Jasminoidin, mixture of baicalin and Jasminoidin, and nimodipine into the caudal vein, with the model group given no any drug. Three hours after operation, the brain was removed and sectioned. After calculation of cerebral ischemic area by 2,3,5-triphenyltetrazolium staining, the percentage of infarct volume was calculated. The total RNA of the mouse brain tissue was extracted to obtain the whole genome expression profile, and the differentially expressed genes related to the calcium signaling pathway was analyzed with Bayesian network structures., Results: Compared with the model group, the ischemic area was significantly reduced in the baicalin group, the Jasminoidin group, the Baicalin plus Jasminoidin group (all P < 0.05). The ischemic area in the baicalin plus Jasminoidin group was smaller than the other three groups (all P < 0.01). In the gene regulatory network structures of calcium signaling pathway, the average length and equitability were the highest in the baicalin plus Jasminoidin group, followed by the nimodipine group., Conclusion: Compared with a single component, combination of Baicalin and Jasminoidin can more obviously intervene in the overall expression of calcium signaling pathway, and the mechanism is related with the aggregation characteristic of the gene expression network.

Objectives: To determine if the age of packed red blood cells (PRBCs) is associated with adverse events or outcomes in patients with subarachnoid haemorrhage (SAH)., Aim: Analyse data on PRBC age to complications and outcomes in patients with SAH., Background: Patients who receive a PRBC transfusion after SAH have a higher rate of complications, and older PRBC age may be responsible for this., Methods/materials: We prospectively recorded clinical and demographic data, acute adverse effects related to transfusion, major hospital events, radiographic cerebral infarction, PRBC age and outcomes in 119 patients with SAH who received a PRBC transfusion. Patients were followed for outcomes at 14 days or discharge, 28 days and 3 months with the modified Rankin scale (a measure of neurologic function)., Results: In 241 PRBC transfusions, there was new fever in 36 (15%), hypotension in 23 (10%), pulmonary oedema or symptomatic respiratory distress in 5 (2%) and rash in 1 (1%). Age of PRBCs administered was not associated with vasospasm, cerebral infarction, acute adverse events or outcomes (P > 0·1 for all)., Conclusions: In this small registry of patients with SAH, the age of transfused PRBCs was not associated with adverse events or outcomes., (© 2010 The Authors. Transfusion Medicine © 2010 British Blood Transfusion Society.)

Purpose: To better characterize postpartum cerebral angiitis (PPCA)., Methods: We present a case of PPCA in which a 34-year-old G6P5104 underwent a normal vaginal delivery and developed PPCA. She had no signs or symptoms of gestational hypertension or preeclampsia. She had a history of migraines and received methylergonovine at delivery. She represented postpartum with headache and hypertension. The patient had characteristic findings of cerebral angiitis on imaging, and was diagnosed with PPCA. She was treated with nimodipine and steroids. She was monitored with transcranial Dopplers., Results: In reviewing the literature, we found 23 cases of PPCA. We found that none had proteinuria, most were hypertensive, and all presented with headache., Conclusions: Use of sympathomimetic agents, particularly among those with migraines, may increase risk of PPCA.

The present study focuses on the temporal calcium significance in middle cerebral artery occluded (2 h ischemia)-reperfused (70 h reperfusion) rats treated with nimodipine (NM) through concurrent measurements of excitotoxicity, bioenergetics and neurobehavioural paradigms. Further, the suitable therapeutic time window of calcium channel antagonism in stroke was also ascertained. NM (5 mg/kg, i.p.) was administered at pre (30 min before the induction of ischemia), during (1 h following occlusion of MCA) and post-ischemic (3 h after begin of reperfusion) states. The magnitude of neuroprotection in terms of excitotoxicity (glutamate, glutamine synthetase, Na(+)K(+)ATPase), bioenergetics (ATP, NAD(+)) and neurobehavioural paradigms (neurological score and open field exploratory behaviour) were measured and compared to ensure the therapeutic time-window of NM in stroke. Middle cerebral artery occlusion-reperfusion (MCAO/R) was found to elevate glutamate, glutamine synthetase levels and deplete Na(+)K(+)ATPase activity in the vehicle treated group (IR group). Significant decrease in bioenergetics such as ATP and NAD(+) levels was also observed. Further, IR group demonstrated grievous oxidative stress (increase in lipid peroxidation, protein carbonyl content, nitrite/nitrate levels and decrease in superoxide dismutase and glutathione levels) along with anxiogenic behaviour, neurological deficits and neuronal damage and decreased nuclear to cytoplasm ratio in CA1 hippocampal region. Post-ischemic NM administration reversed the excitotoxicity, neurobehavioural and histopathological alterations significantly, but it restored bioenergetics level in MCAO/R rats only partially. These findings were further confirmed with the combination treatment (CT) of post-ischemic NM and pre-ischemic memantine (MN) administration, since MN showed protective effect in the pre-ischemic administration (Babu and Ramanathan, 2009). The failure of NM to forefend the neurodegeneration on pre- and during-ischemic administration suggests that the initial phase damages in ischemic-reperfusion (IR) might be mediated through other mechanism(s) such as glutamergic overstimulation or reverse operation of glutamate transporters. From the present study, it is concluded that calcium plays a crucial role in post-ischemic status and the suitable therapeutic time window of calcium antagonism is the post-ischemic state., (Copyright © 2010 ISDN. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the effects of nimodipine on symptomatic cerebral vasospasm in rabbits., Methods: Twenty four japanese white rabbits which ligation of bilateral common carotid arteries and no neurological deficits were randomized to sham-operation, subarachnoid hemorrhage (SAH) and nimodipine which injected of nimodipine 0.1 mg/kg, continuous vein administration 5 day. The behavior scores, neurological scores were observed everyday and cerebral angiography changes were measured twice by 3D-CTA, and basilar artery was removed for pathological examination after last CTA examination., Results: In SAH group, The basilar artery were significantly vasoconstrictive on 5 days, neurological scores were increased, and the basilar artery was found apoptosis-like changes under light microscopic and electron microscope. Nimodipine group could not dilated the basilar artery arteriospasm after SAH, but it could attenuate neurological deficit, and obviously alleviate the pathological changes of basilar artery., Conclusion: Nimodipine could not vasodilation of basilar artery in SCVS, but obviously could alleviate neurological changes and pathological changes of basilar artery in rabbits with symptomatic cerebral vasospasm.

