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Tao Hong, Yang Wang, Hai-tao Wang, and Huan Wang

Object

The gap junction is important in the propagation of dilation/constriction signals along vessels for coordinated behavior in control of vascular tone. The authors hypothesized that gap junctions might play a role in cerebral vasospasm following subarachnoid hemorrhage (SAH). The aims of the present study were to investigate the role of gap junctions and to observe the potential therapeutic efficacy of gap junction blockers in cerebral vasospasm in vitro and in vivo.

Methods

For the in vitro investigation, the effect of heptanol on the oxyhemoglobin (HbO2)-induced contraction of isolated rabbit basilar arteries (BAs) was observed by using an isometric tension-recording method. For the in vivo experiments, the potential therapeutic efficacy of heptanol and carbenoxolone was surveyed after it was given intravenously in the rabbit double-hemorrhage model. Light microscopy was performed to assess the morphological changes in the arteries examined.

Results

For the in vitro method, heptanol significantly inhibited the sustained contraction induced both by HbO2 and K+ in the BA rings. The magnitude of the heptanol-induced relaxation was dose dependent. The inhibitory effect of heptanol on the K+-induced vasoconstriction was weaker than that on the HbO2-induced constriction. After arterial rings were pretreated for 10 minutes, heptanol significantly decreased their responses to the HbO2-induced contraction. For the in vivo method, heptanol and carbenoxolone significantly decreased the narrowing of BAs when given intravenously in the rabbit double-hemorrhage model. In both treated groups, the diameters of the arteries had not changed significantly on Day 7 compared with those of the arteries in the SAH + vehicle and the SAH-only group.

Conclusions

Heptanol and carbenoxolone significantly inhibited the experimental cerebral vasospasm both in vitro and in vivo. Blockage of gap junctions is a probable candidate for a new approach in the treatment of cerebral vasospasm. Gap junctions may play a pathophysiological role in cerebral vasospasm.

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Tao Yang, Liang Wu, Jingyi Fang, Chenlong Yang, Xiaofeng Deng, and Yulun Xu

OBJECT

Intramedullary neurenteric cysts (NECs) are exceedingly rare lesions and have been previously reported in case reports. The aim of this study was to determine the clinical manifestations, radiological features, and long-term prognosis of patients with such lesions.

METHODS

The authors retrospectively reviewed the records of 13 patients with an intramedullary NEC. Each patient underwent MRI, laminotomy, and microsurgery. The accurate diagnosis was based on imaging and pathology findings. Each patient's follow-up status was determined through individual office visits and a structured telephone interview.

RESULTS

The series included 7 male and 6 female patients. Progressive or intermittent motor deficit was the main symptom associated with or without pain or sensory disturbance. Five cysts were located in the cervical cord, 1 in the cervicothoracic cord, 3 in the thoracic cord, and 4 in the conus medullaris. Concurrent malformations included scoliosis (3 cases), fusion of rib (1 case), enlarged spinal canal (1 case), tethered spinal cord (1 case), and ectocardia (1 case). Gross-total resection of the cyst was achieved in 8 cases, and subtotal resection (STR) was achieved in 5 cases. All patients were followed up, with a mean duration of 66.5 months. Cyst recurrence was observed in 4 cases after STR. In 2 cases the patients underwent reoperation; the other 2 patients remained clinically stable and did not undergo reoperation. At the last evaluation, neurological function was improved in 11 patients and remained stable in 2 patients.

CONCLUSIONS

Intramedullary NECs should be considered in the differential diagnosis of a middle-aged patient with intermittent neurological symptoms and concurrent malformations. Early surgery is advocated to prevent permanent neurological deficits. When gross-total resection cannot be achieved, maximally safe removal under the protection of intraoperative neuromonitoring is advised. Because of the high risk of cyst recurrence, routine follow-up MRI is needed. If a residual cyst shows obvious regrowth and results in neurological deficits, timely reoperation with a goal of STR should be performed.

