Syringo-Subarachnoid Shunt with Tube Versus T-Tube via the Dorsal Root Entry Zone Approach for Eccentric Syringomyelia.

OBJECTIVE: This study compared the clinical therapeutic efficacy of syringo-subarachnoid shunt placement with direct tube and T-tube via the dorsal root entry zone (DREZ) approach for treatment of eccentric syringomyelia. METHODS: A retrospective study was performed of 41 patients with idiopathic or secondary eccentric syringomyelia from November 2011 to December 2022. Syringo-subarachnoid shunt placement with direct tube or T-tube via the DREZ approach was performed. The modified Japanese Orthopaedic Association low back pain scale was used to investigate the severity of clinical symptoms. Magnetic resonance imaging was used to investigate therapeutic efficacy（reduction of the cavity volume by >10% was considered an improvement and 50% was considered a significant improvement). RESULTS: Incision length of the spinal cortex in the direct tube group was shorter than in the T-tube group (3.10 ± 0.28 cm vs. 5.03 ± 0.19 cm), with a significant difference between the 2 groups (t = -52.56, P < 0.001). Modified Japanese Orthopaedic Association score 3 months postoperatively was significantly better than the preoperative score in both the direct tube group（t = 40.954, P < 0.001） and the T-tube group（t = 24.769, P < 0.001）. Statistical comparison revealed there was no difference in imaging improvement between the direct tube group and T-tube group 3 months (χ2 = 0.20, P = 0.655) and 12 months (χ2 = 0.21, P = 0.647) postoperatively. CONCLUSIONS: Syringo-subarachnoid shunt placement with direct tube via the DREZ approach for treatment of eccentric syringomyelia is safer than with T-tube via the DREZ approach due to smaller incision length and less of a space-occupying effect with same therapeutic efficacy.

Neuroprotective effect of baicalin on focal cerebral ischemia in rats.

Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups: ischemia (cerebral ischemia and reperfusion), valproic acid (cerebral ischemia and reperfusion + three intraperitoneal injections of valproic acid; positive control), and baicalin (cerebral ischemia and reperfusion + intraperitoneal injection of baicalin for 21 days). Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.

Regulation of Gli2 stability by deubiquitinase OTUB2.

The transcription factor Gli2 plays crucial roles in the transduction of Hedgehog (Hh) signals, yet the mechanisms that control Gli2 degradation remain unclear. Here we have identified the eubiquitinating enzyme otubain2 (OTUB2) as a regulator of Gli2 protein degradation. We found that OTUB2 was coimmunoprecipitated with Gli2. Knockdown of OTUB2 decreased Gli2 protein level while the proteasome inhibitor MG-132 treatment restored Gli2 expression. Additionally, OTUB2 overexpression stabilized Gli2 protein in U2OS cells and extended the half-life of Gli2. We also found that knockdown of OTUB2 reduced deubiquitination of Gli2 in vivo. In vitro deubiquitination assay showed that ubiquitinated Gli2 was decreased by wild-type OTUB2 but not OTUB2 mutations. We also found that OTUB2 knockdown suppressed the ALP activity and the expression of the common markers BMP2 and RUNX2 during osteogenesis of MSCs in response to Shh and Smo agonists, which indicated OTUB2 may have effect on osteogenic differentiation by regulating Hh signaling.

Lipoprotein-biomimetic nanostructure enables efficient targeting delivery of siRNA to Ras-activated glioblastoma cells via macropinocytosis.

Hyperactivated Ras regulates many oncogenic pathways in several malignant human cancers including glioblastoma and it is an attractive target for cancer therapies. Ras activation in cancer cells drives protein internalization via macropinocytosis as a key nutrient-gaining process. By utilizing this unique endocytosis pathway, here we create a biologically inspired nanostructure that can induce cancer cells to 'drink drugs' for targeting activating transcription factor-5 (ATF5), an overexpressed anti-apoptotic transcription factor in glioblastoma. Apolipoprotein E3-reconstituted high-density lipoprotein is used to encapsulate the siRNA-loaded calcium phosphate core and facilitate it to penetrate the blood-brain barrier, thus targeting the glioblastoma cells in a macropinocytosis-dependent manner. The nanostructure carrying ATF5 siRNA exerts remarkable RNA-interfering efficiency, increases glioblastoma cell apoptosis and inhibits tumour cell growth both in vitro and in xenograft tumour models. This strategy of targeting the macropinocytosis caused by Ras activation provides a nanoparticle-based approach for precision therapy in glioblastoma and other Ras-activated cancers.

Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia.

