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Sha Zhao, Zhen Liu, Zihan Yu, Xinran Wu, Rui Li, and Xiaobo Tang

OBJECTIVE

Inflammation plays a key role in secondary brain damage following intracerebral hemorrhage (ICH). Glycogen synthase kinase–3β (GSK-3β) plays a strong proinflammatory role in many CNS diseases, including stroke. The present study was undertaken to examine the effects of 6-bromoindirubin-3ʹ-oxime (BIO), a specific inhibitor of GSK-3β, on inflammation in ICH rats.

METHODS

An ICH rat model was induced by autologous whole-blood injection into the striatum. First, 10, 20, 40, 60, 80, or 100 μg/kg BIO was applied to ICH animals to determine an optimal dosage for producing sufficient GSK-3β inhibition in rat ipsilateral hippocampus by Western blotting. Second, 40 μg/kg BIO was applied to ICH rats for 1, 3, 7, or 14 days, respectively, to determine a suitable intervention time course of BIO by Western blotting analysis on GSK-3β. Third, Western blotting and enzyme-linked immunosorbent assay were used for quantification of inflammation-related factors upstream or downstream of GSK-3β in rat ipsilateral hippocampus. Then, immunohistochemical staining was applied to detect activated microglia and apoptotic cells in rat ipsilateral hippocampus. Last, neurobehavioral tests were performed to assess the sensorimotor impairments in the ICH rats.

RESULTS

The results show that BIO 1) blocked GSK-3βTyr216 phosphorylation/activation, thus stabilizing β-catenin, increasing upstream brain-derived neurotrophic factor and downstream heat shock protein 70 levels, and decreasing the levels of nuclear factor–κB p65 and cyclooxygenase 2; 2) decreased the levels of the proinflammatory cytokines tumor necrosis factor–α and interleukin (IL)–1β and IL-6 and elevated the level of antiinflammatory cytokine IL-10; 3) inhibited microglia activation and cell apoptosis; and 4) improved the sensorimotor deficits of ICH rats.

CONCLUSIONS

BIO posttreatment inhibited microglia activation, prevented inflammation and hippocampal cell death, and ameliorated functional and morphological outcomes in a rat ICH model through inactivation of GSK-3β.

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Jun Jiang, Zezhang Zhu, Bangping Qian, Zhen Liu, and Yong Qiu

Cervical myelomeningocele (MMC) is an uncommon congenital malformation of the spinal cord and accounts for a small proportion of neural tube defects. These lesions mostly occur in the dorsal part of the body. Only a single case of an anterior cervical MMC has been previously reported. The authors report a second case of anterior cervical MMC diagnosed when the patient began to experience symptoms of bilateral hand weakness in adulthood. In this patient, MR imaging of the cervical spine showed an anterior cervical MMC at the C6–7 level with hydrocephalus, thinning of the genu and trunk of the corpus callosum, maldevelopment of the cerebellar tonsils, and expansion of the fourth ventricle, posterior cranial fossa, and subarachnoid space. A CT scan and a 3D CT reconstruction of the cervical spine clearly demonstrated contiguous fusions of multiple lower-cervical vertebrae and neural arches, which was consistent with Type III Klippel-Feil syndrome. The patient was advised to undergo operative treatment to prevent the progression of her neurological deficit. However, after being notified of the potential neurological risks, the patient declined surgery and opted for conservative treatment with a hard neck collar. At 4 months' follow-up, the patient's neurological deficit remains stable with the MMC left untreated. The authors presume that the possible pathogenesis of anterior cervical MMC may greatly differ from that of posterior lesions. This lesion could also be associated with multiple other spinal abnormalities, which highlights the importance of comprehensive preoperative radiological examinations.

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Weiguo Zhu, Zhen Liu, Shifu Sha, Jing Guo, Hongda Bao, Leilei Xu, Yong Qiu, and Zezhang Zhu

OBJECTIVE

Previous studies have reported spinal straightening and pelvic retroversion when changing from erect to sitting posture in patients with adolescent idiopathic scoliosis (AIS), which were thought to be related to low-back pain after sitting for long periods. However, the sitting sagittal alignment after posterior spinal fusion has not been evaluated. This study aims to assess the influence of posterior fusion surgery upon sitting sagittal spinopelvic alignment in adolescents with idiopathic thoracic curves (thoracic AIS [T-AIS]).

METHODS

A total of 44 T-AIS patients (30 Lenke I and 14 Lenke II) from the authors’ center were included in this study. Preoperative and postoperative long-cassette lateral radiographs of the spine and pelvis were obtained with the patients in standing and sitting positions. Thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), and pelvic tilt (PT) were measured on standing and sitting lateral radiographs. Patients were divided into selective thoracic fusion (STF) and nonselective thoracic fusion (NSTF) groups.