Background: the aim of this study was to assess and to compare the ability of intrathecal flunarizine and nimodipine to prevent vasospasm in a rabbit model of subarachnoid hemorrhage (SAH)., Method: forty male New Zealand white rabbits were allocated into 5 groups randomly. The treatment groups were as follows: (1) control (no SAH [n = 8]), (2) SAH only (n = 8), (3) SAH plus vehicle (n = 8), (4) SAH plus nimodipine (n = 8), and (5) SAH plus flunarizine (n = 8). Before sacrifice, all animals underwent femoral artery catheterization procedure by open surgery under anesthesia and angiography performed for each animal., Findings: there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 5 were significantly higher than in group 2 (p < 0.05).Basilar artery vessel diameter and basilar artery luminal section areas in group 5 were significantly higher than in group 4 (p < 0.05)., Conclusions: these findings demonstrate that flunarizine has marked vasodilatatory effect in an experimental model of SAH in rabbits.

Background: cerebral vasospasm (CVS) is one of the most considerable complications of subarachnoid hemorrhage (SAH). The aim of this study was to assess and to compare the ability of intrathecal dotarizine and nimodipine to prevent and treat vasospasm in a rabbit model of subarachnoid hemorrhage., Method: thirty male New Zealand white rabbits weighing 2,500-3,000 g were allocated into five groups randomly. The treatment groups were as follows: Control, only SAH, SAH/Dotarizine, SAH/Nimodipine, SAH/Vehicle. Forty-eight hours after SAH injection, all animals underwent femoral artery catheterization procedure by open surgery under anesthesia and angiography performed for each animal in the fifth day just before sacrifice., Findings: basilar artery vessel diameters are measured by angiography. Basilar artery vessel diameters and luminal sectional areas are measured in pathology slides. There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05)., Conclusions: these findings demonstrate that calcium channel blocker dotarizine has marked vasodilatory effect in an experimental model of SAH in rabbits. Nimodipine is an effect-proven agent in CVS, but dotarizine may take place of it.

Objective: to investigate the influence of pre-operative conditions and microsurgical skill on the post-operative outcomes of intracranial aneurysms by retrospective analysis of 120 cases with microsurgical treatment., Methods: 120 patients with 134 intracranial aneurysms received microsurgical treatment via pterional approach or improved pterional approach., Results: of 134 aneurysms, 122 were clipped, one was coated, three were isolated and there was parent artery deligation in one case. 111 Patients were cured, seven cases gave up therapy post-operation, and two died. According to GOS standard, the outcome in the discharge stage was good in 94 cases, mild disability in 12 cases, moderate disability in three cases and severe disability in two cases. Long-term follow-up was performed in all patients, of whom 95 recovered well, mild disability in 12 cases, moderate disability in two cases and severe disability in one case., Conclusion: surgical clipping was the most effective method to treat intracranial aneurysm. Optimal chance and microsurgical technique, as well as microanatomical knowledge, are keys for successful treatment.

Objective: intrathecal administration of calcium channel antagonists has been proposed to reduce cerebral vasospasm (CVS) in animal subarachnoid hemorrhage (SAH) models. Also, delayed CVS treatment model with oral administration of cilostazol can be seen in the literature., Methods: in this study, 25 male New Zealand white rabbits were randomly assigned to five groups: control, SAH only, SAH/nimodipine, SAH/cilostazol, SAH/vehicle. The animals' basilar arteries were sectioned from four separate zones and four sections were obtained from each rabbit. Basilar artery luminal section areas were measured by using SPOT for windows Version 4.1 computer program., Results: basilar artery luminal section areas in SAH/ nimodipine and SAH/ cilostazol groups were significantly higher than SAH only group (P < 0.05)., Conclusion: phosphodiesterase 3 inhibitor cilostazol has vasodilatory effects without affecting cerebral blood flow. Nimodipine is a calcium channel blocker and is still used in vasospasm therapy either oral or intravenously. This study demonstrates that prophylactic bolus intrathecal administration of either cilostazol or nimodipine equally prevents SAH-associated CVS in an animal model. We therefore propose that cilostazol is a candidate for clinical trials in the treatment of delayed vasospasm.

