Cellular Localization and Distribution of TGF-ß1, GDNF and PDGF-BB in the Adult Primate Central Nervous System.

The available data on the localization of transforming growth factor beta1 (TGF-ß1), glial cell line-derived neurotrophic factor (GDNF), and platelet-derived growth factor-BB (PDGF-BB) in the adult primate and human central nervous system (CNS) are limited and lack comprehensive and systematic information. This study aimed to investigate the cellular localization and distribution of TGF-ß1, GDNF, and PDGF-BB in the CNS of adult rhesus macaque (Macaca mulatta). Seven adult rhesus macaques were included in the study. The protein levels of TGF-ß1, PDGF-BB, and GDNF in the cerebral cortex, cerebellum, hippocampus, and spinal cord were analyzed by western blotting. The expression and location of TGF-ß1, PDGF-BB, and GDNF in the brain and spinal cord was examined by immunohistochemistry and immunofluorescence staining, respectively. The mRNA expression of TGF-ß1, PDGF-BB, and GDNF was detected by in situ hybridization. The molecular weight of TGF-ß1, PDGF-BB, and GDNF in the homogenate of spinal cord was 25 KDa, 30 KDa, and 34 KDa, respectively. Immunolabeling revealed GDNF was ubiquitously distributed in the cerebral cortex, hippocampal formation, basal nuclei, thalamus, hypothalamus, brainstem, cerebellum, and spinal cord. TGF-ß1 was least distributed and found only in the medulla oblongata and spinal cord, and PDGF-BB expression was also limited and present only in the brainstem and spinal cord. Besides, TGF-ß1, PDGF-BB, and GDNF were localized in the astrocytes and microglia of spinal cord and hippocampus, and their expression was mainly found in the cytoplasm and primary dendrites. The mRNA of TGF-ß1, PDGF-BB, and GDNF was localized to neuronal subpopulations in the spinal cord and cerebellum. These findings suggest that TGF-ß1, GDNF and PDGF-BB may be associated with neuronal survival, neural regeneration and functional recovery in the CNS of adult rhesus macaques, providing the potential insights into the development or refinement of therapies based on these factors.

Portable 3D-Head Computed Tomography (CT) Navigation-Guided Key-Hole Microsurgery for Spontaneous Hypertensive Hemorrhages.

BACKGROUND This case series study evaluated the outcome and effect of portable 3D-head computed tomography (CT, MCT-I, 16 rows mobile CT made in China) navigation-guided key-hole microsurgery for supratentorial hypertensive hematomas. MATERIAL AND METHODS Thirty-five consecutive unconscious patients with a significant volume of hypertensive intracranial hemorrhages (HICH) were treated with 3D image-guided key-hole microsurgery, and the clinical features were summarized. Preoperative and postoperative hematoma volumes and reduction in midline shifts were calculated and recorded. The preoperative and postoperative (initial, discharge, and 180th day after stroke onset) neurological status was assessed by Glasgow Outcome Scale (GOS), Glasgow Coma Scale (GCS), and modified Rankin Scale (mRS) score, respectively. RESULTS The range of hematoma volumes of surgical patients was 24-99 ml (median, 50 ml). The median time of CT scan (from the time of the request to navigation finish) was 11 min. Total and near-total (>90%) hematoma evacuation was achieved in 96.9% cases. Compared with the initial state of neurological assessment, there was a significant improvement in MRS and GCS at discharge (P<0.001). After 6 months, 57.1% of patients had achieved functional recovery (GOS 4-5) and 2 patients had died. CONCLUSIONS As a minimally invasive technique, image-guided transcortical sulci or transsylvian approach is highly effective for immediate and complete hematoma evacuation.

Effect evaluation of methylprednisolone plus mitochondrial division inhibitor-1 on spinal cord injury rats.

