Treatment of symptomatic Chiari I malformation by "all-factors-surgery": a report of 194 cases.

PURPOSE: Inadequate decompressions can lead to poor improvement of symptoms in patients with Chiari I malformation (CMI). In this study, the "all-factors-surgery" that including all levels decompressions was performed on symptomatic CMI patients for the snake of eliminating all possible pathogenic factors and reducing the chance of reoperation. METHODS: The "all-factors-surgery" combined operations of posterior fossa decompression, enlarged cranioplasty, duraplasty, cerebellar tonsil partial resection and adhesion release. Total 194 patients from January 2010 to December 2015. The outcome measures included improvement rate of symptoms, patients self-evaluation (improved, unchanged, worsened), Visual Analogue Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, Chicago Chiari Outcome Scale (CCOS) score, the diameter of the syrinx and complications. RESULTS: Postoperative data were collected from the three stages: at discharge, the short-term follow-up (average, 9.39 months), and the long-term follow-up (average, 54.44 months). Patients self-evaluation improvement rate in the three follow-up stages was 92.27%, 90.07% and 85.93%. The VAS scores (mean, 1.49, 1.21, 1.47 vs 3.76) and JOA scores (mean, 15.66, 15.99, 16.10 vs 14.84) were significant difference between the follow-up and pre-operation (P < .05). The CCOS scores of short-term and long-term follow-up were significantly better than that at discharge (mean, 14.75, 14.87 vs 13.68) (P < .05). The diameter of syrinx in each follow-up stage was significantly less than that in pre-operation (mean, 3.39, 1.95, 1.87 vs 5.09) (P < .05). There were no serious complications, and no one asked for reoperation during the follow up. CONCLUSION: Symptomatic CMI patients undergoing "all-factors-surgery" had persistently high rates of symptom relief and rarely needed reoperation.

Risk factor analysis for progressive spinal deformity after resection of intracanal tumors─ a retrospective study of 272 cases.

BACKGROUND: Progressive spinal deformity has become a well-recognized complication of intracanal tumors resection. However, the factors affecting post-operative spinal stability remain to be further research. Here, we described the current largest series of risk factors analysis for progressive spinal deformity following resection of intracanal tumors. METHODS: We retrospectively analyzed the medical records of the patients with resection of intracanal tumors between January 2009 and December 2018. All patients who underwent resection of intracanal tumors performed regular postoperative follow-up were identified and included in the study. Clinical, radiological, surgical, histopathological, and follow-up data were collected. The incidence of postoperative progressive kyphosis or scoliosis was calculated. The statistical relationship between postoperative progressive spinal deformity and radiographic, clinical, and surgical variables was assessed by using univariate tests and multivariate logistic regression analysis. RESULTS: Two hundred seventy-two patients (mean age 42.56 ± 16.18 years) with median preoperative modified McCormick score of 3 met the inclusion criteria. Among them, 7(2.6%)patients were found to have spinal deformity preoperatively, and the extent of spinal deformity in these 7 patients deteriorated after surgery. 36 (13.2%) were new cases of postoperative progressive deformity. The mean duration of follow-up was 21.8 months (median 14 months, range 6-114 months). In subsequent multivariate logistic regression analysis, age ≤ 18 years (p = 0.027), vertebral levels of tumor involvement (p = 0.019) and preoperative spinal deformity(p = 0.008) was the independent risk factors (p < 0.05), increasing the odds of postoperative progressive spinal deformity by 3.94-, 0.69- and 27.11-fold, respectively. CONCLUSIONS: The incidence of postoperative progressive spinal deformity was 15.8%, mostly in these patients who had younger age (≤18 years), tumors involved in multiple segments and preoperative spinal deformity. The risk factors of postoperative progressive spinal deformity warrants serious reconsideration that when performing resection of spinal cord tumors in these patients with such risk factors, the surgeons should consider conducting follow-ups more closely, and when patients suffering from severe symptoms or gradually increased spinal deformity, surgical spinal fusion may be a more suitable choice to reduce the risk of reoperation and improve the prognosis of patients.

Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

BACKGROUND: Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. METHODS: We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. RESULTS: Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. CONCLUSIONS: We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice.