Background: the aim of this study was to assess and to compare the ability of intrathecal nicergoline and nimodipine in prevention of cerebral vasospasm in a rabbit model of subarachnoid hemorrhage (SAH)., Method: twenty male New Zealand white rabbits were allocated into four groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) control [no SAH (n = 5)], (2) SAH only (n = 5), (3) SAH plus nimodipine (n = 5), and (4) SAH plus nicergoline (n = 5)., Findings: there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 3 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). There was no significant difference between basilar artery vessel diameter and basilar artery luminal section areas in group 3 and group 4., Conclusions: these findings demonstrate that intrathecal nicergoline has a vasodilatatory effect in an experimental model of SAH in rabbits but not more than that of nimodipine.

Today our knowledge of the choroidal circulation is limited: we know its anatomy, but, on the other hand, its physiopathology remains to be fully. The choroid is involved in a number of important ocular diseases. The Laser Doppler Flowmetry (LDF) is a technique that allows non-invasive measurement of haemodynamic parameters of the subfoveal choroidal circulation. It is easy to use in daily clinic activity. The aim of this mini-review is to describe LDF studies of the choroidal circulation performed in healthy subjects under different environmental conditions, in subjects with ocular diseases, as well as studies of the effects of various drugs can induce on this circulation.

The vascular remodeling associated with hypertension involves oxidative stress and enhanced matrix metalloproteinases (MMPs) expression/activity, especially MMP-2. While previous work showed that lercanidipine, a third-generation dihydropyridine calcium channel blocker (CCB), attenuated the oxidative stress and increased MMP-2 expression/activity in two-kidney, one-clip (2K1C) hypertension, no previous study has examined whether first- or second-generation dihydropyridines produce similar effects. We compared the effects of nifedipine, nimodipine, and amlodipine on 2K1C hypertension-induced changes in systolic blood pressure (SBP), vascular remodeling, oxidative stress, and MMPs levels/activity. Sham-operated and 2K1C rats were treated with water, nifedipine 10 mg/kg/day, nimodipine 15 mg/kg/day, or amlodipine 10 mg/kg/day by gavage, starting 3 weeks after hypertension was induced. SBP was monitored weekly. After 6 weeks of treatment, quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin-stained sections. Aortic and systemic reactive oxygen species levels were measured by using dihydroethidine and thiobarbituric acid-reactive substances (TBARs), respectively. Aortic MMP-2 levels and activity were determined by gelatin zymography, in situ zymography, and immunofluorescence. Nifedipine, nimodipine, or amlodipine attenuated the increases in SBP in hypertensive rats by approximately 17% (P < 0.05) and prevented vascular hypertrophy (P < 0.05). These CCBs blunted 2K1C-induced increases in vascular oxidative stress and plasma TBARs concentrations (P < 0.05). All dihydropyridines attenuated the increases in aortic MMP-2 levels and activity associated with 2K1C hypertension. These findings suggest lack of superiority of one particular dihydropyridine, at least with respect to antioxidant effects, MMPs downregulation, and inhibition of vascular remodeling in hypertension.

Reversible cerebral vasoconstriction is a rare and poorly understood syndrome, without clear diagnostic criteria. It has been described in association with multiple disorders, but has only been reported rarely in the setting of carotid artery dissection and, to our knowledge, never before in association with renal artery stenosis.

We present the first case of a 57 year old man who developed severe, acute vasospasm following transcallosal resection of an unusual, xanthogranulomatous colloid cyst. The 16 year history of growth of this cyst may have resulted in its unusual pathology, and the subsequent vasospastic reaction to its excision. We discuss the potential pathological relationship between the inflammatory nature of the cyst, chemical meningitis and vasospasm, and what this implies about vasospasm in general. The severe, life-threatening vasospasm affected all four major vessels and required aggressive management by endovascular injection of nimodipine and angioplasty, with good recovery. The case illustrates a previously undescribed sequel of surgery for this condition, demonstrates an effective treatment and offers possible insights into the pathogenesis of vasospasm., (Copyright 2010 Elsevier B.V. All rights reserved.)

Recent literature contains many reports of value to clinicians providing anesthetic or intensive care for neurosurgical patients or patients experiencing, or at risk for, neurological impairment. We will review many of these articles, focusing on those that address intracranial hemorrhage, intracranial procedures, carotid endarterectomy, spine surgery, and the determinants of outcome in patients with evolving or new-onset neurologic disease. Additionally, we will review articles addressing neurotoxicity, neuroprotection, and nervous system monitoring.

Aneurysmal subarachnoid hemorrhage (SAH) accounts for a significant percentage of morbidity and mortality among patients admitted to neurosurgical centers throughout the world. Even for individuals surviving beyond the initial presentation and intervention for aneurysmal SAH, the occurrence of cerebral vasospasm has the potential to induce a second tier of complications that can be just as devastating as the inciting event. However, despite numerous studies and some initial advancements in management, therapeutic modalities are limited to help prevent or treat this complex entity. Historically, the mainstay of treatment for cerebral vasospasm has been a combination of hypervolemia, hemodilution, and hypertension. In addition, other systemic therapies such as oral nimodipine, statins, and intravenous magnesium, as well as intensive glucose control, appear to have some promise, although they are limited at times by adverse effects. To avoid these adverse consequences and perhaps gain some modicum of efficacy, attempts have been made to use endovascular techniques to physically dilate vessels or to administer drugs directly to the site of action and thus avoid many of the untoward effects of systemic pharmacotherapy. Controversy still remains over the success of intraarterial therapy, the drugs or techniques to be used, and the best timing of this therapy. Based on the currently available literature, it is impossible to assess the most effective intraarterial therapy. Randomized controlled trials that can control for baseline factors and technical expertise are needed to provide more conclusive data. Clinical pharmacists should be actively involved in assisting interventional radiologists and neurosurgeons in providing safe and appropriate pharmacotherapy in this promising but controversial arena of intraarterial drug delivery.

Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity. Leukocyte sequestration further decreased perfusion by narrowing luminal diameters in the affected vessels and blocking capillaries. Remarkably, vascular collapse at various degrees was observed in 44% of mice with CM, which also presented more severe vasoconstriction. Coadministration of artemether and nimodipine, a calcium channel blocker used to treat postsubarachnoid hemorrhage vasospasm, to mice presenting CM markedly increased survival compared with artemether plus vehicle only. Administration of nimodipine induced vasodilation and increased pial blood flow. We conclude that vasoconstriction and vascular collapse play a role in murine CM pathogenesis and nimodipine holds potential as adjunctive therapy for CM.

Background: Delayed cerebral ischaemia is a significant contributor to poor outcome (death or disability) in patients with aneurysmal subarachnoid haemorrhage (SAH). Tirilazad is considered to have neuroprotective properties in animal models of acute cerebral ischaemia., Objectives: To assess the efficacy and safety of tirilazad in patients with aneurysmal SAH., Search Strategy: We searched the Cochrane Stroke Group Trials Register (last searched October 2009); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009); MEDLINE (1966 to October 2009); EMBASE (1980 to October 2009); and the Stroke Trials Directory, the National Center for Complementary and Alternative Medicine, and the National Institute of Health Clinical Trials Database (searched October 2009). We handsearched 10 Chinese journals, searched the reference lists of relevant publications, and contacted the manufacturers of tirilazad., Selection Criteria: Randomised trials of tirilazad started within four days of SAH onset, compared with placebo or open control in patients with aneurysmal SAH documented by angiography and computerised tomography (CT) scan or cerebrospinal fluid examination, or both., Data Collection and Analysis: We extracted data relating to case fatality, poor outcome (death, vegetative state, or severe disability), delayed cerebral ischaemia (or symptomatic vasospasm), cerebral infarction and adverse events of treatments. We pooled the data using the Peto fixed-effect method for dichotomous data., Main Results: We included five double-blind, placebo-controlled trials involving 3821 patients; there was no significant heterogeneity. Oral or intravenous nimodipine was used routinely as a background treatment in both groups in all trials. There was no significant difference between the two groups at the end of follow up for the primary outcome, death (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.74 to 1.06), or in poor outcome (death, vegetative state or severe disability) (OR 1.04, 95% CI 0.90 to 1.21). During the treatment period, fewer patients developed delayed cerebral ischaemia in the tirilazad group than in the control group (OR 0.80, 95% CI 0.69 to 0.93). Subgroup analyses did not demonstrate any significant difference in effects of tirilazad on clinical outcomes. Leukocytosis and prolongation of Q-T interval occurred significantly more frequently in the treatment group in only one trial evaluating tirilazad at high dose. There was no significant difference in infusion site disorders or other laboratory parameters between the two groups., Authors' Conclusions: There is no evidence that tirilazad, in addition to nimodipine, reduces mortality or improves poor outcome in patients with aneurysmal SAH.

Dopamine deficiency associated with Parkinson's disease (PD) results in numerous changes in striatal transmitter function and neuron morphology. Specifically, there is marked atrophy of dendrites and dendritic spines on striatal medium spiny neurons (MSN), primary targets of inputs from nigral dopamine and cortical glutamate neurons, in advanced PD and rodent models of severe dopamine depletion. Dendritic spine loss occurs via dysregulation of intraspine Cav1.3 L-type Ca(2+)channels and can be prevented, in animal models, by administration of the calcium channel antagonist, nimodipine. The impact of MSN dendritic spine loss in the parkinsonian striatum on dopamine neuron graft therapy remains unexamined. Using unilaterally parkinsonian Sprague-Dawley rats, we tested the hypothesis that MSN dendritic spine preservation through administration of nimodipine would result in improved therapeutic benefit and diminished graft-induced behavioral abnormalities in rats grafted with embryonic ventral midbrain cells. Analysis of rotational asymmetry and spontaneous forelimb use in the cylinder task found no significant effect of dendritic spine preservation in grafted rats. However, analyses of vibrissae-induced forelimb use, levodopa-induced dyskinesias and graft-induced dyskinesias showed significant improvement in rats with dopamine grafts associated with preserved striatal dendritic spine density. Nimodipine treatment in this model did not impact dopamine graft survival but allowed for increased graft reinnervation of striatum. Taken together, these results demonstrate that even with grafting suboptimal numbers of cells, maintaining normal spine density on target MSNs results in overall superior behavioral efficacy of dopamine grafts.