RESULTS

At baseline, TK, LL, and SS decreased by 27.5%, 42.1%, and 31.1%, respectively, from the standing to the sitting position, while PT increased by 193.6%. After posterior spinal fusion, increased TK, LL, and SS and corresponding decreased PT were observed compared to baseline parameters in the sitting position. Comparison of postoperative sitting and standing values for the whole cohort showed that the mean LS and SS values were significantly lower in the sitting position (decreased by 14.0% and 13.9%, respectively, compared to standing), whereas the mean PT value was significantly greater (increased by 39.0%, compared to standing). Similar changes were also observed in the STF group: postoperatively the mean LL value was 15.6% lower in sitting than in standing, while the mean SS value was 11.5% lower. However, no obvious changes of the postoperative values in sitting were found in the NSTF group.

CONCLUSIONS

Nonselective thoracic fusion surgery in T-AIS patients diminished spinal straightening and pelvic retroversion during sitting. Reducing distal fusion levels was of special value in not only saving more lumbar mobility, but also preserving the function of pelvic posterior rotation.

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Yang Li, Xinxin Yuan, Shifu Sha, Zhen Liu, Weiguo Zhu, Yong Qiu, Bin Wang, Yang Yu, and Zezhang Zhu

OBJECTIVE

The aim of this study was to investigate how implant density affects radiographic results and clinical outcomes in patients with dystrophic scoliosis secondary to neurofibromatosis Type 1 (NF1).

METHODS

A total of 41 patients with dystrophic scoliosis secondary to NF1 who underwent 1-stage posterior correction between June 2011 and December 2013 were included. General information about patients was recorded, as were preoperative and postoperative scores from Scoliosis Research Society (SRS)–22 questionnaires. Pearson correlation analysis was used to analyze the associations among implant density, coronal Cobb angle correction rate and correction loss at last follow-up, change of sagittal curve, and apical vertebral translation. Patients were then divided into 2 groups: those with low-density and those with high-density implants. Independent-sample t-tests were used to compare demographic data, radiographic findings, and clinical outcomes before surgery and at last follow-up between the groups.

RESULTS

Significant correlations were found between the implant density and the coronal correction rate of the main curve (r = 0.505, p < 0.01) and the coronal correction loss at final follow-up (r = −0.379, p = 0.015). There was no significant correlation between implant density and change of sagittal profile (p = 0.662) or apical vertebral translation (p = 0.062). The SRS-22 scores improved in the appearance, activity, and mental health domains within both groups, but there was no difference between the groups in any of the SRS-22 domains at final follow-up (p > 0.05 for all).

CONCLUSIONS

Although no significant differences between the high- and low-density groups were found in any of the SRS-22 domains at final follow-up, higher implant density was correlated with superior coronal correction and less postoperative correction loss in patients with dystrophic NF1-associated scoliosis.

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Weiguo Zhu, Weixiang Sun, Leilei Xu, Xu Sun, Zhen Liu, Yong Qiu, and Zezhang Zhu

OBJECTIVE

Recently, minimally invasive scoliosis surgery (MISS) was introduced for the correction of adult scoliosis. Multiple benefits including a good deformity correction rate and fewer complications have been demonstrated. However, few studies have reported on the use of MISS for the management of adolescent idiopathic scoliosis (AIS). The purpose of this study was to investigate the outcome of posterior MISS assisted by O-arm navigation for the correction of Lenke Type 5C AIS.

METHODS

The authors searched a database for all patients with AIS who had been treated with either MISS or PSF between November 2012 and January 2014. Levels of fusion, density of implants, operation time, and estimated blood loss (EBL) were recorded. Coronal and sagittal parameters were evaluated before surgery, immediately after surgery, and at the last follow-up. The accuracy of pedicle screw placement was assessed according to postoperative axial CT images in both groups. The 22-item Scoliosis Research Society questionnaire (SRS-22) results and complications were collected during follow-up.

RESULTS

The authors retrospectively reviewed the records of 45 patients with Lenke Type 5C AIS, 15 who underwent posterior MISS under O-arm navigation and 30 who underwent posterior spinal fusion (PSF). The 2 treatment groups were matched in terms of baseline characteristics. Comparison of radiographic parameters revealed no obvious difference between the 2 groups immediately after surgery or at the final follow-up; however, the MISS patients had significantly less EBL (p < 0.001) and longer operation times (p = 0.002). The evaluation of pain and self-image using the SRS-22 showed significantly higher scores in the MISS group (p = 0.013 and 0.046, respectively) than in the PSF group. Postoperative CT showed high accuracy in pedicle placement in both groups. No deep wound infection, pseudarthrosis, additional surgery, implant failure, or neurological complications were recorded in either group.

