Middle third falcine meningiomas-surgical nuances for cortical venous preservation.

PURPOSE: To improve postoperative outcome in middle third falcine meningiomas by cortical venous preservation. BACKGROUND: Falcine meningiomas arise from the falx and do not involve the superior sagittal sinus (SSS). Their complete resection is often associated with the risk of venous infarction in the eloquent cortex due to overlying superficial cortical veins on the tumors. METHOD: We report one case of middle third falcine meningioma, where we used the posterior interhemispheric corridor for tumor approach. CONCLUSION: Use of the posterior interhemispheric approach, carefully raised bone flap, along with sharp dissection and vein reinforcement using fibrin glue can help to preserve the cortical veins while resecting the falcine meningiomas.

Lentivirus- or AAV-mediated gene therapy interventions in ischemic stroke: A systematic review of preclinical in vivo studies.

Due to the limited therapeutic options after ischemic stroke, gene therapy has emerged as a promising choice, especially with recent advances in viral vector delivery systems. Therefore, we aimed to provide the current state of the art of lentivirus (LV) and adeno-associated virus (AAV) mediated gene interventions in preclinical ischemic stroke models. A systematic analysis including qualitative and quantitative syntheses of studies published until December 2020 was performed. Most of the 87 selected publications used adult male rodents and the preferred stroke model was transient middle cerebral artery occlusion. LV and AAV vectors were equally used for transgene delivery, however loads of AAVs were higher than LVs. Serotypes having broad cell tropism, the use of constitutive promoters, and virus delivery before the stroke induction via stereotaxic injection in the cortex and striatum were preferred in the analyzed studies. The meta-analysis based on infarct volume as the primary outcome confirmed the efficacy of the preclinical interventions. The quality assessment exposed publication bias and setbacks in regard to risks of bias and study relevance. The translational potential could increase by using specific cell targeting, post-stroke interventions, non-invasive systematic delivery, and use of large animals.

Blood supply to the corticospinal tract: A pictorial review with application to cranial surgery and stroke.

The corticospinal tract (CST) is the main neural pathway responsible for conducting voluntary motor function in the central nervous system. The CST condenses into fiber bundles as it descends from the frontoparietal cortex, traveling down to terminate at the anterior horn of the spinal cord. The CST is at risk of injury from vascular insult from strokes and during neurosurgical procedures. The aim of this article is to identify and describe the vasculature associated with the CST from the cortex to the medulla. Dissection of cadaveric specimens was carried out in a manner, which exposed and preserved the fiber tracts of the CST, as well as the arterial systems that supply them. At the level of the motor cortex, the CST is supplied by terminal branches of the anterior cerebral artery and middle cerebral artery. The white matter tracts of the corona radiata and internal capsule are supplied by small perforators including the lenticulostriate arteries and branches of the anterior choroidal artery. In the brainstem, the CST is supplied by anterior perforating branches from the basilar and vertebral arteries. The caudal portions of the CST in the medulla are supplied by the anterior spinal artery, which branches from the vertebral arteries. The non-anastomotic nature of the vessel systems of the CST highlights the importance of their preservation during neurosurgical procedures. Anatomical knowledge of the CST is paramount to clinical diagnosis and treatment of heterogeneity of neurodegenerative, neuroinflammatory, cerebrovascular, and skull base tumors.

Orexin-A alleviates astrocytic apoptosis and inflammation via inhibiting OX1R-mediated NF-κB and MAPK signaling pathways in cerebral ischemia/reperfusion injury.