PURPOSE: To investigate the combination effect of methylprednisolone (MP) and mitochondrial division inhibitor-1 (Mdivi-1) on the neurological function recovery of rat spinal cord injury (SCI) model. METHODS: The weight-drop method was used to establish the rat SCI model; then, rats were randomized into sham group, SCI group, MP group, Mdivi-1 group and MP+Mdivi-1 group. Motor function scores were quantified to evaluate locomotor ability; HE staining was used to assess spinal cord histopathology; tissue water content, oxidative stress, tissue mitochondrial function, neurons apoptosis, and apoptosis-related protein expression were detected. RESULTS: From the third day after SCI, BBB score of the MP+Mdivi-1 group was obviously higher than the other experimental groups (p < 0.05). Compared with the SCI group, tissue water content of the Mdivi-1 group and MP+Mdivi-1 group reduced obviously (p < 0.05), mitochondrial membrane potential (MMP) level and ATP content in the Mdivi-1 group and MP+Mdivi-1 group were both higher (p < 0.05). Meanwhile, three kinds of treatment all reduced apoptosis significantly, while MP plus Mdivi-1 exhibited the best inhibition effect on apoptosis (p < 0.05). The expression levels of Drp1, cytochrome c, and caspase-3 were all upregulated obviously; Mdivi-1 could inhibit Drp1 upregulation induced by SCI; for the upregulation of cytochrome c and caspase-3, the inhibition effect of Mdivi-1 approached MP. When MP combined with Mdivi-1, there was the best inhibition effect. CONCLUSIONS: MP combined with Mdivi-1 may produce better neurological function recovery, through improving functional status of mitochondria and inhibiting lipid peroxidation in damaged tissue of SCI rats, and thus alleviating apoptosis.

Anti-inflammatory Effect of Mesenchymal Stromal Cell Transplantation and Quercetin Treatment in a Rat Model of Experimental Cerebral Ischemia.

Here, we have investigated the synergistic effect of quercetin administration and transplantation of human umbilical cord mesenchymal stromal cells (HUMSCs) following middle cerebral artery occlusion in rat. Combining quercetin treatment with delayed transplantation of HUMSCs after local cerebral ischemia significantly (i) improved neurological functional recovery; (ii) reduced proinflammatory cytokines (interleukin(IL)-1ß and IL-6), increased anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor-ß1), and reduced ED-1 positive areas; (iii) inhibited cell apoptosis (caspase-3 expression); and (iv) improved the survival rate of HUMSCs in the injury site. Altogether, our results demonstrate that combined HUMSC transplantation and quercetin treatment is a potential strategy for reducing secondary damage and promoting functional recovery following cerebral ischemia.

Local Injection of Lenti-BDNF at the Lesion Site Promotes M2 Macrophage Polarization and Inhibits Inflammatory Response After Spinal Cord Injury in Mice.

There is much evidence to suggest that brain-derived neurotrophic factor (BDNF) is a prominent candidate in promoting neuroprotection, axonal regeneration, and synaptic plasticity following spinal cord injury (SCI). Although some evidence indicates that BDNF has potent anti-oxidative effects and may be involved in the regulation of the immune response, the effects of BDNF in the inflammatory response during the course of secondary damage after SCI is still unclear. The present study was designed to investigate the effects of BDNF with a special focus on their effect on macrophage polarization after SCI. Adult C57 mice underwent T10 spinal cord clip compression injury and received lenti-BDNF vector injections at the epicenter of the lesion site. Four days later, total BDNF levels were greatly increased in animals that received lenti-BDNF injections. Confocal imaging showed that more than 80 % of the lenti-virus infected cells were CD11b-positive macrophages. In addition, the expression of arginase-1 and CD206 (associated with M2 macrophage phenotype) significantly increased in the animals that received lenti-BDNF injections compared with those that received lenti-EGFP injections. On the contrary, the expression of CD16/32 and inducible nitric oxide synthase (M1 phenotype marker) was down-regulated as demonstrated using flow cytometry and immunohistochemistry. Furthermore, the production of interleukin 1ß and tumor necrosis factor alpha was significantly reduced whereas the levels of interleukin 10 and interleukin 13 were elevated in subjects that received lenti-BDNF vector injections. The time course of functional recovery revealed that gradual recovery was observed in the subacute phase in lenti-BDNF group, little improvement was observed in lenti-EGFP group. At the axonal level, significant retraction of the CST axons were observed in lenti-EGFP injected animals relative to lenti-BDNF group by biotinylated dextran amine tracing. In addition, compared to lenti-BDNF group markedly demyelination was observed in the lenti-EGFP group using luxol fast blue staining. In conclusion, we found that BDNF could promote the shift of M1 to M2 phenotype and ameliorate the inflammatory microenvironment. Furthermore, the roles of BDNF in immunity modulation may enhance neuroprotective effects and partially contribute to the locomotor functional recovery after SCI.