Valproic Acid Arrests Proliferation but Promotes Neuronal Differentiation of Adult Spinal NSPCs from SCI Rats.

Although the adult spinal cord contains a population of multipotent neural stem/precursor cells (NSPCs) exhibiting the potential to replace neurons, endogenous neurogenesis is very limited after spinal cord injury (SCI) because the activated NSPCs primarily differentiate into astrocytes rather than neurons. Valproic acid (VPA), a histone deacetylase inhibitor, exerts multiple pharmacological effects including fate regulation of stem cells. In this study, we cultured adult spinal NSPCs from chronic compressive SCI rats and treated with VPA. In spite of inhibiting the proliferation and arresting in the G0/G1 phase of NSPCs, VPA markedly promoted neuronal differentiation (ß-tubulin III(+) cells) as well as decreased astrocytic differentiation (GFAP(+) cells). Cell cycle regulator p21(Cip/WAF1) and proneural genes Ngn2 and NeuroD1 were increased in the two processes respectively. In vivo, to minimize the possible inhibitory effects of VPA to the proliferation of NSPCs as well as avoid other neuroprotections of VPA in acute phase of SCI, we carried out a delayed intraperitoneal injection of VPA (150 mg/kg/12 h) to SCI rats from day 15 to day 22 after injury. Both of the newborn neuron marker doublecortin and the mature neuron marker neuron-specific nuclear protein were significantly enhanced after VPA treatment in the epicenter and adjacent segments of the injured spinal cord. Although the impaired corticospinal tracks had not significantly improved, Basso-Beattie-Bresnahan scores in VPA treatment group were better than control. Our study provide the first evidence that administration of VPA enhances the neurogenic potential of NSPCs after SCI and reveal the therapeutic value of delayed treatment of VPA to SCI.

Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar.

BACKGROUND: Spinal cord injury (SCI) is characterized by a high rate of disability and imposes a heavy burden on society and patients. SCI can activate glial cells and lead to swelling, hyperplasty, and reactive gliosis, which can severely reduce the space for nerve growth. Glial cells can secrete a large amount of extracellular inhibitory components, thus altering the microenvironment of axon growth. Both these factors seriously impede nerve regeneration. In the present study, we investigate whether curcumin (cur), a phytochemical compound with potent anti-inflammatory effect, plays a role in the repair of SCI. MATERIALS AND METHODS: We established a rat model of SCI and treated the animals with different concentrations of cur. Using behavioral assessment, immunohistochemistry, real-time polymerase chain reaction, Western blotting, and enzyme-linked immunosorbent assay, we detected the intracellular and extracellular components of glial scar and related cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, nuclear factor (NF)-κb, transforming growth factor (TGF)-ß1, TGF-ß2, and sex determining region Y-box (SOX)-9. RESULTS: We found that cur inhibited the expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and NF-κb; reduced the expression of the intracellular components glial fibrillary acidic protein through anti-inflammation; and suppressed the reactive gliosis. Also, cur inhibited the generation of TGF-ß1, TGF-ß2, and SOX-9; decreased the deposition of chondroitin sulfate proteoglycan by inhibiting the transforming growth factors and transcription factor; and improved the microenvironment for nerve growth. Through the joint inhibition of the intracellular and extracellular components of glial scar, cur significantly reduced glial scar volume and improved the Basso, Beattie, and Bresnahan locomotor rating and axon growth. CONCLUSIONS: Our data support a role for curcumin in promoting neural function recovery after SCI by the joint inhibition of the intracellular and extracellular components of glial scar, providing an important strategy for treating SCI.

Hyperbaric oxygen therapy ameliorates acute brain injury after porcine intracerebral hemorrhage at high altitude.