Ischemic postconditioning, including early and delayed ischemic postconditioning, has been recognized as a simple and promising strategy in the treatment of stroke. However, the effects of the combination of early and delayed ischemic postconditioning, and the mechanisms underlying these effects, remain unclear. The aim of the present study was to determine whether the combination of early and delayed ischemic postconditioning offers greater protection against stroke, and enhances the production of brain­derived neurotrophic factor (BDNF). A combination of early and delayed ischemic postconditioning was established by repeated, transient occlusion and reperfusion of the ipsilateral common carotid artery in a rat model of middle cerebral artery occlusion. Infarct size, motor function, cerebral blood flow and brain edema were then evaluated, in order to confirm the effects of combinative ischemic postconditioning. TUNEL staining was used to analyze the rate of apoptosis of cells in the penumbral area. BDNF, extracellular signal­regulated kinases 1/2 (ERK1/2) and cAMP response element­binding protein (CREB) expression was detected using immunofluorescence staining and western blot analysis. The results of the present study indicated that the combination of early and delayed ischemic postconditioning further reduced the infarct volume, stabilized cerebral blood disturbance and attenuated neuronal apoptosis, compared with either alone. However, combinative postconditioning exerted the same effect on neurological function and brain edema, compared with early or delayed ischemic postconditioning alone. Further investigation indicated that combinative ischemic postconditioning increased the expression of BDNF, and a significantly higher number of BDNF­positive cells was observed in neurons and astrocytes from the combined group than in the early or delayed groups. Combinative ischemic postconditioning also induced the phosphorylation of ERK1/2 and CREB in the cortex, following focal ischemia. The results of the present study suggest that the combination of early and delayed ischemic postconditioning may further reduce brain ischemic reperfusion injury following focal ischemia, compared with either treatment alone. In addition, it induces the production of BDNF in neurons and astrocytes. Furthermore, the effects of combinative ischemic postconditioning may be mediated by the activation of ERK1/2 and CREB.

IDH1R¹³²H decreases the proliferation of U87 glioma cells through upregulation of microRNA-128a.

Mutations in isocitrate dehydrogenase 1 (IDH1) are found in >70% of secondary glioblastomas and lower-grade gliomas (grades II-III). Among the numerous phenotypic differences between IDH1 mutant and wild-type glioma patients, the most salient is an improved survival rate for patients with a mutation. MicroRNAs (miRNAs) are a class of small, non­coding, single­stranded RNAs that can negatively regulate gene expression at the post­transcriptional level, predominantly by binding to the 3'­untranslated region of their target mRNAs. The dysregulated expression of several miRNAs has been reported to modulate glioma progression; however, it is unclear whether mutations in IDH1 regulate glioma cell proliferation through miRNA dysregulation. In the present study, stable overexpression of IDH1WT or IDH1R132H was established in the U87 glioma cell line. It was found that IDH1R132H decreased cell proliferation of U87 glioma cells by inducing the expression of the miRNA miR­128a. This process was dependent on the transcription factor hypoxia inducible factor­1α (HIF­1α), which binds to a hypoxia response element in the promoter of miR­128a. Furthermore, miR­128a negatively regulated the expression of B­cell­specific Moloney murine leukemia virus integration site 1 protein (Bmi­1), which is involved in suppressing cell proliferation. These findings suggest that the IDH1R132H­HIF­1α­miR­128a­Bmi­1 pathway is involved in glioma cell proliferation.

5'-adenosine monophosphate-induced hypothermia attenuates brain ischemia/reperfusion injury in a rat model by inhibiting the inflammatory response.

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5'-adenosine monophosphate (5'-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5'-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5'-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia.

The diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions.

The objective of this study was to investigate the diagnosis and surgical treatment of central brain herniations caused by traumatic bifrontal contusions. A total of 63 patients (45 men and 18 women; mean age of 43 years with a range from 20 to 72 years) who suffered from traumatic bifrontal contusions between January 2007 and December 2012 were inspected. The clinical and imaging results were studied for all patients, and we found that swelling of the mesencephalon and a downward shift of the bilateral red nucleus were significant signs of central brain herniation in the image of magnetic resonance imaging. All patients were given a simultaneous bilateral craniotomy for balanced decompressive surgery. The Glasgow Outcome Scale was used to monitor the patients during the follow-up period, which lasted from 6 to 52 months with a mean of 22 months. At the termination of the follow-up period, the following Glasgow Outcome Scale scores were obtained: 14 patients scored 5 points, 22 patients scored 4 points, 7 patients scored 3 points, 13 patients scored 2 points, and 7 patients scored 1 point. Therefore, our study suggested that an early magnetic resonance imaging scan could result in a more timely diagnosis of central brain herniation, and simultaneous bilateral craniotomy was found to be one of the best treatments for central brain herniation to improve patient outcomes.

Endovascular treatment of the extracranial carotid pseudoaneurysms resulting from stab penetrating injury using overlapping bare stents.