CONCLUSIONS

Minimally invasive scoliosis surgery is an effective and safe alternative to open surgery for patients with Lenke Type 5C AIS. Compared with results of the open approach, the outcomes of MISS are promising, with reduced morbidity. Before the routine use of MISS, however, long-term data are needed.

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Jian Zheng, Zhen Liu, Weishan Li, Jiaxin Tang, Dongwei Zhang, and Xiaobo Tang

OBJECTIVE

Inflammation and apoptosis are two key factors contributing to secondary brain injury after intracerebral hemorrhage (ICH). The objective of this study was to evaluate the effects of lithium posttreatment on behavior, brain atrophy, inflammation, and perihematomal cell death. Furthermore, the authors aimed to determine the role of the pro-apoptotic glycogen synthase kinase-3β (GSK-3β) after experimental ICH.

METHODS

Male Sprague-Dawley rats (n = 108) were subjected to intracerebral infusion of semicoagulated autologous blood. Window of opportunity and dose optimization studies of lithium on ICH-induced injury were performed by measuring neurological deficits. Animals with ICH received vehicle administration or lithium posttreatment (60 mg/kg) for up to 21 days. Hemispheric atrophy was evaluated. Perihematomal cell death was quantified through terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The number of myeloperoxidase (MPO)-positive neutrophils and OX42-positive microglia in the perihematomal areas were calculated. Western blotting was used for the quantification of GSK-3β, heat shock protein 70 (HSP70), nuclear factor-κB p65 (NF-κB p65), and cy-clooxygenase-2 (COX-2).

RESULTS

Lithium, at a dose of 60 mg/kg initiated from 2 hours after injury, exhibited the best effects of improving neurological outcomes 3, 5, 7, 14, 21, and 28 days after ICH, reduced the hemispheric atrophy at 42 days after surgery, and reduced the number of TUNEL-positive cells, MPO-positive neutrophils, and OX42-positive microglia in the perihematomal areas. Furthermore, lithium posttreatment modulated GSK-3β, increased HSP70, and decreased NF-κB p65 and COX-2 expression in the ipsilateral hemisphere.

CONCLUSIONS

Lithium posttreatment at a dose of 60 mg/kg, initiated beginning 2 hours after injury, improves functional and morphological outcomes, and inhibits inflammation and perihematomal cell death in a rat model of semicoagulated autologous blood ICH through inactivation of GSK-3β.

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Song Li, Saihu Mao, Changzhi Du, Zezhang Zhu, Benlong Shi, Zhen Liu, Jun Qiao, and Yong Qiu

OBJECTIVE

Dystrophic lumbar scoliosis secondary to neurofibromatosis type 1 (DLS-NF1) may present an atypical, unique curve pattern associated with a high incidence of coronal imbalance and regional kyphosis. Early surgical intervention is complicated and risky but necessary. The present study aimed to assess the unique characteristics associated with the surgical treatment of DLS-NF1.

METHODS

Thirty-nine consecutive patients with DLS-NF1 treated surgically at a mean age of 14.4 ± 3.9 years were retrospectively reviewed. Patients were stratified into three types according to the coronal balance classification: type A (C7 translation < 30 mm), 22 patients; type B (concave C7 translation ≥ 30 mm), 0 patients; and type C (convex C7 translation ≥ 30 mm), 17 patients. Types B and C were considered to be coronal imbalance. The diversity of surgical strategies, the outcomes, and the related complications were analyzed.

RESULTS

The posterior-only approach accounted for 79.5% in total; the remaining 20.5% of patients received either additional anterior supplemental bone grafting (12.8%) to strengthen the fixation or convex growth arrest (7.7%) to reduce growth asymmetry. The lower instrumented vertebra (LIV) being L5 accounted for the largest share (41%), followed by L4 and above (35.9%), the sacrum (15.4%), and the pelvis (7.7%). Type C coronal imbalance was found in 23 patients (59%) postoperatively, and the incidence was significantly higher in the preoperative type C group (14/17 type C vs 9/22 type A, p = 0.020). All the patients with postoperative coronal imbalance showed ameliorative transition to type A at the last visit. The rate of screw malposition was 30.5%, including 9.9% breached medially and 20.6% breached laterally, although no serious neurological impairment occurred. The incidence of rod breakage was 16.1% (5/31) and 0% in patients with the posterior-only and combined approaches, respectively. Four revisions with satellite rods and 1 revision with removal of iliac screw for penetration into the hip joint were performed.