Organophosphorus (OP) used as pesticides and hydraulic fluids can produce acute poisoning known as OP-induced delayed neuropathy (OPIDN), whose effects take long time to recover. Thus a secure therapeutic strategy to prevent the most serious effects of this poisoning would be welcome. In this study, tri-o-cresyl phosphate (TOCP, 500 mg/kg p.o.) was given to hens, followed or not by nimodipine (1mg/kg i.m.) and calcium gluconate (Ca-glu 5mg/kg i.v.). Six hours after TOCP intoxication, neuropathy target esterase (NTE) activity inhibition was observed, peaking after 24h exceeding 80% inhibition. A fall in the plasmatic calcium levels was noted 12h after TOCP was given and, in the sciatic nerve, Ca(2+) fell 56.4% 24h later; at the same time calcium activated neutral protease (CANP) activity increased 308.7%, an effect that lasted 14 days. Any bird that received therapeutic treatment after TOCP intoxication presented significant signs of OPIDN. These results suggest that NTE may be implicated in the regulation of calcium entrance into cells being responsible for the maintenance of normal function of calcium channels, and that increasing CANP activity is responsible to triggering OPIDN. Thus, with one suitably adjusted dose of nimodipine as well as Ca-glu, we believe that this treatment strategy may be used in humans with acute poisoning by neuropathic OP., (2009 Elsevier Ireland Ltd. All rights reserved.)

Based on the outcomes of surgical management of thirty-six patients diagnosed with atherosclerosis of carotid arteries and a further thirty-five 35 patients presenting with atherosclerotic lesions of the subclavian and vertebral arteries the authors substantiated a differentiated therapeutic policy aimed at protecting the brain from ischaemia, having demonstrated efficiency of cerebral protection with nimodipine and rheopolyglukin in patients subjected to operations on the subclavian and vertebral arteries and feasibility of combining this method with the application of a temporary puncture carotid-artery bypass graft during carotid endarterectomy. Functional possibilities of puncture-mediated bypass grafting of the carotid artery was confirmed by studying the blood flow in the common, internal carotid and median cerebral arteries on the operated side and ipsilateral side in patients with and without a bypass graft applied.

Objective: To establish whether nimodipine, a calcium channel blocker, accelerates or otherwise improves functional recovery of whisking after facial nerve crush injury in the rat., Methods: Thirty rats underwent exposure of the left main trunk of the facial nerve followed by a standard crush injury and subsequent quantitative facial movement testing. Animals were randomized into an experimental group (n = 15) and a control group (n = 15). Four days prior to facial nerve manipulation, experimental animals underwent subcutaneous implantation of a nimodipine-secreting pellet. All animals were tested preoperatively and on postoperative days 2, 8 to 17, 20, 22, 24, and 31 using a validated, quantitative whisking kinematics apparatus. Whisks were analyzed for amplitude, velocity, and acceleration., Results: Animals receiving nimodipine demonstrated significantly better whisking on 5 days (postoperative days 9, 11 to 13, and 20) compared with control animals (P < .001, P = .003, P = .009, P = .009, and P = .009, respectively; 1-tailed ttest). Overall, the nimodipine-treated animals showed earlier recovery compared with the untreated animals., Conclusions: We demonstrate that nimodipine improves recovery of whisking after facial nerve crush. This finding corroborates the semiquantitative findings of others, and provides complete whisking kinematic data on its effects. Given the low adverse effect profile of nimodipine, there may be clinical implications in its administration in patients experiencing facial nerve injury.

Reversible cerebral vasoconstriction syndrome is characterised by severe headaches with or without seizures and focal neurological deficits, and constriction of cerebral arteries which resolves spontaneously in 1-3 months. It affects females slightly more than males, and mean age of onset is around 45 years. Approximately 60% of cases are secondary, mainly postpartum and after exposure to vasoactive substances. The major complications are localised cortical subarachnoid haemorrhage (22%) and parenchymal ischaemic or haemorrhagic strokes (7%) which may leave permanent sequelae. Diagnosis requires the demonstration of the "string of beads" appearance of cerebral arteries on angiography, with complete or almost complete resolution on repeat angiography 12 weeks after onset. Nimodipine seems to reduce thunderclap headaches within 48 h but has no definite effect on the haemorrhagic and ischaemic complications.

Object: Intraoperative neurophysiological monitoring has become an integral part of vestibular schwannoma surgery. The aim of this article was to review the different techniques of intraoperative neurophysiological monitoring in vestibular schwannoma surgery, identify the clinical impact of certain pathognomonic patterns on postoperative outcomes of facial nerve function and hearing preservation, and highlight the role of postoperative medications in improving delayed cranial nerve dysfunction in the different reported series., Methods: The authors performed a review of the literature regarding intraoperative monitoring in acoustic/vestibular schwannoma surgery. The different clinical series representing different monitoring techniques were reviewed. All the data from clinical series were analyzed in a comprehensive and comparative model., Results: Intraoperative brainstem auditory evoked potential monitoring, direct cochlear nerve action potential monitoring, and facial nerve electromyography are the main tools used to assess the functional integrity of an anatomically intact cranial nerve. The identification of pathognomonic brainstem auditory evoked potential and electromyography patterns has been correlated with postoperative functional outcome. Recently, perioperative administration of intravenous hydroxyethyl starch and nimodipine as vasoactive and neuroprotective agents was shown to improve vestibular schwannoma functional outcome in few reported studies., Conclusions: Recent advances in electrophysiological technology have considerably contributed to improvement in functional outcome of vestibular neuroma surgery in terms of hearing preservation and facial nerve paresis. Perioperative intravenous nimodipine and hydroxyethyl starch may be valuable additions to surgery.