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Yi Yang, Qiu Li, Marian T. Nakada, Tao Yang, and Ashfaq Shuaib

Object. Antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) receptor complex are currently used for the treatment of acute coronary syndromes. The platelet GPIIb/IIIa mediates platelet aggregation, and blocking this receptor complex can reduce or prevent arterial thrombosis. To study the recanalization efficacy of a GPIIb/IIIa antagonist in treating cerebral ischemia, we investigated the therapeutic effects of murine 7E3 F(ab′)2 in a focal embolic cerebral ischemia model in rats.

Methods. Focal cerebral ischemia was produced by introducing an autologous thrombus into the right side of the middle cerebral artery (MCA). Thirty male Wistar rats were randomly divided into three groups of 10 rats each: control, 7E3 F(ab′)2 administered 1 hour postischemia, and 7E3 F(ab′)2 administered 3 hours postischemia. Animals in the therapeutic groups received intravenous infusion of 6 mg/kg 7E3 F(ab′)2 at 1 or 3 hours following cerebral embolization. Brain infarct volume, neurobehavioral scores, duration of bleeding, and findings on angiograms of the MCA (before and after infusion) were assessed in all animals.

Angiographic evaluation revealed full MCA recanalization in three of 10 animals in each 7E3 F(ab′)2 treatment group. Animals in these groups exhibited a significant reduction in infarct volume when compared with animals in the control group: 1) infarct volume 1 hour postischemia, 22 ± 13.9% (p = 0.005); 2) infarct volume 3 hours postischemia, 22.1 ± 14.8% (p = 0.008); and 3) infarct volume in control animals, 42.4 ± 16%. Postischemia treatment with 7E3 F(ab′)2 also improved the animal's neurobehavioral performance. The duration of bleeding significantly increased by more than two times, but there was no associated increase in intracerebral hemorrhage in any group.

Conclusions. On the basis of their findings, the authors conclude that murine 7E3 F(ab′)2 is a potent and safe antiplatelet agent in this experimental focal embolic cerebral ischemia model. Neuronal lesions were significantly reduced when the treatment was delayed up to 3 hours.

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Tao Yang and Qin-Shui Yin

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Feng Xu, Hai Jin, Xingwang Yang, Xiao Sun, Yu Wang, Mengting Xu, and Yingqun Tao

OBJECTIVE

The aim of this study was to determine whether a modified registration method could reduce registration error and postoperative electrode vector error and to analyze the method’s clinical significance in deep brain stimulation (DBS) surgery.

METHODS

The first part of the study involved a skull model, in which three registration methods were tested using the ROSA (robotic stereotactic assistance) system. In the second part, four registration methods were clinically tested in patients undergoing DBS surgery using the ROSA system. Thirty-three patients (65 sides, group I) underwent the conventional registration method 2E, and registration errors were recorded. Thirty-eight patients (75 sides, group II) underwent four types of modified registration methods including 2A, 2B, 2C, and 2D. Registration and electrode vector errors, intraoperative electrophysiological signal length (IESL), and DBS power-on voltage were recorded. The primary measure of efficacy was the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) and UPDRS Part III scores from baseline to 10 weeks after surgery.

RESULTS

In the skull model, the registration error (mean ± SD) was 0.56 ± 0.11 mm for method 1A, 0.35 ± 0.11 mm for method 1B (vs. 1A, p < 0.001), and 0.90 ± 0.15 mm for method 1C (vs. 1A, p < 0.001). In the clinical study, method 2C was selected for DBS surgery in group II since it had the smallest registration error among the four methods tested. The registration error was 0.62 ± 0.22 mm (mean ± SD) for group I and 0.27 ± 0.07 mm for group II (p < 0.001). Postoperative electrode vector error was 0.97 ± 0.31 mm for group I and 0.65 ± 0.23 mm for group II (p < 0.001). There was a positive correlation between registration error and electrode vector error in both groups (group I: r = 0.69, p < 0.001; group II: r = 0.71, p < 0.001). The mean IESL was 5.0 ± 0.9 mm in group I and 5.8 ± 0.7 mm in group II (p < 0.001). The mean DBS power-on voltage was 1.63 ± 0.44 V in group I and 1.48 ± 0.38 V in group II (p = 0.027). In the UPDRS score, group I showed 50% ± 16% improvement and group II showed 52% ± 18% improvement (p = 0.724); there was no statistically significant difference in improvement on the UPDRS.