CONCLUSIONS

Surgical strategies for DLS-NF1 were diverse across a range of arthrodesis and surgical approaches, being crucially determined by the location and the severity of dystrophic changes. The LIV being L5 or lower involving the lumbosacral region and pelvis was not rare. Additional posterior satellite rods or supplementary anterior fusion is necessary in cases with insufficient apical screw density. Despite a high incidence of postoperative coronal imbalance, improvement of coronal balance was frequently confirmed during follow-up. Neurological impairment was scarce despite the higher rate of screw malposition.

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Ruobing Xu, Shu Wang, Weishan Li, Zhen Liu, Jiaxin Tang, and Xiaobo Tang

OBJECTIVE

In this study, the authors investigated the involvement of 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in the regulation of peroxisome proliferator-activated receptor–γ (PPARγ) after intracerebral hemorrhage (ICH) and its effects on hemorrhage-induced inflammatory response and oxidative stress in an experimental rodent model.

METHODS

To simulate ICH in a rat model, the authors injected autologous whole blood into the right striatum of male Sprague-Dawley rats. The distribution and expression of 12/15-lipoxygenase (12/15-LOX) were determined by immunohistochemistry and Western blot analysis, respectively. Immunofluorescent double labeling was used to study the cellular localization of 12/15-LOX, and 15(S)-HETE was measured with a 15(S)-HETE enzyme immunoassay kit. Neurological deficits in the animals were assessed through behavioral testing, and apoptotic cell death was determined with terminal deoxynucleotidyl transferase–mediated biotinylated dUTP nick-end labeling.

RESULTS

Rats with ICH had increased expression of 12/15-LOX predominantly in neurons and also in oligodendrocytes, astrocytes, and microglia. Moreover, ICH elevated production of 15(S)-HETE in the brain area ipsilateral to the blood injection. The PPARγ agonist, exogenous 15(S)-HETE, significantly increased PPARγ protein levels and increased PPARγ-regulated gene (i.e., catalase) expression in the ICH rats. Reduced expression of the gene for the proinflammatory protein nuclear factor κB coincided with decreased neuron damage and improved functional recovery from ICH. A PPARγ antagonist, GW9662, reversed the effects of exogenous 15(S)-HETE on the PPARγ-regulated genes.

CONCLUSIONS

The induction of 15(S)-HETE during simulated ICH suggests generation of endogenous signals of neuroprotection. The effects of exogenous 15(S)-HETE on brain hemorrhage–induced inflammatory responses and oxidative stress might be mediated via PPARγ.

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Qinghua Zhao, Benlong Shi, Xu Sun, Zhen Liu, Hao Su, Yang Li, Zezhang Zhu, and Yong Qiu

OBJECTIVE

Intraspinal anomalies associated with congenital scoliosis (CS) complicate the decision-making process for spinal correction surgery in CS patients. Recently, deformity correction surgery without prior prophylactic neurological intervention has been recognized to be safe in CS patients with intact or stable neurological status. However, no case-control study has identified the surgical outcomes and risks of spinal correction surgery in this patient population. The authors sought to investigate the safety and efficacy of spinal correction surgery for CS associated with untreated intraspinal anomalies (split cord malformation [SCM], tethered cord, and/or syringomyelia) with intact or stable neurological status.

METHODS

A group of CS patients with intraspinal anomalies (CS+IA) and another group of CS patients without intraspinal anomalies (CS-IA) undergoing 1-stage posterior correction surgery were retrospectively reviewed. The radiographic and clinical outcomes and postoperative complications were compared between the 2 groups.

RESULTS

There were 57 patients in the CS+IA group and 184 patients in the CS-IA group. No significant difference was observed in age, sex, spinal curve pattern, main Cobb angle, and flexibility of the main curve between the 2 groups (p > 0.05 for all). The postoperative correction rates of the major curve were comparable between the 2 groups (53.5% vs 55.7% for the CS+IA and CS-IA groups, respectively, p > 0.05). No significant difference was observed in the incidence of either implant-related or neurological complications between 2 groups. No patients in the CS+IA group developed neurological complications, whereas 1 patient in the CS-IA group experienced transient weakness of the left lower extremity after surgery.

CONCLUSIONS

Coexisting intraspinal anomalies (SCM, tethered cord, and/or syringomyelia) in CS patients with normal or stable neurological status do not significantly increase the risk of neurological complications of correction surgery. Prophylactic neurosurgical intervention for intraspinal anomalies before correction surgery might be unnecessary for these patients.