Objective: 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.

Ultralow doses of antibodies to S-100 protein increased rat survival, reduced neurological deficit, eliminated myorelaxation, and improved movement coordination and cognitive functions in rats with experimental hemorrhagic stroke; the efficiency of the preparation was not inferior to that of nimodipine. In contrast to nimodipine, ultralow doses of antibodies to S-100 protein exhibited pronounced anxiolytic properties.

Objectives: Following perioperative injury to a macroscopically intact recurrent laryngeal nerve (RLN), there are two possible intraneural injury types: 1) axonal injury, including disruption of axons, and 2) conduction block, only affecting the Schwann cells and the nodes of Ranvier. In this study, it was hypothesized that the functional outcome after RLN injury may depend on the type of nerve injury., Methods: Fifteen patients with acute postoperative unilateral RLN paralysis were prospectively studied. Electrophysiological examination (laryngeal electromyography) was used to differentiate between the two types of nerve injury. Vocal fold motions were monitored by repeated laryngoscopy during the study period (up to 6 months). Three of the patients with axonal injury were treated with the regeneration-promoting agent nimodipine., Results: The patients with conduction block all recovered normal vocal fold motion, whereas patients with axonal injury within the nerve had a significantly worse outcome. The 3 patients who were treated with nimodipine all recovered normal or near-normal vocal fold mobility despite the more severe axonal injury., Conclusions: In contrast to previous reports, our results show that laryngeal electromyography is a reliable tool for diagnosing the type of injury within the injured RLN, making it possible to predict the functional outcome in these patients. On the basis of the results, a future randomized study on nimodipine treatment for RLN axonal injury is suggested.

Introduction: The vast amount of literature on the pharmaceutical treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage remains daunting. Optimal treatment regimens for patients can be obscured by studies not statistically powered to draw evidenced-based conclusions., Methods: In this chapter, we reviewed the English literature using the National Library of Medicine for studies regarding pharmacotherapies for the treatment of cerebral vasospasm. These studies were then categorized according to the US Preventative Services Task Force ranking system for evidence based medicine and reviewed each pharmacotherapy for its efficacy in the treatment of cerebral vasospasm., Results: Nimodipine (Nimotop), HMG Co-A reductase inhibitor (statins) and enoxaparin (Lovenox) were the only drugs with level-1 evidence available for the treatment of vasospasm from aneurysmal subarachnoid hemorrhage as defined by the US Preventative Services Task Force., Conclusion: As the understanding of the pathophysiological mechanisms of vasospasm after aneurysmal subarachnoid hemorrhage evolves in the basic science laboratory, novel medications are being trialed in humans. However, significantly more work must be carried out in this area before we have an effective medical treatment that can prevent or reverse the devastating events of cerebral vasospasm.

Objective: To evaluate the effects of urinary kallidinogenase on subarachnoid hemorrhage (SAH) in rabbits., Methods: Rabbits symptomatic cerebral vasospasm model was built though Endo method, among the 40 rabbits, 8 died or had severe nervous system syndrome, the other 32 were randomly divided into 4 groups:group A, control group, injection of normal saline to the cisterna magna;group B, subarachnoid hemorrhage;group C, injection of human urinary tissue kallikreins;group D, treated with Nimodipine. The behavior scores, neurological scores and cerebral angiography changes were observed., Results: Food intake obviously decreased and neurological deficit were seen in group B, while which were attenuated in group C and group D, and group A was normal. Comparing the diameter of basilar artery was (1.9 +/- 0.3) mm before SAH, the diameter of group B 4 d later was (1.5 +/- 0.3) mm, 7 d later (1.4 +/- 0.3) mm, the difference was significant (P < 0.05). Comparing with group C on the day 4th and 7th, the diameters of basilar artery were significantly different (P < 0.001). Comparing with group D on the day 4th, 7th and 14th, there was no obvious improvement., Conclusion: Urinary kallidinogenase and Nimodipine can obviously alleviate symptomatic cerebral vasospasm in rabbits remarkably, but the former's effect of attenuating vasospasm is better than that of Nimodipine.