Transsylvian-transinsular approach to large lateral thalamus hemorrhages.

Here, we aimed to evaluate the experience of transsylvian-transinsular microsurgical approach (TTH) to the huge lateral thalamic hemorrhages (THs). A total of 37 patients with huge lateral TH (hematoma volumes between 30 and 90 cm) who underwent surgical treatment through middle or distal TTH at the Bayi Brain Hospital from January 2007 to May 2012 were included in this series. By using TTH, near-complete (99%) evacuation was achieved in 29 patients (78.4%). Glasgow Coma Scale (GOS) scores were significantly improved at discharge compared with admission scores (P < 0.001). The overall survival rate at 3 months was 81.08% (30/37), including 51.35% (19/37) with good function (GOS, 4-5), 13.51% (5/37) with disability (GOS, 3), and 16.22% (6/37) in a vegetative state (GOS, 2). The mortality rate (GOS, 1) was 18.92% (7/37). Our series showed that, according to the extension direction of hematomas, to select middle or distal TTH is effective and safe for TH.

Hematoporphyrin derivative-mediated photodynamic techniques for the diagnosis and treatment of chordoma.

BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.

Dopamine receptor 1 modulates the discharge activities of inspiratory and biphasic expiratory neurons via cAMP-dependent pathways.

Dopamine receptor 1 (D(1)R) plays an essential role in regulating respiratory activity in mammals, however, little is known about how this receptor acts to modulate the basic respiratory rhythmogenesis. Here, by simultaneously recording the discharge activities of biphasic expiratory (biphasic E) neurons/inspiratory (I) neurons and the XII nerve rootlets from brainstem slices, we found that the application of D(1)R agonist cis-(±)-1-(aminomethyl)-3,4-dihydro-3-phenyl-1H-2-benzopyran-5,6-diolhydrochloride (A68930, 5 µM), or forskolin, an intracellular cAMP-increasing agent, substantially decreased respiratory cycle and expiratory time of both types of neurons, and elevated the integral amplitude and frequency of XII nerve rootlets discharge. These changes were reversed by subsequent application of their antagonists SCH-23390 and Rp-Adenosine 3',5'-cyclic monophosphorothioate triethylammonium salt hydrate (Rp-cAMPS), respectively. Importantly, after pretreatment with Rp-cAMPS, the effects of A68930 in both types of neurons were blocked, suggestive of a cAMP-dependent action of A68930. Thus, the current study indicates that D(1)R may modulate basic breathing rhythmogenesis via cAMP-dependent mechanisms.

Comparison of the neural differentiation potential of human mesenchymal stem cells from amniotic fluid and adult bone marrow.

Human mesenchymal stem cells (MSCs) are considered a promising tool for cell-based therapies of nervous system diseases. Bone marrow (BM) has been the traditional source of MSCs (BM-MSCs). However, there are some limitations for their clinical use, such as the decline in cell number and differentiation potential with age. Recently, amniotic fluid (AF)-derived MSCs (AF-MSCs) have been shown to express embryonic and adult stem cell markers, and can differentiate into cells of all three germ layers. In this study, we isolated AF-MSCs from second-trimester AF by limiting dilution and compared their proliferative capacity, multipotency, neural differentiation ability, and secretion of neurotrophins to those of BM-MSCs. AF-MSCs showed a higher proliferative capacity and more rapidly formed and expanded neurospheres compared to those of BM-MSCs. Both immunocytochemical and quantitative real-time PCR analyses demonstrated that AF-MSCs showed higher expression of neural stemness markers than those of BM-MSCs following neural stem cell (NSC) differentiation. Furthermore, the levels of brain-derived growth factor and nerve growth factor secreted by AF-MSCs in the culture medium were higher than those of BM-MSCs. In addition, AF-MSCs maintained a normal karyotype in long-term cultures after NSC differentiation and were not tumorigenic in vivo. Our findings suggest that AF-MSCs are a promising and safe alternative to BM-MSCs for therapy of nervous system diseases.