Orexin-A (OXA) is a neuropeptide with neuroprotective effect by reducing cerebral ischemia/reperfusion injury (CIRI). Inflammation and apoptosis mediated by astrocyte activation are the key pathological mechanisms for CIRI. We thus attempted to confirm neuroprotective effects of OXA on astrocytic inflammation and apoptosis in CIRI and clarify the relative mechanisms. A middle cerebral artery occlusion and reperfusion (MCAO/R) rat model and U251 glioma cells model subjected to oxygen glucose deprivation and reperfusion (OGD/R) were established, with or without OXA treatment. Neurological deficit score was determined, and cerebral infarct volume was evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Western Blot was used to detect the expressions of NF-κB p65, p-p65, p-ERK, p-p38, GFAP, OX1R, IL-1ß, TNF-α, IL-6, iNOS, Bcl-2, Bax, CytC, cleaved caspase-9 and cleaved caspase-3 in vivo and in vitro. Pro-inflammatory cytokines in cell supernatant IL-1ß, TNF-α and IL-6 were determined by ELISA. Hoechst 33342 staining was used to detect the apoptosis of astrocyte. Immunofluorescent staining was performed to assess the nuclear translocation of p65 and the expression of GFAP. The results showed that OXA significantly improved neurological deficit score and decreased the volume of infarct area in brain. OXA decreased inflammatory mediators, inhibited astrocyte activation and nuclear translocation of NF-κB and phosphorylation of NF-κB, MAPK/ERK and MAPK/p38. Besides, OXA suppressed apoptosis via upregulating the ratio of Bcl-2/Bax and downregulating cytochrome C, cleaved-caspase-9 and cleaved caspase-3. Overall, it was concluded that OXA exerts neuroprotective effect during CIRI through attenuating astrocytes apoptosis, astrocytes activation and pro-inflammatory cytokines production, by Inhibiting OX1R-mediated NF-κB, MAPK/ERK and MAPK/p38 signaling pathways. The progress in our study is helpful to elucidate the molecular mechanisms of OXA neuroprotection, which could lead to the development of new treatment strategies for ischemic stroke.

Transcriptomic Hallmarks of Ischemia-Reperfusion Injury.

Ischemia reperfusion injury (IRI) is associated with a broad array of life-threatening medical conditions including myocardial infarct, cerebral stroke, and organ transplant. Although the pathobiology and clinical manifestations of IRI are well reviewed by previous publications, IRI-related transcriptomic alterations are less studied. This study aimed to reveal a transcriptomic hallmark for IRI by using the RNA-sequencing data provided by several studies on non-human preclinical experimental models. In this regard, we focused on the transcriptional responses of IRI in an acute time-point up to 48 h. We compiled a list of highly reported genes in the current literature that are affected in the context of IRI. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses and found many of the up-regulated genes to be involved in cell survival, cell surface signaling, response to oxidative stress, and inflammatory response, while down-regulated genes were predominantly involved in ion transport. Furthermore, by GO analysis, we found that multiple inflammatory and stress response processes were affected after IRI. Tumor necrosis factor alpha (TNF) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways were also highlighted in the Kyoto Encyclopedia of Genes and Genomes enrichment analysis. In the last section, we discuss the treatment approaches and their efficacy for IRI by comparing RNA sequencing data from therapeutic interventions with the results of our cross-comparison of differentially expressed genes and pathways across IRI.

Simulation of angiogenesis in three dimensions: Application to cerebral cortex.

The vasculature is a dynamic structure, growing and regressing in response to embryonic development, growth, changing physiological demands, wound healing, tumor growth and other stimuli. At the microvascular level, network geometry is not predetermined, but emerges as a result of biological responses of each vessel to the stimuli that it receives. These responses may be summarized as angiogenesis, remodeling and pruning. Previous theoretical simulations have shown how two-dimensional vascular patterns generated by these processes in the mesentery are consistent with experimental observations. During early development of the brain, a mesh-like network of vessels is formed on the surface of the cerebral cortex. This network then forms branches into the cortex, forming a three-dimensional network throughout its thickness. Here, a theoretical model is presented for this process, based on known or hypothesized vascular response mechanisms together with experimentally obtained information on the structure and hemodynamics of the mouse cerebral cortex. According to this model, essential components of the system include sensing of oxygen levels in the midrange of partial pressures and conducted responses in vessel walls that propagate information about metabolic needs of the tissue to upstream segments of the network. The model provides insights into the effects of deficits in vascular response mechanisms, and can be used to generate physiologically realistic microvascular network structures.

[Is Neuron-Vascular Communication Disturbed in the Delayed Prenatal Brain Development of a Mouse Model of Down Syndrome?]

