The status of cerebral perfusion and its restoration level play a vital role in the prognosis and clinical decision making of many neurosurgical diseases. As such, gold standard methods including CT, MR and ICP monitoring, which can indicate and measure cerebral perfusion and restoration, have been widely adopted to evaluate whether or not a patient has recovered from neurofunctional disabilities. This robust combination of methods, however, is confronted with a growing number of contradictions in recent years due to its inability to measure the status of cerebral reperfusion in microvasculature level, even though this has been shown to determine neurofunctional restoration as well or even better. To this date, nevertheless, we have very limited imaging methods that could evaluate human cerebral microperfusion both safely and accurately under most neurosur-gical conditions. We herein report a new method of acquiring a patient's cerebral microperfusion status non-invasively which could display the precise distribution of microvasculature in deep cerebral regions with a resolution of similar to 30 mu m, using everyday bed-side ultrasonography combined with a computerized super-resolution reconstruction algorithm. Using this imaging modality, we found that a patient's cerebral microperfusion might not be improved by some routine administrations even though the gold standard method had yielded the opposite conclusions. Our imaging modality retains the safe, portable feature of ordinary ultrasonography while possesses the extraordinary super-resolution nature, which enables an efficient, precise diagnosis of cerebral perfusion. Most importantly, the super resolution nature of this method may also facilitate early-stage evaluation of a patient's neurofunctional restoration level and avoid overoptimistic conclusions from conventional angi-ography or ICP monitoring.

Background:Rabbit elastase-induced aneurysms have widely been used to test various endovascular materials over the past two decades. However, wide-necked aneurysms cannot be stably constructed.Objective:The purpose of the study was to increase the neck width of the elastase-induced aneurysm model in rabbits via an improved surgical technique with two temporary clips.Materials and Methods:Fifty-four elastase-induced aneurysms in rabbits were successfully created. Group 1 was (n = 34) composed of cases in which two temporary aneurysm clips were placed closely medially and laterally to the origin of the right common carotid artery (RCCA), respectively. Group 2 (n = 20) included cases in which a single temporary aneurysm clip was placed crossed the origin of RCCA. Digital subtraction angiography (DSA) was performed before and immediately after elastase incubation and 3 weeks later. The diameter of the origin of RCCA before and immediately after elastase incubation and aneurysm sizes of the two groups were measured and compared. Moreover, the correlation analysis was performed between the diameter of the origin of RCCA immediately after elastase incubation and aneurysm neck width.Results:The mean aneurysm neck and dome width of group 1 were both significantly larger than that of group 2 (p-value < 0.001 and p-value = 0.005, respectively). Moreover, the proportion of wide-necked aneurysms (neck width ≥4 mm) in group 1 was significantly larger than that in group 2 (p-value = 0.004) and the mean dome to neck ratio (D/N) of group 1 was smaller than that of group 2 (p-value = 0.008). Furthermore, there was a positive correlation between the diameter of the origin of RCCA immediately after elastase incubation and aneurysm neck width.Conclusion:The improved surgical technique with two temporary clips, focusing on the direct contact of elastase with the origin of RCCA, could increase the neck width of elastase-induced aneurysm models in rabbits.

Background: Alzheimer’s disease (AD), a neurodegenerative disease showing multiple complex pathomechanism alterations, has affected the normal life of many old people. It is urgent to find an effective medicine for AD. Ginsenoside Rb1 (Rb1) is the main component of panax notoginseng saponins, a famous Chinese herbal medicine, and is expected to be a useful drug in the treatment of AD. This study mainly explored the potential effects of Rb1 in model of AD in vivo and in vitro, and investigated the possible mechanisms. Materials and methods: We studied the neuroprotective effect of Rb1 in transgenic mouse animal model and cell AD model in vitro. The cognitive function of APP/PS1 mice was measured in Morris water maze and Novel Object Recognition. Electrophysiological patch clamp recording and electrophysiology were used to nerve excitability. Further, the expression of proteins of Nav1.2 and Nav1.6 were used by Western blot. Results: We found that Rb1 treatment significantly improved the cognitive and memory loss, and reversed the hyperexcitability by altering the expressions of Nav1.2 and Nav1.6 of APP/PS1 mice. Further, Rb1 improved the hyperexcitability induced by Aβ1-42-injured neurons, which might be associated with alteration of the expressions of Nav1.2 and Nav1.6. As we expect, Rb1 attenuated Aβ1-42-induced injury in primary neurons. Conclusion: Our data showed that Rb1 played a critical role in improvement of the cognitive deficit and abnormal excitability of AD by regulating Nav1.2 and Nav1.6 expressions. Thus, Rb1 shows protective effects on AD models and may be a potential candidate for AD treatment.