CONCLUSIONS

In DBS surgery assisted by the ROSA system, registration error and electrode vector error showed a positive correlation. The modified registration method could reduce the registration error and electrode vector error, but the long-term effects need to be further observed and evaluated.

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Wen-Chao Liu, Liang Wen, Tao Xie, Hao Wang, Jiang-Biao Gong, and Xiao-Feng Yang

OBJECTIVE

Erythropoietin (EPO) exerts a neuroprotective effect in animal models of traumatic brain injury (TBI). However, its effectiveness in human patients with TBI is unclear. In this study, the authors conducted the first meta-analysis to assess the effectiveness and safety of EPO in patients with TBI.

METHODS

In December 2015, a systematic search was performed of PubMed, Web of Science, MEDLINE, Embase, the Cochrane Library databases, and Google Scholar. Only English-language publications of randomized controlled trials (RCTs) using EPO in patients with TBI were selected for analysis. The assessed outcomes included mortality, favorable neurological outcome, hospital stay, and associated adverse effects. Continuous variables were presented as mean difference (MD) with a 95% confidence interval (CI). Dichotomous variables were presented as risk ratio (RR) or risk difference (RD) with a 95% CI. Statistical heterogeneity was examined using both I2 and chi-square tests.

RESULTS

Of the 346 studies identified in the search, 5 RCTs involving 915 patients met the inclusion criteria. The overall results demonstrated that EPO significantly reduced mortality (RR 0.69, 95% CI 0.49–0.96, p = 0.03) and shortened the hospitalization time (MD −7.59, 95% CI −9.71 to −5.46, p < 0.0001) for patients with TBI. Pooled results of favorable outcome (RR 1.00, 95% CI 0.88–1.15, p = 0.97) and deep vein thrombosis (DVT; RD 0.00, 95% CI −0.05 to 0.05, p = 1.00) did not show a significant difference.

CONCLUSIONS

The authors suggested that EPO is beneficial for patients with TBI in terms of reducing mortality and shortening hospitalization time without increasing the risk of DVT. However, its effect on improving favorable neurological outcomes did not reach statistical significance. Therefore, more well-designed RCTs are necessary to ascertain the optimum dosage and time window of EPO treatment for patients with TBI.

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Tao-Chen Lee, Kang Lu, Lin-Cheng Yang, Hsuan-Ying Huang, and Cheng-Loong Liang

Object. Because modern imaging techniques now allow for early diagnosis of spinal tuberculosis, more conservative management options are possible. The authors evaluated the effectiveness of transpedicular instrumentation for treatment of thoracolumbar and lumbar spinal tuberculosis in patients with mild bone destruction and the main symptom of “instability catch” (a sudden painful “snap” that occurs when one extends from a forward bent to an upright position).

Methods. Eighteen patients (nine men and nine women, age range 49–71 years) with spinal tuberculosis were treated with transpedicular instrumentation that was supplemented with posterolateral fusion and chemotherapy. All patients were wheelchair dependent or bed-ridden due to severe instability catch, with a mean symptom duration of 2.5 months (range 1–6 months). Two contiguous vertebrae were involved in 17 patients, and a single vertebrae was involved in one. In five patients mild neurological deficits (Frankel Grade D) were present. During surgery, the screws were implanted into the two nonaffected pedicles nearest the lesion to stabilize the involved segments. No attempt at radical debridement or neural decompression was undertaken. The follow-up period ranged from 21 to 40 months. Postoperatively the instability catch was relieved within 10 days (excellent outcome) and within 1 month (good outcome) in seven and eight patients, respectively, and within 3 months (fair outcome) in two; in the remaining patient, the symptom did not resolve (poor outcome). A short duration of symptoms (generally < 3 months) and bone destruction of less than 50% in the involved vertebral bodies were observed in patients who made a good or excellent outcome. During the follow-up period, good maintenance of spinal alignment, stabilization of the involved segment, and resolution of the inflammatory process were shown; however, there was no strong evidence that fusion had occurred at the bony defect. Patients in whom a fair outcome was achieved experienced a longer duration of symptoms, and in each, one vertebral body with greater than 50% bone destruction was demonstrated. However, good maintenance of spinal alignment was also shown during the follow-up period. The patient whose outcome was poor had the longest history (6 months) of symptoms and the most extensive involvement of the spine (> 50% destruction of two adjacent lumbar vertebral bodies). Postoperatively, implant failure occurred and the patient developed a wound infection.