INTRODUCTION: Intracerebral hemorrhage (ICH) at high altitude is not well understood to date. This study investigates the effects of high altitude on ICH, and examines the acute neuroprotection of hyperbaric oxygen (HBO) therapy against high-altitude ICH. METHODS: Minipigs were placed in a hypobaric chamber for 72 h before the operation. ICH was induced by an infusion of autologous arterial blood (3 ml) into the right basal ganglia. Animals in the high-altitude ICH group received HBO therapy (2.5 ATA for 60 min) 30 min after ICH. Blood gas, blood glucose and brain tissue oxygen partial pressure (PbtO2) were monitored continuously for animals from all groups, as were microdialysis products including glucose, lactate, pyruvate and glutamate in perihematomal tissue from 3 to 12 h post-ICH. RESULTS: High-altitude ICH animals showed significantly lower PbtO2, higher lactate/pyruvate ratio (LPR) and glutamate levels than low-altitude ICH animals. More severe neurological deficits, brain edema and neuronal damage were also observed in high-altitude ICH. After HBO therapy, PbtO2 was significantly increased and LPR and glutamate levels were significantly decreased. Brain edema, neurological deficits and neuronal damage were also ameliorated. CONCLUSIONS: The data suggested a more serious disturbance of tissue oxygenation and cerebral metabolism in the acute stage after ICH at high altitude. Early HBO treatment reduced acute brain injury, perhaps through a mechanism involving the amelioration of the derangement of cerebral oxygenation and metabolism following high-altitude ICH.

Complement C5a is detrimental to histological and functional locomotor recovery after spinal cord injury in mice.

Based on the studies on the role of complements C3, C1q and factor B, we hypothesized that complement C5a is detrimental to locomotor recovery at the early stage of secondary injury after spinal cord injury (SCI). To test this hypothesis, we investigated the effect of inhibition of complement C5a receptor (C5aR) by using C5aR antagonist PMX53 (C5aRA) and deficiency of complement C5a receptor (C5aR-/- mice) on histological and locomotor recovery after SCI in mice. We demonstrated that the Basso Mouse Scale scores in the mice injected with C5aRA (C5aRA-mice) at 45min before and 24h after SCI and the C5aR-/- mice were markedly higher than those in the mice treated with saline (Saline-mice) and the C5aR+/+ mice respectively between 7 and 28days after SCI. Also, expression of TNF-α and IL-1ß in C5aRA-mice was significantly lower than that in Saline-mice from 1 to 24h after SCI. In addition, the percentage of microglia/macrophage in C5aRA mice and C5aR-/- mice was significantly lower than those in their corresponding control groups from 1 to 14days after SCI. Furthermore, C5aRA mice and C5aR-/- mice had less GFAP expression in the injured spinal cord epicenter as compared to Saline mice and C5aR+/+ mice at day 28 after SCI. These findings provided evidence that inhibition or deficiency of C5aR could significantly improve histological and functional locomotor recovery after SCI in mice.

Curcumin attenuates acute inflammatory injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway in experimental traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and behavioral impairment, and Toll-like receptor 4 (TLR4) is an important mediator of thiscascade. In the current study, we tested the hypothesis that curcumin, a phytochemical compound with potent anti-inflammatory properties that is extracted from the rhizome Curcuma longa, alleviates acute inflammatory injury mediated by TLR4 following TBI. METHODS: Neurological function, brain water content and cytokine levels were tested in TLR4⁻/⁻ mice subjected to weight-drop contusion injury. Wild-type (WT) mice were injected intraperitoneally with different concentrations of curcumin or vehicle 15 minutes after TBI. At 24 hours post-injury, the activation of microglia/macrophages and TLR4 was detected by immunohistochemistry; neuronal apoptosis was measured by FJB and TUNEL staining; cytokines were assayed by ELISA; and TLR4, MyD88 and NF-κB levels were measured by Western blotting. In vitro, a co-culture system comprised of microglia and neurons was treated with curcumin following lipopolysaccharide (LPS) stimulation. TLR4 expression and morphological activation in microglia and morphological damage to neurons were detected by immunohistochemistry 24 hours post-stimulation. RESULTS: The protein expression of TLR4 in pericontusional tissue reached a maximum at 24 hours post-TBI. Compared with WT mice, TLR4⁻/⁻ mice showed attenuated functional impairment, brain edema and cytokine release post-TBI. In addition to improvement in the above aspects, 100 mg/kg curcumin treatment post-TBI significantly reduced the number of TLR4-positive microglia/macrophages as well as inflammatory mediator release and neuronal apoptosis in WT mice. Furthermore, Western blot analysis indicated that the levels of TLR4 and its known downstream effectors (MyD88, and NF-κB) were also decreased after curcumin treatment. Similar outcomes were observed in the microglia and neuron co-culture following treatment with curcumin after LPS stimulation. LPS increased TLR4 immunoreactivity and morphological activation in microglia and increased neuronal apoptosis, whereas curcumin normalized this upregulation. The increased protein levels of TLR4, MyD88 and NF-κB in microglia were attenuated by curcumin treatment. CONCLUSIONS: Our results suggest that post-injury, curcumin administration may improve patient outcome by reducing acute activation of microglia/macrophages and neuronal apoptosis through a mechanism involving the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages in TBI.