Alzheimer disease is characterized by a progressive cognitive deficit and may be associated with an aberrant hyperexcitability of the neuronal network. Notoginsenoside R1 (R1), a major activity ingredient from Panax notoginseng, has demonstrated favorable changes in neuronal plasticity and induced neuroprotective effects in brain injuries, resulting from various disorders, however, the underlying mechanisms are still not well understood. In the present study, we aimed to explore the possible neuroprotective effects induced by R1 in a mouse model of AD and the mechanisms underlying these effects. Treatment with R1 significantly improved learning and memory functions and redressed neuronal hyperexcitability in amyloid precursor protein/presenilin-1 mice by altering the numbers and/or distribution of the members of voltage-gated sodium channels (Nav). Moreover, we determined whether R1 contributed to the regulation of neuronal excitability in Aβ-42-injured cells. Results of our study demonstrated that treatment with R1 rescued Aβ1-42-induced injured neurons by increasing cell viability. R1-induced alleviation in neuronal hyperexcitability might be associated with reduced Navβ2 cleavage, which partially reversed the abnormal distribution of Nav1.1α. These results suggested that R1 played a vital role in the recovery of Aβ1-42-induced neuronal injury and hyperexcitability, which is regulated by Nav proteins. Therefore, R1 may be a promising candidate in the treatment of AD.

[目的]探讨体位变化对高血压脑出血术后病人颅内压和脑灌注压的影响。[方法]2012年8月—2016年12月选择在我院诊治的高血压脑出血病人66例,根据随机数字表法分为观察组与对照组,所有病人都行开颅去大骨瓣减压手术,对照组给予传统手术体位干预,观察组给予抬高体位干预,记录颅内压和脑灌注压的变化情况。[结果]观察组开骨瓣时与清除血肿后的颅内压和脑灌注压均低于对照组（P＜0.05）,术后第14天观察组总有效率为97.0%,高于对照组（81.8%,P＜0.05）,且观察组卒中量表（NIHSS）评分为2.22分±0.84分,对照组NIHSS评分为4.11分±0.52分,均低于术前的7.30分±1.11分和7.33分±1.19分。[结论]术中抬高手术床头30°,有利于降低高血压脑出血术后病人颅内压和脑灌注压,从而提高预后疗效,促进神经功能恢复。

BACKGROUND This study aimed to evaluate the effects of electro-acupuncture (EA) on neuroplasticity associated with the expressions of neurotrophic factors (NTFs) and their receptors in rats subjected to spinal cord transection (SCT). MATERIAL AND METHODS A total of 144 rats were randomly divided into 3 groups (n=48 per group): sham-operated group, SCT group, and EA (electro-acupuncture) group. Rats in SCT and EA groups received spinal cord transection at T10-T11 vertebral levels. Then, EA group rats received EA treatment. Reverse transcription polymerase chain reaction was used to detect NTFs and receptors at the mRNA level. In situ hybridization (ISH) and immunohistochemistry (IHC) were used to detect the expression of NTFs and their receptors. Basso, Beattie, Bresnahan (BBB) scores and cortical somato-sensory evoked potentials (CSEP) were evaluated to assess the recovery of motor and sensory functions. We also measured BDA (Biotinylated dextran amine) axonal tracing, CGRP (Calcitonin gene-related peptide), GAP-43 (Growth-associated protein), and synaptophysin immunohistochemistry (IHC). RESULTS EA treatment led to obvious improvement in hindlimb locomotor and sensory functions. CNTF, FGF-2, and TrkB mRNA were significantly upregulated, while NGF, PDGF, TGF-b1, IGF-1, TrkA, and TrkC mRNA were concomitantly downregulated in the caudal spinal segment (CSS) following EA. Immunohistochemistry demonstrated an increased number of CGRP fibers, GAP-43, and synaptophysin profiles in the CSS in the EA rats. CONCLUSIONS EA may promote the recovery of neuroplasticity in rats subjected to SCT. This could be attributed to the systematic regulation of NTFs and their receptors after EA.