Neural stem-like cells derived from human amnion tissue are effective in treating traumatic brain injury in rat.

Although human amnion derived mesenchymal stem cells (AMSC) are a promising source of stem cells, their therapeutic potential for traumatic brain injury (TBI) has not been widely investigated. In this study, we evaluated the therapeutic potential of AMSC using a rat TBI model. AMSC were isolated from human amniotic membrane and characterized by flow cytometry. After induction, AMSC differentiated in vitro into neural stem-like cells (AM-NSC) that expressed higher levels of the neural stem cell markers, nestin, sox2 and musashi, in comparison to undifferentiated AMSC. Interestingly, the neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), glial cell derived neurotrophic factor (GDNF) and ciliary neurotrophic factor (CNTF) were markedly upregulated after neural stem cell induction. Following transplantation in a rat TBI model, significant improvements in neurological function, brain tissue morphology, and higher levels of BDNF, NGF, NT-3, GDNF and CNTF, were observed in the AM-NSC group compared with the AMSC and Matrigel groups. However, few grafted cells survived with minimal differentiation into neural-like cells. Together, our results suggest that transplantation of AM-NSC promotes functional rehabilitation of rats with TBI, with enhanced expression of neurotrophic factors a likely mechanistic pathway.

Distal transsylvian-traninsular approach for the putaminal hypertensive hemorrhages: surgical experience and technical note.

BACKGROUND: Up to now, no systemic studies about the surgical approaches and microsurgical techniques of distal transsylvian-transinsular approach to putaminal hypertensive intracranial hemorrhages (PHHs) were reported. METHODS: A retrospective analysis was performed on 68 consecutive patients with PHH who underwent surgical treatment at the Department of the affiliated Bayi Brain Hospital, the Military General Hospital of Beijing PLA, from May 2009 to December 2011. RESULTS: By using transsylvian-transinsular approach, near-complete (>90%) evacuation was achieved in 51 cases (75%). Glasgow Coma Scale scores were significantly improved at discharge compared with admission scores (P < 0.001). The overall survival rate at 6 months was 95.6% (65/68), including 60.3% (41/68) with good function (Glasgow Outcome Scale [GOS] score, 4-5), 19.1% (13/68) with disability (GOS score, 3), and 16.2% (11/68) in a vegetative state (GOS score, 2). The mortality rate (GOS score, 1) was 4.4% (3/68). CONCLUSIONS: Transsylvian-transinsular approach is effective and minimally invasive for PHH. The opening of sylvian fissure toward the pars opercularis behind the level of anterior ascending rami could provide a more suitable angle to hematoma and the ability to treat the responsible vessels.

Neural differentiation ability of mesenchymal stromal cells from bone marrow and adipose tissue: a comparative study.

BACKGROUND AIMS: The characteristics, such as morphologic and phenotypic characteristics and neural transdifferentiation ability, of mesenchymal stromal cells (MSC) derived from different origins have yet to be reported for cases isolated from the same individual. METHODS: The proliferation capacity, secretion ability of neurotrophins (NT) and neural differentiation ability in rat MSC isolated from bone marrow (BMSC) and adipose tissue (ADSC) were compared from the same animal. RESULTS: The ADSC had a significantly higher proliferation capacity than BMSC according to cell cycle and cumulative population doubling analyses. The proportion of cells expressing neural markers was greater in differentiated ADSC than in differentiated BMSC. Furthermore, the single neurosphere derived from ADSC showed stronger expansion and differentiation abilities than that derived from BMSC. The findings from Western blot lent further support to the immunocytochemical data. The mRNA and protein levels of nerve growth factor (NGF) and brain-derived growth factor (BDNF) expressed in ADSC were significantly higher than those in BMSC at different stages before and following induction. CONCLUSIONS: Our study suggests that the proliferation ability of ADSC is superior to that of BMSC. Furthermore, differentiated ADSC expressed higher percentages of neural markers. As one possible alternative source of BMSC, ADSC may have wide potential for treating central nervous system (CNS) diseases.

