Calcium antagonists are widely used in the clinical treatment of ischemic cerebrovascular disease because of their vascular and neuroprotective effects. Nimodipine, a typical calcium antagonist, can cross the blood-brain barrier and act selectively at neurons and blood vessels of target tissues, thus exerting neuroprotective effects. The aim of the present study was to explore the hot spots and future trends of research on the neuroprotective effects of nimodipine. We retrieved 425 articles on the neuroprotective effects of nimodipine that were indexed in the Web of the Science database between 2000 and 2014. The retrieved articles were analyzed using document analysis reporting and the derived information function in the Web of Science, and the information visualization software CiteSpace III. The reference co-citation network was plotted, and the high frequency key words in these publications were used to analyze the research fronts and development trends for nimodipine neuroprotection. According to these co-citation clusters, the research front of nimodipine neuroprotection is the use of randomized controlled trials to study nimodipine intervention of subarachnoid hemorrhage. Using time zone view analysis on hot spots labeled with a key word, the areas of interest in the field of nimodipine neuroprotection are nimodipine pharmacology and therapeutics, blood-brain barrier, trials, and anti-angiospasm.

Background: A neuroprotective effect of nimodipine on acute cerebral infarction has been confirmed, but there are few reports regarding the therapeutic effect of nimodipine on acute massive cerebral infarction. There is also no consensus on the optimal time window for the use and dosage of nimodipine. This trial is planned to answer these questions using a double-blind randomized controlled design. Methods/Design: This is a double-blind randomized controlled trial. The experiments will be conducted in the Department of Neurology, Central Hospital Affiliated to Shenyang Medical College of China. One hundred patients with acute massive cerebral infarction will be randomly assigned to a control group and a treatment group. Patients in the control and treatment groups will receive intravenous infusion of citicoline and intravenous infusion of nimodipine (10 mg/d) respectively, for 7 consecutive days. Simultaneously, to determine the appropriate time window for treatment with nimodipine, patients in the treatment group will be divided into four subgroups according to the time of nimodipine administration: < 3 hours, 3-6 hours, 6-24 hours, and > 24 hours. The main outcome measures are: the National Institutes of Health Stroke Scale and the Rankin scale will be used to assess the severity and recovery of neurological impairment, respectively. Cranial computed tomography and magnetic resonance imaging will be used to evaluate brain lesions and the Barthel index will be used to assess the activities of daily living. Secondary outcome measures are heart rate and blood pressure. Discussion: It is hoped that the experimental results can determine the best application time window and dosage of nimodipine for acute massive cerebral infarction. Trial registration: ClinicalTrials.gov identifier: NCT02248233; registered on 22 September 2014.