Curcumin increased the differentiation rate of neurons in neural stem cells via wnt signaling in vitro study.

BACKGROUND: The objective of the present study was to clarify the relationship between the neuroprotective effects of curcumin and the classical wnt signaling pathway. METHOD: Using Sprague-Dawley rats at a gestational age of 14.5 d, we isolated neural stem cells from the anterior two-thirds of the fetal rat brain. The neural stem cells were passaged three times using the half media replacement method and identified using cellular immunofluorescence. After passaging for three generations, we cultured cells in media without basic fibroblast growth factor and epidermal growth factor. Then we treated cells in five different ways, including a blank control group, a group treated with IWR1 (10 µmol/L), a group treated with curcumin (500 nmol/L), a group treated with IWR1 + curcumin, and a group treated with dimethyl sulfoxide (10 µmol/L). We then measured the protein and RNA expression levels for wnt3a and ß-catenin using Western blotting and Reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Western-blotting: after the third generation of cells had been treated for 72 h, we observed that wnt3a and ß-catenin expression was significantly increased in the group receiving 500 nmol/L curcumin but not in the other groups. Furthermore, cells in the IWR1-treated group showed decreased wnt3a and ß-catenin expression, and wnt3a and ß-catenin was also decreased in the IWR1 + 500 nmol/L curcumin group. No obvious change was observed in the dimethyl sulfoxide group. RT-PCR: RT-PCR showed similar changes to those observed with the Western blotting experiments. CONCLUSIONS: Our study suggests that curcumin can activate the wnt signaling pathway, which provides evidence that curcumin exhibits a neuroprotective effect through the classical wnt signaling pathway.

Analysis of cerebrospinal fluid flow dynamics and morphology in Chiari I malformation with cine phase-contrast magnetic resonance imaging.

BACKGROUND: To determine cerebrospinal fluid (CSF) dynamics and morphology in Chiari I malformation (CMI) and assess the response to surgery of the posterior cranial fossa, we examined midsagittal imaging along with anterior cervical 2-3 (AC2-3), posterior cervical 2-3 (PC2-3), and aqueduct CSF flow hydrodynamics in axial imaging by using cine phase-contrast magnetic resonance imaging (PCMR). METHOD: We examined 52 patients with CMI, both with and without syringomyelia (SM), pre-/post-surgery, and compared them to 17 healthy volunteers. Statistical analyses included paired t-tests, independent-samples t-tests, binary logistic regression, and crosstab with MedCalc software. RESULTS: Patients with CMI had significantly shorter clivus length and larger tentorial angle than the healthy controls (P = 0.004, P = 0.019, respectively). The AC2-3 cranial/caudal peak velocity (PV), PC2-3 cranial/caudal PV and aqueduct cranial peak PV of patients with CMI were significantly lower than healthy volunteers pre-surgery (P = 0.034 AC2-3 cranial PV, P = 0.000002 AC2-3 caudal PV; P = 0.046 PC2-3 cranial PV, P = 0.015 PC2-3 caudal PV; P = 0.022 aqueduct cranial PV) and increased after surgery (P = 0.024 AC2-3 cranial PV, P = 0.002 AC2-3 caudal PV; P = 0.001 PC2-3 cranial PV, P = 0.032 PC2-3 caudal PV; P = 0.003 aqueduct cranial PV). The aqueduct caudal PV of patients with CMI was higher than that of healthy controls (P = 0.004) and decreased post-surgery (P = 0.012). Patients with pre-surgery PC2-3 cranial PV >2.63 cm/s and aqueduct cranial PV >2.13 cm/s, respectively, experienced primary symptom improvement after surgery. CONCLUSIONS: The innate bony dysontogenesis in patients with CMI contributes to tonsilar ectopia and exacerbates CSF flow obstruction. A pressure gradient that existed between SM and SAS supports the perivascular space theory that is used to explain SM formation. Our findings demonstrate that PCMR maybe a useful tool for predicting patient prognosis.