Expression of cytokines in rat brain with focal cerebral ischemia after grafting with bone marrow stromal cells and endothelial progenitor cells.

BACKGROUND AIMS: This study aimed to observe nine factors expressed in rat ischemic brain after transplantation of bone marrow stromal cells (BMSC) and/or endothelial progenitor cells (EPC). These factors were vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF-l), transforming growth factor-ß (TGF-ß), platelet-derived growth factor-BB (PDGF-BB), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF). METHODS: Adult Wistar rats were divided randomly into four groups: a vehicle group, BMSC group, EPC group and BMSC combined with EPC group. The rats were subjected to middle cerebral artery occlusion (MCAO) then implanted intravenously with 3 × 10(6) BMSC, EPC, BMSC/EPC or phosphate-buffered saline (PBS) 24 h after MCAO. Neurologic functional deficits were measured on days 1, 7, 14, 28 after transplantation. On day 7 after transplantation, quantitative reverse transcription (qRT)-polymerase chain reaction (PCR) and Western blot were employed to detect the expression of VEGF, SDF-1, bFGF, IGF-l, TGF-ß, PDGF-BB, BDNF, GDNF and NGF. RESULTS: The neurologic evaluation found that the neurologic severity scores were no different between the four groups on day 1, and the scores of rats in the BMSC/EPC group were significantly lower than those of rats in the other groups on days 7, 14 and 28 after transplantation. The expressions of bFGF, VEGF and BNDF were significantly higher in the BMSC/EPC group compared with the other groups. CONCLUSIONS: The intravenous transplantation of BMSC combined with EPC could promote the functional rehabilitation of rats with focal cerebral ischemia, and the mechanism may be related to the enhanced expression of factors.

In vitro and in vivo magnetic resonance tracking of Sinerem-labeled human umbilical mesenchymal stromal cell-derived Schwann cells.

Tracking of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles-labeled embryonic stem cells, neural stem cells, or adult mesenchymal stem cells in vitro and in vivo by using magnetic resonance (MR) imaging have been reported. However, whether the transdifferentiated cells can be effectively labeled by USPIO has not yet been investigated. The requirement for nerve donor material evokes additional morbidity and inability to generate a sufficiently large number of cells in a short time to hamper the clinic application of Schwann cells (SCs) transplantation. These limitations may be avoided if SCs can be generated from clinically accessible sources, such as bone marrow and umbilical cord. However, a reliable means of inducing the selective differentiation of human mesenchymal stromal cells isolated from the umbilical cord (HUMSCs) into SCs in vitro has not yet been established. In this study, we induce HUMSCs into Schwann-like cells in terms of morphology, phenotype, and function by an improved protocol basing on our previous studies. Furthermore, HUMSCs-derived SCs are labeled efficiently in vitro with ultrasmall superparamagnetic iron oxide contrast agent (USPIO) Sinerem and poly-L-lysine (PLL) without affecting morphology, cell cycle, proliferation, and differentiation ability of the labeled cells between the concentration of 200 to 800 µg/ml. Importantly, when grafted into the intact cerebral cortex and striatum, the survival and migration of these Sinerem-labeled cells were observed using MRI. Our study suggest the effective concentration field for Sinerem use in tracking transdifferentiated HUMSCs, and Sinerem labeling transdifferentiated HUMSCs is feasible, efficient, and safe for MRI tracing following grafting into nervous system.