Background: Cognitive changes associated with moderate hypoxia may be related to the elevation of cytosolic calcium (Ca) levels which may, in turn, affect neurotransmitter synthesis and metabolism. We tested whether treatment with nimodipine (NIMO), an L-type Ca channel blocker, would preserve working memory after hypoxic hypoxia., Methods: We randomized 157 Swiss-Webster, 30 to 35 g mice (6 to 8 wk) to 6 groups, which were exposed to the following gas mixtures for 1 hour: (1) O2 21%; (2) O2 21% followed by 0.1 mg/kg of subcutaneous NIMO; (3) O2 21% followed by vehicle (60% polyethylene glycol/40% methanol); (4) O2 10%; (5) O2 10% then NIMO; (6) O2 10% then vehicle. The Object Recognition Test (ORT) was given once either on Day 1 or Day 7 to assess changes in short-term memory. ORT exploits the tendency of mice to prefer novel over familiar objects. Two identical objects were placed in an arena for 15 minutes of training. During the testing 1 hour later, one of the objects was replaced by a new object. Recognition Index (RI) was used to compare performance. It is defined as the time spent exploring the novel object divided by the time spent exploring both objects, the novel plus the familiar, and this ratio is converted to a percentage. RI was analyzed with analysis of variance. Tukey Honestly Significant Difference tests were used for post hoc comparisons when appropriate. P values <0.05 were considered significant., Results: RI for the control group was 68.3% (SE+/-3.6%). RI was 53.7% (SE+/-3.8%) for the 10% O2 group on the first posttreatment day. O2 saturation (SpO2) for the hypoxic group was 71.7% (SE+/-0.5%). By Day 7, RI for the 10% O2 group increased to 64.2% (SE+/-4.7%), which was not significantly different from control. On Day 1, RI was 68.6% (SE+/-5.2%) for hypoxic rodents treated with NIMO. These results were statistically significant. Low RI indicates impaired working memory and high RI indicates intact working memory. These results suggest that NIMO prevented impairment of working memory after moderate hypoxia., Conclusions: NIMO reverses the disturbance of short-term working memory caused by moderate hypoxia in mice. The results may have implications for cognitive changes linked to Ca homeostasis in the postoperative period.

The influence of nimodipine on the cerebral circulation of rats under conditions of global transient cerebral ischemia, myocardial ischemia, and combined disorders of cerebral and coronary circulation was experimentally studied in rats, in comparison to the intact and sham operated animals. It is shown that nimodipine (0.03 mg/kg) enhances circulation in the parietal region of the cerebral cortex to the same extent in both intact rats and those after global transient cerebral ischemia. Under conditions of experimental myocardial infarction, the cerebrovascular effect of nimodipine was significantly decreased in comparison to that in intact and sham operated animals. In contrast to intact and sham operated rats and the rats with myocardial infarction, there were no signs of cerebrovascular activity of nimodipine in animals with combined disorders of coronary and cerebral circulation. A new approach to the search for and investigation of pharmacological agents for the treatment of combined disturbances of cerebral and cardiac circulation is proposed.

Annually about 50,000 patients are hospitalized for acute stroke in Hungary. Of all stroke cases 85% are ischemic, and 15% are hemorrhagic (intracerebral or subarachnoid). In acute ischemic stroke the only registered causal treatment with proven efficacy is thrombolysis with intravenous administration of recombinant tissue plasminogen activator with a 3-hour time window. The indication areas of intraarterial thrombolysis are currently being established for selected cases in selected centers. Other studies examine the options to extend the time window and to test new thrombolytic agents. Despite the large number of studies none of the neuroprotectant agents have been found beneficial in randomized controlled clinical trials in acute stroke. According to the results of studies to date anticoagulant therapy (heparin) cannot be recommended for the routine treatment of acute stroke. Aspirin may be safely administered within 48 hours of ischemic stroke and results in a 1% decrease of death or disability at 6 months after stroke. There were no large studies on the use of other antiplatelet agents in acute stroke. If thrombolysis is performed, antiplatelet or anticoagulant agents should not be administered in the first 24 hours. Further studies are needed to test the efficacy and safety of anticoagulants in special cases of stroke (e.g. crescendo TIA-s, progressing stroke), and to test combined antiplatelet treatment in the acute phase of stroke. In acute intracerebral hemorrhage the beneficial effect of recombinant coagulation factor VII found in a small study could not be proved in a large phase III trial. Currently there is no evidence based pharmacotherapy for the specific treatment of intracerebral hemorrhage. In subarachnoid hemorrhage nimodipine was found effective in preventing vasospasm and thus secondary ischemic cerebral damage. Although the results of individual trials are conflicting, a systematic review on the effects of statins suggests a similar effect. Due to the limited options of evidence based treatments of acute stroke primary prevention has utmost importance.

Objective: To observe the effect of a integrative medical regimen (IMR), i.e. combined use of Jiangya Capsule (JYC) and Nimodipine (ND), on blood pressure, TCM clinical symptoms, and blood levels of vascular endothelial function and hypersensitive C-reactive protein (hs-CRP) in elderly patients with isolated systolic hypertension (EISH)., Methods: Adopting randomized, double-blinded and controlled principle, a trial was conducted on 135 patients with EISH by randomized them into three groups, they were administered IMR (Group A), JYC plus ND simulator (Group B) and ND plus JYC simulator (Group C) respectively, for 4 weeks. Changes of blood pressure and TCM symptoms, as well as the levels of serum nitric oxide (NO), plasma endothelin-1 (ET-1), 6-keto-prostaglandin 1alpha (6-keto-PGF(1alpha)), thromboxane B2 (TXB2) and hs-CRP were observed before and after treatment., Results: After treatment the systolic blood pressure reduced and clinical symptoms improved, with serum NO and 6-keto-PGF(1alpha) lelels elevated, plasma ET-1, TXB2 and serum hs-CRP decreased in all the three groups (P<0.05 or P<0.01). But the inter-group comparisons showed that the effect in Group A was superior to the other two groups in decreasing systolic pressure, and superior to Group C in improving clinical symptoms, elevating serum NO and decreasing plasma TXB2 (P <0.05)., Conclusion: The integrative medical regimen of combined use JYC and ND has markedly effect in lowering blood pressure, it could obviously improve the symptoms and vascular endothelial function, and inhibit the level of inflammatory factor in patients with EISH.