Injury pertaining to the common carotid artery may result in complete or partial arterial transection, pseudoaneurysms, or arteriovenous connections. Endovascular treatment option of the pseudoaneurysm has already been established with favorable success rate and minimal morbidity. Our purpose is to report one 18-year-old male patient having 2 traumatic pseudoaneurysms as a result of penetrating stab injury in the extracranial common carotid. The patient was successfully treated using 2 overlapping bare-metal stents. The 2 common carotid pseudoaneurysms had different degree inflow angles defined as the space between the lines indicating the direction of blood flow from the parent artery and through the aneurysmal neck to the dome. Computed tomography angiography was utilized to follow the evolution of the pseudoaneurysms until total occlusion was demonstrated. The treatment modality used in this report represents an alternative approach of the endovascular treatment for the extracranial carotid pseudoaneurysm.

Migration of neural stem cells to ischemic brain regions in ischemic stroke in rats.

An established rat model of ischemic stroke, produced by temporary middle cerebral artery occlusion and reperfusion (MCAO/R), was used in the evaluation of organ migration of intra-arterial (IA) transplantation of neural stem cells (NSCs). Immediately after transplantation, ischemic rats (n=8) transplanted with either NSCs (MCAO/R+NSC group) or NSC growth medium (MCAO/R+medium group) exhibited neurological dysfunction but rats in a sham+NSCs group (n=5) did not. During the post-operative period, neurological function improved to a similar extent in both MCAO/R groups. At 10 and 14 days post-transplantation, neurological function in the MCAO/R+NSC group was superior to that in the MCAO/R+medium group (p<0.001). Hematoxylin-eosin staining showed neuronal degeneration and necrosis in ischemic rats. Immunofluorescence staining revealed that NSCs had migrated to the frontal and parietal lobes, caudate, and putamen. Some cells had begun differentiating into neurons and astrocytes. Rat NSCs can migrate into the ischemic region, survive, and differentiate into astrocytes and neurons, and thereby potentially improve neurologic function after cerebral ischemia.

Activations of GABAergic signaling, HSP70 and MAPK cascades are involved in baicalin's neuroprotection against gerbil global ischemia/reperfusion injury.

Baicalin, a flavonoid compound isolated from the plant Scutellaria baicalensis Georgi, is known as a protective agent against delayed neuronal cell death after ischemia/reperfusion. To investigate the neuroprotective mechanism of baicalin, the present study was conducted to explore whether the alterations of GABAergic signaling, heat shock protein 70 (HSP70) and mitogen-activated protein kinases (MAPKs) were involved in its neuroprotection on gerbils global ischemia. The bilateral carotid arteries were occluded by 5 min and baicalin at the dose of 200 mg/kg was intraperitoneally injected into the gerbils immediately after cerebral ischemia. Seven days after reperfusion, neurological deficit was scored and changes in hippocampal neuronal cell death were assessed by Nissl staining as well as NeuN immunohistochemistry. The mRNA and protein expressions of GABAergic signal molecules (GABA(A)R α1, GABA(A)R γ2, KCC2 and NKCC1) were determined in ischemic hippocampus by real-time RT-PCR and Western blot, respectively. In addition, HSP70 and MAPKs cascades (ERK, JNK and p38) were also detected using western blot assay. Our results illustrated that baicalin treatment significantly facilitated neurological function, suppressed the ischemia-induced neuronal damage. Besides, administration of baicalin also caused a striking increase of GABA(A)R α1, GABA(A)R γ2 and KCC2 together with the decrease of NKCC1 at mRNA and protein levels in gerbils hippocampus following an ischemic insult. Furthermore, the protein expressions of HSP70 and phosphorylated ERK (p-ERK) were evidently augmented while the phosphorylated JNK (p-JNK) and phosphorylated p38 (p-p38) were strikingly diminished in ischemic gerbils with baicalin treatment. These findings suggest that baicalin activates GABAergic signaling, HSP70 and MAPKs cascades in global ischemia, which may be a mechanism underlying the baicalin's neuroprotection.

Risk factors related to aneurysmal rebleeding.