Rho-kinase dimerization is essential for its kinase activity and biological function; disruption of the dimerization has recently been established as a new and promising therapeutics strategy for cerebrovascular malformation (CM). Based on Rho-kinase dimer crystal structure we herein combined in silico analysis and in vitro assay to rationally derive self-inhibitory peptides from the dimerization interface. Three peptides namely Hlp1, Hlp2 and Hlp3 were successfully designed that have potential capability to rebind at the dimerization domain of Rho-kinase. Molecular dynamics (MD) simulations revealed that these peptides are helically structured when bound to Rho-kinase, but exhibit partially intrinsic disorder in unbound state. Binding free energy (BFE) analysis suggested that the peptides have a satisfactory energetic profile to interact with Rho-kinase. The computational findings were then substantiated by fluorescence anisotropy assays, conforming that the helical peptides can bind tightly to Rho-kinase with affinity KD at micromolar level. These designed peptides are considered as lead molecular entities that can be further modified and optimized to obtain more potent peptidomimetics as self-competitors to disrupt Rho-kinase dimerization in CM.

Objective The surgical treatment and curative effect of transcranial subfrontal unroofing retrobular tumor resection are introduced and the prognosis is discussed.Methods The clinical data of 13 patients with retrobular tumors treated in our department were collected retrospectively.All the patients underwent surgery through subfrontal unroofing approach to discuss the surgical challenges,which involved tumor removal,visual function preservation and cosmetic reconstruction.Results Total resection of the tumors was achieved in 9 cases( 8 angioma and 1 optic nerve neurinoma),subtotal resection in 2 optic nerve neurinoma cases,and the partial resection in 1pserdotumor and 1 hamartoma.Seven patients were followed-up for 6 months( 6 patients was lost during follow-up).Of 7 patients,the visual acuity was improved in 6 patients and remained unchanged in 1 patient.Conclusion Retrobular tumor can be treated safely by transcranial approaches which provides a better exposure of the orbital cavity and tumors.

目的 通过对进展性脑挫伤患者的凝血指标进行动态检测,探讨在进展过程中关键凝血指标的变化.方法 对95例进展性脑挫伤患者进行临床资料分析,检测伤后24h～7d内格拉斯哥昏迷评分(GCS)、凝血酶原时间(PT)、激活部分凝血酶原时间(APTT)、纤维蛋白原含量(FIB)、D-二聚体浓度(D-dimer)、纤维蛋白降解产物(FDP)以及其变化趋势.分析其中与死亡率、格拉斯哥预后评分(GOS)相关的危险因素.结果 进展性脑挫伤各组患者中入院评分、D-二聚体及纤维蛋白原含量与死亡率、GOS评分相关.结论 凝血指标对进展性脑挫伤患者预后判断具有临床指导意义,入院评分越低,D-二聚体浓度越高,纤维蛋白原含量越高预后越差.其中以双额叶及颞叶部位进展性脑挫伤预后较差.

AbstractThis meta-analysis examined whether early decompressive craniectomy (DC) can improve control of intracranial pressure (ICP) and mortality in patients with traumatic brain injury (TBI).Medline, Cochrane, EMBASE, and Google Scholar databases were searched until May 14, 2015, using the following terms: traumatic brain injury, refractory intracranial hypertension, high intracranial pressure, craniectomy, standard care, and medical management. Randomized controlled trials in which patients with TBI received DC and non-DC medical treatments were included.Of the 84 articles identified, 8 studies were selected for review, with 3 randomized controlled trials s having a total of 256 patients (123 DCs, 133 non-DCs) included in the meta-analysis. Patients receiving DC had a significantly greater reduction of ICP and shorter hospital stay. They also seemed to have lower odds of death than patients receiving only medical management, but the P value did not reach significance (pooled odds ratio 0.531, 95% confidence interval 0.209–1.350, Z = 1.95, P = 0.183) with respect to the effect on overall mortality; a separate analysis of 3 retrospective studies yielded a similar result.Whereas DC might effectively reduce ICP and shorten hospital stay in patients with TBI, its effect in decreasing mortality has not reached statistical significance.

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1-5 and L7-S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

Many studies of protein expression after traumatic brain injury (TBI) have identified biomarkers for diagnosing or determining the prognosis of TBI. In this study, we searched for additional protein markers of TBI using a fluid perfusion impact device to model TBI in S-D rats. Two-dimensional gel electrophoresis and mass spectrometry were used to identify differentially expressed proteins. After proteomic analysis, we detected 405 and 371 protein spots within a pH range of 3-10 from sham-treated and contused brain cortex, respectively. Eighty protein spots were differentially expressed in the two groups and 20 of these proteins were identified. This study validated the established biomarkers of TBI and identified potential biomarkers that could be examined in future work.