A novel subtype classification and corresponding surgical strategies for spinal dural cysts -a report of 104 cases.

BACKGROUND: The nomenclature, classification, and surgical approaches for spinal dural cysts (SDCs) remain a subject of controversy. PURPOSE: The present study proposes a novel subtype classification system and corresponding surgical strategies, with the aim of enhancing comprehension of this entity and standardizing surgical treatment. STUDY DESIGN: A retrospective review. PATIENT SAMPLE: A total of 104 patients with SDCs underwent novel subtype classification and corresponding surgical strategies from January 2015 to December 2021. Fifty-four patients who underwent conventional surgery from January 2012 to December 2014 as the control group for preliminary validation. OUTCOME MEASURES: The outcomes are categorized into 4 levels: excellent, good, unchanged, and deteriorated, based on neurological improvement and pain relief. Grades of excellent and good were identified as improvements. Follow-up magnetic resonance imaging and complications were also evaluated. METHODS: Based on the shared pathogenic factor of dural defects, the dural-associated cysts in the spinal canal are uniformly referred to as SDCs. They are further classified into Type 1 (no nerve roots) and Type 2 (containing nerve roots), with 4 additional subtypes based on the shape of the leak and the flow of leakage. The fissure-shaped leak of Type 1a SDCs is directly sutured, whereas the aperture-shaped leak of Type 1b is repaired using a patch. Low-flow leakage of Type 2a is directly sealed using a combination of adipose tissue and fibrin glue, whereas high-flow Type 2b necessitates suturing at the end of the leak to attenuate cerebrospinal fluid flow prior to sealing. RESULTS: The follow-up period averaged 23.8 months. Excellent or good outcomes were achieved in 100%, 88.9%, 100%, and 97.3% for the 4 subtypes respectively. The overall improvement rate of SDCs was 97.1%, which was significantly higher than that of the conventional surgery group (85.2%, p=.008). MRI follow-up showed a significant reduction in cyst size of 100%, 100%, 97.8%, and 97.3% for the 4 subtypes, respectively. The primary complications included pseudomeningocele in 4 cases (3.8%) and delayed wound healing in 5 cases (4.8%). The complication rate was also significantly lower than that of the control group (8.7% vs 24.1%, p=.008). CONCLUSIONS: Subtyping SDCs based on the variation of leaks and leakage can enable more targeted surgical strategies, which are helpful for improving treatment effectiveness and reducing complications.

Role of HCN channels in neuronal hyperexcitability after subarachnoid hemorrhage in rats.

Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH). The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from whole-cell recordings in rat brain slices indicated that (1) perfusion of hemoglobin (Hb)-containing artificial CSF produced neuronal hyperexcitability and inhibited HCN currents in CA1 pyramidal neurons, (2) nitric oxide/Spermine (NO/Sp), a controlled releaser of nitric oxide, attenuated neuronal excitability and enhanced HCN currents in CA1 pyramidal neurons, while L-nitroarginine (L-NNA), an inhibitor of nitric oxide synthase, reduced the HCN currents; and (3) the inhibitory action of Hb on HCN currents was reversed by application of NO/Sp, which also reduced neuronal hyperexcitability; conversely, L-NNA enhanced inhibitory action of Hb on HCN currents. Additionally, Hb perfusion scavenged the production of nitric oxide and decreased the expression of HCN1 subunits in CA1 region. In the rat SAH model, the expression of HCN1, both at mRNA and protein level, decreased in hippocampus CA1 region at 24 h and more pronounced at 72 h after SAH. These observations demonstrated a reduction of HCN channels expression after SAH and Hb reduced HCN currents in hippocampus CA1 pyramidal neurons. Inhibition of HCN channels by Hb may be a novel pathway for inducing the hyperneuronal excitability after SAH.