Conclusions. Transpedicular instrumentation provides rapid relief of instability catch and prevents late angular deformity in patients with thoracolumbar and lumbar spinal tuberculosis in whom limited (< 50%) bone destruction of the involved vertebral bodies has been shown and whose main symptom is instability catch.

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Chen Xu Wang, Tao Yang, Raza Noor, and Ashfaq Shuaib

Object

Pyridoxal-5-phosphate (PLP), the biologically active form of pyridoxine, can rescue neurons from death in vitro and in vivo. In the present project, the authors have studied whether MC-1, an analog of PLP, alone or in combination with the thrombolytic agent tissue plasminogen activator (tPA), can protect the brains of rats injured by ischemia.

Methods

Ischemic brain injury was induced in rats by injecting a preformed blood clot in the middle cerebral artery (MCA). Neurological deficits and infarct volumes caused by the embolus were measured to evaluate the effects of MC-1 on the ischemic injury. Systemic blood pressure and local brain blood flow were also monitored.

Administration of different doses of MC-1 1 hour after embolization significantly reduced the infarct volume and improved functional recovery. Injection of MC-1 (40 mg/kg) at 3 or 6 hours after embolization also reduced the volume of the infarct significantly and improved functional recovery. Combined treatment with MC-1 and tPA was also neuroprotective, although it was not superior to treatment involving either MC-1 or tPA alone. Treatment with MC-1 did not result in significant changes in either systemic blood pressure or local blood flow in the ischemic brain.

Conclusions

These data support the hypothesis that in the focal embolic stroke model in rats MC-1 is a neuroprotective agent. The neuroprotection this compound provides still exists when MC-1 administration is delayed up to 6 hours after ischemic injury.

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Ruth Prieto and Jose María Pascual

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Xiang-Ming Li, Jian-Tao Yang, Yi Hou, Yi Yang, Ben-Gang Qin, Guo Fu, and Li-Qiang Gu

OBJECT

Donor-side morbidity associated with contralateral C-7 (CC7) nerve transfer remains controversial. The purpose of this study was to evaluate functional deficits in the donor limb resulting from prespinal route CC7 nerve transfer.

METHODS

A total of 63 patients were included. Forty-one patients had undergone CC7 nerve transfer surgery at least 6 months previously and were assigned to one of 2 groups based on the duration of postoperative follow-up. Group 1 (n = 21) consisted of patients who had undergone surgery between 6 months and 2 years previously, and Group 2 (n = 20) consisted of patients who had undergone surgery more than 2 years previously. An additional 22 patients who underwent CC7 nerve transfer surgery later than those in Groups 1 and 2 were included as a control group (Group 3). Results of preoperative testing in these patients and postoperative testing in Groups 1 and 2 were compared. Testing included subjective assessments and objective examinations. An additional 3 patients had undergone surgery more than 6 months previously but had severe motor weakness and were therefore evaluated separately; these 3 patients were not included in any of the study groups.

RESULTS

The revised Short-Form McGill Pain Questionnaire (SF-MPQ-2) was the only subjective test that showed a significant difference between Group 3 and the other 2 groups, while no significant differences were found in objective sensory, motor, or dexterity outcomes. The interval from injury to surgery for patients with a normal SF-MPQ-2 score in Groups 1 and 2 was significantly less than for those with abnormal SF-MFQ-2 scores (2.4 ± 1.1 months vs 4.6 ± 2.9 months, p = 0.002). The 3 patients with obvious motor weakness showed a tendency to gradually recover.

CONCLUSIONS

Although some patients suffered from long-term sensory disturbances, resection of the C-7 nerve had little effect on the function of the donor limb. Shortening preoperative delay time can improve sensory recovery of the donor limb.