Objective: To identify the early changes of serum neuroglobin and Nogo-A concentrations and the relations to traumatic brain injury (TBI) severity and prognosis.Methods: Serum samples were obtained and analyzed from 34 patients with TBI within the first 96h after injury. Comparative analysis combined with Glasgow Coma Scale (GCS) scores and the 6-month prognosis of these patients was performed.Results: Significant correlations were found between peak serum neuroglobin and Nogo-A concentrations and a patient's GCS score on admission (p<0.001). The mean peak serum neuroglobin and Nogo-A concentrations were both significantly higher in patients with an unfavorable outcome at 6 months after injury (p<0.05).Conclusions: Serum neuroglobin and Nogo-A levels could be suggested as biomarkers for predicting TBI severity and prognosis.

This meta-analysis examined whether early decompressive craniectomy (DC) can improve control of intracranial pressure (ICP) and mortality in patients with traumatic brain injury (TBI).Medline, Cochrane, EMBASE, and Google Scholar databases were searched until May 14, 2015, using the following terms: traumatic brain injury, refractory intracranial hypertension, high intracranial pressure, craniectomy, standard care, and medical management. Randomized controlled trials in which patients with TBI received DC and non-DC medical treatments were included.Of the 84 articles identified, 8 studies were selected for review, with 3 randomized controlled trials s having a total of 256 patients (123 DCs, 133 non-DCs) included in the meta-analysis. Patients receiving DC had a significantly greater reduction of ICP and shorter hospital stay. They also seemed to have lower odds of death than patients receiving only medical management, but the P value did not reach significance (pooled odds ratio 0.531, 95% confidence interval 0.209-1.350, Z=1.95, P=0.183) with respect to the effect on overall mortality; a separate analysis of 3 retrospective studies yielded a similar result.Whereas DC might effectively reduce ICP and shorten hospital stay in patients with TBI, its effect in decreasing mortality has not reached statistical significance.

XRCC3 has an important function in the DNA double-strand break, and XRCC3 C18607T polymorphism is a common polymorphism at exon 7 of the XRCC3 gene. Published data on the association between XRCC3 C18607T polymorphism and glioma risk were inconclusive. Electronic databases of PubMed, and Embase were searched for studies assessing the association between XRCC3 C18607T polymorphism and glioma risk. Pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated to estimate the association. Ten studies with five studies from Caucasians and five studies from Asians were included, including 9,369 subjects. Meta-analysis of total included studies showed that XRCC3 C18607T polymorphism was associated with increased risk of glioma (T vs. C: OR = 1.14, 95 % CI 1.02–1.28, P = 0.02; TT vs. CC: OR = 1.37, 95 % CI 1.03–1.83, P = 0.03; TT vs. CC/CT: OR = 1.31, 95 % CI 1.00–1.71, P = 0.05; TT/CT vs. CC: OR = 1.12, 95 % CI 1.02–1.22, P = 0.02). Meta-analysis of the five studies from Asians showed that XRCC3 C18607T polymorphism was associated with increased risk of glioma (T vs. C: OR = 1.22, 95% CI 1.09–1.36, P < 0.01; TT vs. CC: OR = 1.89, 95 % CI 1.38–2.57, P < 0.01; TT vs. CC/CT: OR = 1.78, 95 % CI 1.31–2.40, P < 0.01; TT/CT vs. CC: OR = 1.19, 95 % CI 1.04–1.36, P = 0.01). Meta-analysis of the five studies from Caucasians didn’t find the association. In conclusion, the finding from the meta-analysis provides strong evidence for the association between XRCC3 C18607T polymorphism and glioma risk.

Background/Aims: Aggregation of insoluble α-synuclein to form Lewy bodies (LBs) may contribute to the selective loss of midbrain dopaminergic neurons in Parkinson disease (PD). Lack of robust animal models has impeded elucidation of the molecular mechanisms of LB formation and other critical aspects of PD pathogenesis. Methods: We established a mouse model with targeted deletion of the plasminogen-binding protein tetranectin (TN) gene (TN-/-) and measured the behavioral and histopathological features of PD. Results: Aged (15-to 20-month-old) TN-/- mice displayed motor deficits resembling PD symptoms, including limb rigidity and both slower ambulation (bradykinesia) and reduced rearing activity in the open field. In addition, these mice exhibited more numerous α-synuclein-positive LB-like inclusions within the substantia nigra pars compacta (SNc) and reduced numbers of SNc dopaminergic neurons than age-matched wild type (WT) mice. These pathological changes were also accompanied by loss of dopamine terminals in the dorsal striatum. Conclusion: The TN-/- mouse exhibits several key features of PD and so may be a valuable model for studying LB formation and testing candidate neuroprotective therapies for PD and other synucleinopathies.