Deferoxamine attenuates iron-induced long-term neurotoxicity in rats with traumatic brain injury.

This study investigated whether deferoxamine (DFO), an iron chelator attenuates iron-induced toxicity in rats with traumatic brain injury. In this study, three groups of Sprague-Dawley rats (sham, injury and DFO groups) were examined. Rats were killed on day 28 after Morris water maze testing and brains perfused for either non-heme brain binding or hemosiderin staining. Western blotting was used to measure protein levels of ferritin, transferrin and transient receptor potential canonical channel 6 (TRPC6). In TBI rats, there was a significant increase in brain iron on day 28, ferritin L, ferritin H, transferrin and TRPC6 levels were all significantly elevated post-TB1. There were also deficits in spatial learning and memory; however, DFO administration attenuated these effects in TBI rats supporting the notion that DFO may reduce brain injury accentuated by iron overload.

Experimental high-altitude intracerebral hemorrhage in minipigs: histology, behavior, and intracranial pressure in a double-injection model.

BACKGROUND: Specific pathophysiological mechanism in intracerebral hemorrhage (ICH) at high altitude is unclear, and at present, there is no relevant and suitable animal model. METHODS: A hypobaric chamber was used to simulate an altitude of 4,000 m. Autologous arterial blood (3 ml) was slowly infused into the right basal ganglia of minipigs by a double-injection method for producing ICH. RESULTS: The intracranial pressure and neurological score of the high-altitude group were significantly higher than those of the low-altitude (plain) group. The brain water contents and pathological lesions of perihematoma tissue were more severe in the high-altitude group. CONCLUSIONS: The injury resulting from ICH at high altitude was more severe than that in the plain group. This model was able to produce controllable and reproducible hematomas and visible neurological deficits, which may be useful for future studies of the pathophysiology and functional rehabilitation of high-altitude ICH disease.

In vivo magnetic resonance imaging tracking of SPIO-labeled human umbilical cord mesenchymal stem cells.

Human umbilical cord mesenchymal stem cells (hUC-MSCs) can be efficiently labeled by superparamagnetic iron oxide (SPIO) nanoparticles, which produces low signal intensity on magnetic resonance imaging (MRI) in vitro. This study was to evaluate the feasibility of in vivo tracking for hUC-MSCs labeled by SPIO with noninvasive MRI. SPIO was added to cultures at concentrations equivalent to 0, 7, 14, 28, and 56 µg Fe/ml (diluted with DMEM/F12) and incubated for 16 h. Prussian Blue staining was used to determinate the labeling efficiency. Rats were randomly divided into three groups, control group, hUC-MSCs group, and SPIO-labeled hUC-MSCs group. All groups were subjected to spinal cord injury (SCI) by weight drop device. Rats were examined for neurological function. In vivo MRI was used to track SPIO-labeled hUC-MSCs transplanted in rats spinal cord. Survival and migration of hUC-MSCs were also explored using immunofluorescence. Significant improvements in locomotion were observed in the hUC-MSCs groups. There was statistical significance compared with control group. In vivo MRI 1 and 3 weeks after injection showed a large reduction in signal intensity in the region transplanted with SPIO-labeled hUC-MSCs. The images from unlabeled hUC-MSCs showed a smaller reduction in signal intensity. Transplanted hUC-MSCs engrafted within the injured rats spinal cord and survived for at least 8 weeks. In conclusion, hUC-MSCs can survive and migrate in the host spinal cord after transplantation, which promote functional recovery after SCI. Noninvasive imaging of transplanted SPIO-labeled hUC-MSCs is feasible.

G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury.