Objective: To assess the therapeutic effect of auricular point taping and pressing therapy on vascular dementia (VD)., Methods: One hundred and eighty cases of vascular dementia were randomly divided into an auricular point taping and pressing group and a western medicine group, 90 cases in each group. The auricular point taping and pressing group was treated by auricular point taping and pressing at auricular points Shennen, Nao (brain), Shen (kidney), Zhen (pulvinal), and the western medicine group by oral administration of Nimodipine, thrice each day, 30 mg each time. They were treated for 12 weeks. The scores of mini-mental state examination (MMSE) and activities of daily living (ADL), and adverse reaction were observed., Results: The scores of MMSE before treatment and 12 weeks after treatment were 18.00 +/- 3.88 and 20.83 +/- 3.74 in the auricular point taping and pressing group, and 17.80 +/- 3.82 and 20.70 +/- 3.53 in the western medicine group, respectively, with significant increases in scores of MMSE after treatment in the two groups (both P < 0.01) and with no significant difference between the two groups (P > 0.05). The scores of ADL before treatment and 12 weeks after treatment were 44.90 +/- 14.84 and 39.60 +/- 12.45 in the auricular point taping and pressing group, and 45.70 +/- 14.86 and 39.10 +/- 13.44 in the western medicine group, respectively, with significant decreases after treatment in the two groups (both P < 0.01) and with no significant difference between the two groups (P > 0.05). In the auricular point taping and pressing group, 2 cases withdrew from the test because adhesive plaster allergic reaction induced severe itch of the auricle. In the western medicine group, one case had mild dizziness and another case had diarrhea respectively., Conclusion: Auricular point taping and pressing and Nimodipine have similar therapeutic effect on vascular dementia, and have no obvious adverse reaction, except adhesive plaster allergic reaction.

In the present study, the effect of nimodipine was investigated in a patient with severe head trauma. Nimodipine was administered into the peripheral vein to prevent secondary neuronal damages in patients. The five patients in control group were treated according to the standard procedures without nimodipine. Other five patients in nimodipine group were treated with standard procedures plus nimodipine. Cerebral perfusion pressure (CPP), intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), jugular lactate and glucose levels were measured. Additionally, all patients were evaluated with Glascow outcome score (GOS) before discharge. It was found that CPP (p<0.05) and SjvO2 (p<0.05) were significantly higher; but, ICP (p<0.001), jugular lactate (p<0.05) and jugular glucose (p<0.05) were lower in nimodipine than that of control groups. Again, GOS values were significantly higher in nimodipine than that of control groups (p<0.05). Results of this study revealed that nimodipine can improve cerebral metabolism and outcome in patient with severe head trauma. Thus, nimodipine may be considered as a protective agent against severe head trauma related neuronal injuries.

Ethnopharmacological Relevance: Total saponins of Panax notoginseng (TSPN), main constituents extracted from Panax Notoginseng, a highly valued traditional Chinese medicine, have been shown to be an effective agent on cerebral infarction., Aim of the Study: The effects of TSPN on apoptosis and expressions of caspase-1, caspase-3 and caspase-8 were studied after cerebral ischemia for 2 h followed by reperfusion for 46 h in rats., Materials and Methods: Rats were subjected to transient middle cerebral artery occlusion (MCAO) model using the intraluminal thread. TSPN was administered intraperitoneally at 5 min before and 12 h, 24 h and 36 h after MCAO, respectively., Results: TSPN (at the dose of 25 mg/kg) significantly attenuated TUNEL-positive cells and reduced the expression of caspase-1 and caspase-3 compared to the model group, while it had no obvious effect on the expression of caspase-8., Conclusions: The neuroprotective effect of TSPN on focal ischemia may be related to inhibition of apoptosis and caspases activation.

Object: The calcium antagonist nimodipine has been shown to reduce the incidence of ischemic complications following aneurysmal subarachnoid hemorrhage (SAH). Although most randomized studies have been focused on the effect of the peroral administration of nimodipine, intravenous infusion is an alternative and the preferred mode of treatment in many centers. It is unknown whether the route of administration is of any importance for the clinical efficacy of the drug., Methods: One hundred six patients with acute aneurysmal SAH were randomized to receive either peroral or intravenous nimodipine treatment. The patients were monitored for at least 10 days after bleeding in terms of delayed ischemic neurological deficits (DINDs) and with daily measurements of blood flow velocities in the middle cerebral arteries by using transcranial Doppler ultrasonography. Three months after SAH, clinical outcome and new cerebral infarctions according to MR imaging studies were recorded., Results: Baseline characteristics (age, sex distribution, clinical status on admission, radiological findings, and aneurysm treatment) did not differ between the treatment groups. There was no significant difference in the incidence of DINDs (28 vs 30% in the peroral and intravenous groups, respectively) or middle cerebral artery blood flow velocities (> 120 cm/second, 50 vs 45%, respectively). Clinical outcome according to the Glasgow Outcome Scale was the same in both groups, and there was no difference in the number of patients with new infarctions on MR imaging., Conclusions: The results suggest that there is no clinically relevant difference in efficacy between peroral and intravenous administration of nimodipine in preventing DINDs or cerebral vasospasm following SAH.