Aims: To investigate alterations in protein expression associated with deep brain stimulation (DBS) in an attempt to elucidate possible mechanisms of action. Methods: Cerebrospinal fluid (CSF), obtained from six Parkinson's disease (PD) patients (pre- and post-DBS) and from six normal healthy controls, was studied for differentially expressed proteins. 2-D DIGE, in combination with MALDI-TOF and TOF-TOF Mass Spectrometry (MS) or ESI-MS, was used to identify the changed proteins (3 PD patients and 3 controls). Selected proteins were further studied using western blotting (6 PD patients and 6 controls). Results: Twenty-one proteins were identified after MS and protein database interrogation. Apart from apolipoprotein A-I (apoA-I), the expression levels of complement C4 (C4), IgA, tetranectin, and extracellular superoxide dismutase (EC-SOD), detected by western blotting, correlated well with the 2-D DIGE results. In the follow-up period, the expression levels of C4, apoA-I and IgA were stable whereas EC-SOD and tetranectin were significantly elevated. In addition, when DBS was ceased in one patient due to a suicide attempt, the levels of EC-SOD and tetranectin significantly decreased. Conclusion: Our preliminary results suggest that variations in the expression levels of EC-SOD and tetranectin in CSF is related to DBS.

Objective To investigate the value of 3.0T magnetic resonance imaging(MRI) in diagnosis of severe traumatic brain injury and outcome prediction.Methods Thirty-eight patients with severe traumatic brain injury were evaluated with MRI 4 to 6 weeks after injury,the lesion volumes in T1 and T2 weighted imaging and fluid attenuated inversion recovery(FLAIR) images were quantified and compared with simultaneous CT findings.The diffuse axonal injury(DAI) scores were recorded,and correlation analysis was performed with Glasgow coma scale(GCS) on admission and Glasgow outcome scale(GOS) 6 months after injury.Results MRI demonstrated more lesions than CT,especially for the corpus callosum and brain stem lesions.There were significant differences in DAI scores and lesion volumes in T1 and T2 weighted imaging and FLAIR images between different outcome groups(P0.05).DAI score had strongest correlation with GOS 6 months after injury(r=-0.854,P0.05),and the lesion volume detected by MRI was also negatively correlated with the outcome(P0.05).Conclusion 3.0T MRI is superior to CT in detection of intraparenchymal injury,especially for deep lesions.A quantitative study of the lesion volume and location demonstrated by MRI may play a role in outcome prediction.

Objective To explore the pathogenesis,clinicopathological features and key points for diagnosis and treatment of chronic expanding intracerebral hematoma(CEIH).Methods Clinicopathological and imaging data of 9 patients with CEIH diagnosed by operation were analyzed retrospectively.The patients underwent craniotomy and lesion resection under microscope.Results Total lesion resection was achieved in 9 patients under microscope.The pathological results revealed arteriovenous malformation in 1 patient,hemangioma in 1 and no vascular abnormality was seen in other patients.The symptoms completely disappeared postoperation in 6 patients and relieved in 3.No patient recurred during a follow-up period of 3 months to 1 year.Conclusions The intracerebral shadow similar to tumor hemorrhage in imaging with recurrent attacks and chronic expanding should be considered CEIH,and total resection is the first choice of treatment for CEIH.

Recent studies have suggested that endogenous angiogenesis inhibitor endostatin/collagen XVIII might play an important role in the secondary brain injury following traumatic brain injury (TBI). In this study, we measured endostatin/collagen XVIII concentrations serially for 1 week after hospitalization by using the enzyme-linked immunosorbent assay method in the cerebrospinal fluid (CSF) of 30 patients with TBI and a Glasgow Coma Scale (GCS) score of 8 or less on admission. There was a significant trend toward increased CSF levels of endostatin after TBI versus control from 72 h after injury. In patients with GCS score of 3–5, CSF endostatin concentration was substantially higher at 72 h after injury than that in patients with GCS score of 6–8 (P<0.05) and peaked rapidly at day 5 after injury, but decreased thereafter. The CSF endostatin concentration in 12 patients with an unfavorable outcome was significantly higher than that in 18 patients with a favorable outcome at day 5 (P=0.043) and day 7 (P=0.005) after trauma. Receiver operating characteristic curve analysis suggested a reliable operating point for the 7-day CSF endostatin concentration predicting poor prognosis to be 67.29 pg/mL. Our preliminary findings provide new evidence that endostatin/collagen XVIII concentration in the CSF increases substantially in patients with sTBI. Its dynamic change may have some clinical significance on the judgment of brain injury severity and the assessment of prognosis. This trial is registered with the ClinicalTrials.gov Identifier: NCT01846546.