OBJECTIVE: What underlies the protection of estrogen against spinal cord injury remains largely unclear. Here, we investigated the expression pattern of a new estrogen receptor, G-protein coupled estrogen receptor 1 in the spinal cord and its role in estrogenic protection against spinal cord injury. DESIGN AND SETTINGS: Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals subjected to spinal cord injury were divided into six groups and given vehicle solution, 17ß-estradiol, or G-protein coupled estrogen receptor 1 agonist G-1 at 15 mins and 24 hrs postinjury, or given nuclear estrogen receptor antagonist ICI 182,780 at 1 hr before spinal cord injury followed by 17ß-estradiol administration at 15 mins and 24 hrs postinjury, or given G-protein coupled estrogen receptor 1 specific antisense or random control oligonucleotide at 4 days before spinal cord injury followed by 17ß-estradiol administration at 15 mins and 24 hrs postinjury. MEASUREMENTS: Male Sprague-Dawley rats were subjected to spinal cord injury using a weight-drop injury approach. Immunohistochemical assays were used to observe the distribution and cell-type expression pattern of G-protein coupled estrogen receptor 1. The terminal deoxynucleotidyl transferase dUTP nick-end labeling-staining assay and behavior tests were employed to assess the role of G-protein coupled estrogen receptor 1 in mediating estrogenic protection against spinal cord injury. MAIN RESULTS: We show that G-protein coupled estrogen receptor 1 is mainly distributed in the ventral horn and white matter of the spinal cord, which is totally different from nuclear estrogen receptors. We also show that G-protein coupled estrogen receptor 1 is specifically expressed by neurons, oligodendrocytes, and microglial cells, but not astrocytes. Furthermore, estrogen treatment prevents spinal cord injury-induced apoptotic cell death and enhances functional recovery after spinal cord injury, which can be mimicked by the specific G-protein coupled estrogen receptor 1 agonist G-1 and inhibited by specific knockdown of G-protein coupled estrogen receptor 1 expression, but not pure nuclear ER antagonist ICI 182,780. Finally, we show that estrogen or G-1 up-regulates the protein expression level of G-protein coupled estrogen receptor 1 to intensify estrogenic effects during spinal cord injury. CONCLUSIONS: These results reveal that G-protein coupled estrogen receptor 1 may mediate estrogenic neuroprotection against spinal cord injury, and underline the promising potential of estrogen with its new target G-protein coupled estrogen receptor 1 for the treatment of spinal cord injury patients.

Microsurgical sealing for symptomatic sacral Tarlov cysts: a series of 265 cases.

OBJECTIVE: Tarlov cysts (TCs) are a common cystic entity in the sacral canal, with a reported prevalence between 1.5% and 13.2%; 10%-20% of patients are symptomatic and need appropriate clinical intervention. However, the choice of treatment remains controversial. The goal of this study was to describe a new microsurgical sealing technique for symptomatic sacral TCs (SSTCs) as well as its long-term outcomes. METHODS: Microsurgical sealing was performed using a short incision, leakage coverage with a piece of autologous fat, and cyst sealing with fibrin glue. Postoperative data were collected at three stages: discharge, 1-year follow-up, and a follow-up of 3 years or more. According to the improvement in neurological deficits and degree of pain relief, outcomes were divided into four levels: excellent, good, unchanged, and deteriorated. RESULTS: A total of 265 patients with SSTCs were treated with microsurgical sealing from January 2003 to December 2020. The mean follow-up was 44.69 months. The percentages of patients who benefited from the operation (excellent and good) at the three stages were 87.55%, 84.89%, and 80.73%, respectively, while those who received no benefit (unchanged and deteriorated) were 12.45%, 15.11%, and 19.27%, respectively. Of the patients with postoperative MRI, the cysts were reduced in size or disappeared in 209 patients (94.14%). CSF leakage from the wound was observed in 15 patients, and 4 patients experienced an infection at the incision. There were no cases of new-onset nerve injury or aseptic meningitis after the operation. CONCLUSIONS: SSTC patients undergoing microsurgical sealing had persistently high rates of symptom relief and few postoperative complications. Microsurgical sealing is an effective, simple, and low-risk method for treating SSTCs.

Role of acid-sensing ion channel 1a in the secondary damage of traumatic spinal cord injury.