Comparison of transdifferentiated and untransdifferentiated human umbilical mesenchymal stem cells in rats after traumatic brain injury.

Transdifferentiated and untransdifferentiated mesenchymal stem cells (MSCs) have shown therapeutic benefits in central nervous system (CNS) injury. However, it is unclear which would be more appropriate for transplantation. To address this question, we transplanted untransdifferentiated human umbilical mesenchymal stem cells (HUMSCs) and transdifferentiated HUMSCs (HUMSC-derived neurospheres, HUMSC-NSs) into a rat model of traumatic brain injury. Cognitive function, cell survival and differentiation, brain tissue morphology and neurotrophin expression were compared between groups. Significant improvements in cognitive function and brain tissue morphology were seen in the HUMSCs group compared with HUMSC-NSs group, which was accompanied by increased neurotrophin expression. Moreover, only few grafted cells survived in both the HUMSCs and HUMSC-NSs groups, with very few of the cells differentiating into neural-like cells. These findings indicate that HUMSCs are more appropriate for transplantation and their therapeutic benefits may be associated with neuroprotection rather than cell replacement.

Human Wharton's jelly cells can be induced to differentiate into growth factor-secreting oligodendrocyte progenitor-like cells.

Human Wharton's jelly-derived mesenchymal stromal cells (hWJ-MSCs) are capable of differentiating into neural and astroglia-like cell types. However, a reliable means of inducing the selective differentiation of hWJ-MSCs into oligodendrocyte progenitor cells (OPCs) in vitro has not yet been established. In this study, the OPC-like differentiation of hWJ-MSCs was characterized using and immunoblotting. The hWJ-MSC-derived OPC-like cells were able to secrete nerve growth factors and promote neurite outgrowth in vitro. These results show that hWJ-MSCs can be induced to differentiate into cells with the morphologic, phenotypic and functional characteristics of OPC-like cells.

Microsurgery for Vestibular Schwannoma via Retrosigmoid Transmeatal Approach with Intraoperative Monitoring Techniques.

BACKGROUND: Functional preservation of cranial nerves remains an issue in surgical treatment of vestibular schwannoma. AIMS: To explore the functional outcomes of vestibular schwannoma removed by microsurgery via a retrosigmoid transmeatal approach with intraoperative monitoring techniques. STUDY DESIGN: A retrospective cross-sectional study was conducted on a group of patients with vestibular schwannoma operated by microsurgery. METHODS: The outcomes, including the extent of tumor removal, the anatomic positions of the facial nerve, and postoperative Karnofsky performance status score, facial nerve function, and hearing function were reviewed and were statistically compared among tumor sizes (small, medium, and giant) and intraoperative monitoring types [electrophysiological monitoring only (E), electrophysiological monitoring + intraoperative imaging examination (E+I), and electrophysiological monitoring + neuronavigation (E+N)]. RESULTS: A total of 436 patients with VS received microsurgery. The position of the facial nerve was anterior in 85.5% of cases with small vestibular schwannoma. Other position patterns, especially anterior- superior and anterior-inferior, increased in tumors > 2.0 cm. Total resections were performed in all patients with small vestibular schwannoma. A total of 98.1% and 84.8% of patients with medium and giant vestibular schwannoma, respectively, had total resections. More than 90% of patients in all of the 3 monitoring groups had total resections. More than 80% of patients had excellent Karnofsky performance status score regardless of tumor size and monitoring type. After surgery, 100%, 84.4%, and 59.8% of patients with small-, medium-, and giant-sized vestibular schwannoma, respectively, had good facial nerve function. More than 70% of patients in all of the 3 monitoring groups had good facial nerve function postoperatively. The hearing preservation rate was 26.7% and 7.7% in small- and medium-sized vestibular schwannoma, respectively, and was 21.6% and 27.3% in the E group and the E+N group, respectively. The statistical analyses showed that tumor size was significantly associated with the extent of tumor resection, facial nerve localization, complications, postoperative Karnofsky performance status score, facial nerve function, and hearing function (all P ≤ .001). Monitoring type was significantly associated with the extent of resection (P ≤ .001). Additionally, patients in the E+N group had higher total resection rates than those in the E group (P ≤ .001). No cerebrospinal fluid leakage and surgery-related death occurred. CONCLUSION: In vestibular schwannoma microsurgery, tumor size is an important parameter that affects the localization of the facial nerve, the extent of resection, postoperative outcomes and complications. Intraoperative electrophysiological techniques combined with neuronavigation may be helpful to improve the extent of resection.