OBJECTIVE: Rebleeding from ruptured intracranial aneurysms is a major cause of death and disability. The aim of this study was to investigate the incidence of rebleeding and the risk factors related to rebleeding before early aneurysm repair. METHODS: The incidence of rebleeding, demographic data, and clinical data from 326 patients with aneurysmal subarachnoid hemorrhage (SAH) were retrospectively collected. All clinical variables were examined by univariate analysis, and a binary logistic regression analysis was performed to identify the risk factors related to rebleeding. RESULTS: Rebleeding occurred in 70 (21.5%) of the 326 aneurysm patients during transfer or during the in-hospital stay (within 72 hours); 24 episodes (34.3%) occurred within 3 hours, and 44 episodes (62.9%) occurred within 6 hours after the initial SAH. Univariate analysis showed that there were significant differences between the rebleeding and nonrebleeding patients in terms of age, aneurysm size, systolic arterial blood pressure (SBP), Hunt-Hess grade and outcome at discharge. The binary logistic regression analysis revealed that age (odds ratio [OR] = 1.167), aneurysm size (OR = 1.624), SBP (OR = 3.338), and Hunt-Hess grade (OR = 2.512) were independent risk factors for aneurysmal rebleeding (for each P < 0.05). CONCLUSIONS: The incidence of early aneurysmal rebleeding within hours after the initial SAH is high during transfer or during the in-hospital stay. Advanced age, an aneurysm size larger than 10 mm, SBP higher than 160 mmHg, and poor Hunt-Hess grade were independent risk factors for aneurysmal rebleeding. The importance of early aneurysm repair should be emphasized because aneurysmal rebleeding contributes to a poor outcome.

The up-regulation of voltage-gated sodium channel Nav1.6 expression following fluid percussion traumatic brain injury in rats.

BACKGROUND: The influx of Na and the depolarization mediated by voltage-gated sodium channels (VGSCs) is an early event in traumatic brain injury (TBI) induced cellular abnormalities and is therefore well positioned as an upstream target for pharmacologic modulation of the pathological responses to TBI. Alteration in the expression of the VGSC alpha-subunit has occurred in a variety of neuropathological states including focal cerebral ischemia, spinal injury, and epilepsy. OBJECTIVE: In this study, changes in Nav1.6 mRNA and protein expression were investigated in rat hippocampus after TBI. METHODS: Forty-eight adult male Sprague Dawley rats were randomly assigned to control or TBI groups. TBI was induced with a lateral fluid percussion device. Expression of mRNA and protein for Nav1.6 in the bilateral hippocampus was examined at 2, 12, 24, and 72 hours after injury by real-time quantitative polymerase chain reaction and Western blot. Immunofluorescence was performed to localize the expression of Nav1.6 protein in the hippocampus. RESULTS: Expression of >Nav1.6 mRNA was significantly up-regulated in the bilateral hippocampus at 2 and 12 hours post-TBI. Significant up-regulation of Nav1.6 protein was identified in the ipsilateral hippocampus from 2 to 72 hours post-TBI and in the contralateral hippocampus from 2 to 24 hours post-TBI. Expression of Nav1.6 occurred predominantly in neurons in the hippocampus. CONCLUSION: Results of the study showed significant up-regulation of mRNA and protein for Nav1.6 in rat hippocampal neurons after TBI.

[Experimental study on apoptosis induced by elemene in glioma cells].

BACKGROUND & OBJECTIVE: Elemene, isolated from the Chinese medicinal herb Rhizoma Zedoariae, was shown to exhibit antitumor activity. Our previous studies showed that elemene had a markedly antineoplastic activity on glioma. This study was designed to investigate the proliferation inhibitory effect and the apoptosis-inducing activity of elemene on glioma cells. METHODS: The effects of elemene on cell proliferation were studied in vitro by using (3)H-TdR incorporation. The morphological alterations were confirmed by Hoechst 33258/PI staining. The apoptosis was evaluated by flow cytometry analysis and agarose gel electrophoresis. RESULTS: Elemene exhibited a marked antiproliferative effect on rat glioma cell C6 and human glioma cell SHG-44. The fifty percent inhibition concentration (IC(50)) of elemene against glioma cell lines at different time points (D1-D4) by (3)H-TdR incorporation was C6 7.33-11.02 mg/L, SHG-44 13.29-27.16 mg/L. At the same concentration, human glioma cell line SHG-44 was found to be less sensitive to elemene compared to rodent cell line C6. The characteristic nucleolus alternations under fluorescent microscope included condensation of chromatin arranged under the nuclear membrane and apoptotic bodies, with a low nuclear/cytoplasmic ratio. In flow cytometry analysis, a typical subdiploid peak before Phase G(0)/G(1) (apoptotic peak) was detected in DNA frequency distribution histograms. Also the apoptosis in glioma cells was confirmed by DNA ladder formation on gel electrophoresis. CONCLUSION: Elemene exhibited a marked antiproliferative effect on glioma cells, and it could induce apoptosis in vitro.

Clinical analysis of massive hemispheric infarction treated with moderate hypothermia.

The potential of hypothermia in reducing neuronal damage has been demonstrated in several animal models of focal cerebral ischemia. The feasibility and safety of this technique for acute stroke has been only examined in one study, describing a total of 25 patients. We analyzed the data from 50 consecutive patients with acute stroke treated with moderate hypothermia in neurocritical care units of 4 university clinics to evaluate the feasibility and safety of moderate hypothermia.