OBJECTIVE: To determine the cellular and molecular mechanisms by which acid-sensing ion channel 1a (ASIC1a) plays its role in the secondary injury after traumatic spinal cord injury (SCI), and validate the neuroprotective effect of ASIC1a suppression in SCI model in vivo. BACKGROUND: Secondary damage after traumatic SCI contributes to the exacerbation of cellular insult and thereby contributes to spinal cord dysfunction. However, the underlying mechanisms remain largely unknown. Acidosis is commonly involved in the secondary injury process after the injury of central nervous system, but whether ASIC1a is involved in secondary injury after SCI is unclear. METHODS: Male Sprague-Dawley rats were subjected to spinal contusion using a weight-drop injury approach. Western blotting and immunofluorescence assays were used to observe the change of ASIC1a expression after SCI. The TUNEL staining in vivo as well as the cell viability and death assays in spinal neuronal culture were employed to assess the role of ASIC1a in the secondary spinal neuronal injury. The electrophysiological recording and Ca(2+) imaging were performed to reveal the possible underlying mechanism. The antagonists and antisense oligonucleotide for ASIC1a, lesion volume assessment assay and behavior test were used to estimate the therapeutic effect of ASIC1a on SCI. RESULTS: We show that ASIC1a expression is markedly increased in the peri-injury zone after traumatic SCI. Consistent with the change of ASIC1a expression in injured spinal neurons, both ASIC1a-mediated whole-cell currents and ASIC1a-mediated Ca(2+) entry are significantly enhanced after injury. We also show that increased activity of ASIC1a contributes to SCI-induced neuronal death. Importantly, our results indicate that down-regulation of ASIC1a by antagonists or antisense oligonucleotide reduces tissue damage and promotes the recovery of neurological function after SCI. CONCLUSION: This study reveals a cellular and molecular mechanism by which ASIC1a is involved in the secondary damage process after traumatic SCI. Our results suggest that blockade of Ca(2+) -permeable ASIC1a may be a potential neuroprotection strategy for the treatment of SCI patients.

Immediate splenectomy decreases mortality and improves cognitive function of rats after severe traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major health problem all over the world. It frequently causes a considerable social burden because of its high incidence of death and long-term disability, especially in the case of severe TBI. Recent studies revealed that the spleen might contribute to secondary brain injury after ischemia or intracerebral hemorrhage. The purpose of this study was to evaluate the significance of the spleen in traumatic brain edema after severe TBI. METHODS: We established a severe TBI model with rats and performed splenectomy to observe the mortality, brain water content, cognitive function (water maze), and cytokines levels, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, and IL-10, in the blood plasma (enzyme-linked immunosorbent assay) and their mRNA expression levels in injured brain tissue (quantitative reverse transcriptase-polymerase chain reaction). RESULTS: The immediate splenectomy after TBI significantly decreased the death rate from 35.42% to 14.89% and eliminated the brain water content of the injured brain, especially at days 2 and 3. The Morris water maze assessment showed an improved spatial reference memory in rats that underwent both TBI and splenectomy when compared with those in the TBI group, 4 weeks later. Splenectomy reduced the IL-1ß, TNF-α, and IL-6 contents in the blood serum after TBI, and the mRNA expression levels of IL-1ß, TNF-α, and IL-6 in the ipsilateral brain tissue also decreased. CONCLUSIONS: Our study demonstrates that splenectomy has a protective effect on rats with severe TBI by inhibiting proinflammatory cytokines, including IL-1ß, TNF-α, and IL-6, both systematically and locally in the injured brain, hence leading to a decreased mortality and improved cognitive function.

Endovascular embolization for intracranial aneurysms: report of 162 cases.

OBJECTIVE: to summarize the experiences of endovascular embolization for intracranial aneurysms and emphatically discuss techniques, complications and preventions. METHODS: 171 aneurysms in 162 patients were treated by detachable coil embolization. Among them, 38 cases were treated by GDC, 35 by DCS, and 89 by EDC. RESULTS: 137 aneurysms were 100% occluded, 27 were 90-95% occluded, and 7 were 80% occluded. Complications associated with operation occurred in nine patients. The coil escaping from the sac of aneurysm into its parent artery was seen in five patients. Six patients suffered from rupture of aneurysm during the operation. Serious vasospasm was seen in five patients. Two patients died of complications. CONCLUSIONS: endovascular embolization is a safe, effective and minimally invasive method for treating intracranial aneurysms. Choosing exact embolization techniques is very important to improve the therapeutic effect and decrease the complications of embolization of intracranial aneurysms.