White matter demyelination predates axonal injury after ischemic stroke in cynomolgus monkeys.

Unraveling the pathology of stroke is a prerequisite for designing therapeutic strategies. It was reported that myelin injury exceeded axonal loss in the peri-infarct region of rodent white matter stroke. An in-depth investigation of the post-stroke white matter damage in higher-order species might innovate stroke intervention. In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO, while a progressive loss of myelin and axons was observed after one month. Gliosis, microglia activation, and leukocyte infiltration were identified in the lesions. These results demonstrate that demyelination predates axonal injury in non-human primate ischemic stroke, which provides a time window for stroke intervention focusing on prevention of progressive axonal loss through myelin regeneration.

The microsurgical treatment for primary hypertensive brainstem hemorrhage: Experience with 52 patients.

OBJECTIVE: This study aims to investigate the effect of minimal invasive microsurgery in treating primary hypertensive brainstem hemorrhage (PHBH). METHODS: 52 patients of PHBH (≥3.5 ml) who have taken the minimal invasive microsurgery with neuronavigation guidance were included between Jan. 2011 and Dec. 2018. The volume/location/type of hematoma, preoperative Glasgow Coma Scale (GCS), postoperative Glasgow Outcome Scale (GOS) and hemorrhagic dilatation of the fourth ventricle were analyzed during the follow-up period ranged from 3 to 57 months. RESULTS: Among all the patients, 18 achieved complete hematoma evacuation (≥95%), 31 achieved subtotal evacuation (≥90%), 3 achieved premodinantly evacuation (>75%). No rebleeding during or after surgery within 24 h were found. 45 patients survived after 3 months, the mean preoperative hematoma volume decreased from 7.1 ± 2.6 ml-0.9 ml (p < 0.05), 19 patients got GOS Grade V/Ⅳ. It is shown the volume less than 10 ml always led to better outcome while massive and bilateral hematoma were related with poor prognosis. CONCLUSION: The microsurgical hematoma evacuation under neuronavigation assistance is a rapid, effective, and safe technique for the removal of PHBH, especially for the volume less than 10 ml.

Glial cells are involved in the exciting effects of doxapram on brainstem slices in vitro.

This study tested whether the glial cells are involved in the exciting effects of doxapram on brainstem slice in vitro. Experiments were performed in brainstem slice preparations from neonatal rats. The medial area of nucleus retrofacialis (mNRF) and the hypoglossal nerve (XII nerve) were contained in the preparations. The slices were perfused with modified Kreb's solution (MKS), and the rhythmical respiratory discharge activity (RRDA) was simultaneously recorded from the XII nerve by using suction electrodes, including the discharge time course of inspiratory (Ti), expiratory (Te), respiratory cycle (RC), and integrity amplitude of inspiratory discharge (IA). After applying of doxapram (5 microM) to the MKS for 10 min, Ti and IA increased significantly (85.0 +/- 25.0%, 13.2 +/- 2.5%, respectively, P < 0.05), the Te and the RC decreased significantly (19.0 +/- 1.4%, 12.8 +/- 1.4%, respectively, P < 0.05) when compared with control group. When the methionine sulfoximine (MS, 10 microM), a blockage of glutamine synthetase, was applied, all the exciting effects of doxapram on RRDA were reversed. After the glutamine (20 microM) was applied to the MKS for 10 min, the exciting effects were revealed again. Our results suggest that the normal metabolism of glial cells takes a key role in the modification of the RRDA in the slices. In conclusion, glial cells are involved in the exciting effects of doxapram on brainstem slice in vitro.