Developmental retardation of the brain with reduced cortical neurogenesis is observed in Ts1Cje mice, a model of Down syndrome (DS) as it is in people with DS; however, the mechanisms and the responsible gene(s) remain unknown. The goal of the present study is to establish a therapeutic approach for treating the delayed brain development in DS. To achieve this, we have utilized multiple OMICS analyses, including proteomics and transcriptomics, to uncover the molecular alterations in the brains of DS model mice. Furthermore, we have elucidated that a transcriptional factor, the Erg gene, which is coded in the trisomic region, contributed to reduced cortical neurogenesis in the embryo of a DS mouse model by a molecular genetic technique, the "in vivo gene subtraction method". In the current review, I will introduce our recent work, the identification of the gene responsible for delayed brain development in the DS mouse model and will discuss the possibility that blood vessel dysfunction may be associated with reduced embryonic neurogenesis in DS.

A Novel Hyperspectral Imaging System for Intraoperative Prediction of Cerebral Hyperperfusion Syndrome after Superficial Temporal Artery-Middle Cerebral Artery Anastomosis in Patients with Moyamoya Disease.

BACKGROUND: Postoperative cerebral hyperperfusion syndrome (CHS) may occur after superficial temporal artery (STA)-middle cerebral artery (MCA) bypass for moyamoya disease (MMD). Predicting postoperative CHS is challenging; however, we previously reported the feasibility of using a hyperspectral camera (HSC) for monitoring intraoperative changes in brain surface hemodynamics during STA-MCA bypass. OBJECTIVE: To investigate the utility of HSC to predict postoperative CHS during STA-MCA bypass for patients with MMD. METHODS: Hyperspectral images of the cerebral cortex of 29 patients with MMD who underwent STA-MCA bypass were acquired by using an HSC before and after anastomosis. We then analyzed the changes in oxygen saturation after anastomosis and assessed its correlation with CHS. RESULTS: Five patients experienced transient neurological deterioration several days after surgery. 123I-N-Isopropyl-iodoamphetamine single-photon emission computed tomography scan results revealed an intense, focal increase in cerebral blood flow at the site of anastomosis without any cerebral infarction. Patients with CHS showed significantly increased oxygen saturation (SO2) in the cerebral cortex after anastomosis relative to those without CHS (33 ± 28 vs. 8 ± 14%, p < 0.0001). Receiver operating characteristic analysis results show that postoperative CHS likely occurs when the increase rate of cortical SO2 value is >15% (sensitivity, 85.0%; specificity, 81.3%; area under curve, 0.871). CONCLUSIONS: This study indicates that hyperspectral imaging of the cerebral cortex may be used to predict postoperative CHS in patients with MMD undergoing STA-MCA bypass.

Transient Receptor Potential Melastatin 3 Is Functionally Expressed in Oligodendrocyte Precursor Cells and Is Upregulated in Ischemic Demyelinated Lesions.

Oligodendrocyte precursor cells (OPCs) are glial cells that differentiate into oligodendrocytes and myelinate axons. The number of OPCs is reportedly increased in brain lesions in some demyelinating diseases and during ischemia; however, these cells also secrete cytokines and elicit both protective and deleterious effects in response to brain injury. The mechanism regulating the behaviors of OPCs in physiological and pathological conditions must be elucidated to control these cells and to treat demyelinating diseases. Here, we focused on transient receptor potential melastatin 3 (TRPM3), a Ca2+-permeable channel that is activated by the neurosteroid pregnenolone sulfate (PS) and body temperature. Trpm3+/Pdgfra+ OPCs were detected in the cerebral cortex (CTX) and corpus callosum (CC) of P4 and adult rats by in situ hybridization. Trpm3 expression was detected in primary cultured rat OPCs and was increased by treatment with tumor necrosis factor α (TNFα). Application of PS (30-100 µM) increased the Ca2+ concentration in OPCs and this effect was inhibited by co-treatment with the TRP channel blocker Gd3+ (100 µM) or the TRPM3 inhibitor isosakuranetin (10 µM). Stimulation of TRPM3 with PS (50 µM) did not affect the differentiation or migration of OPCs. The number of Trpm3+ OPCs was markedly increased in demyelinated lesions in an endothelin-1 (ET-1)-induced ischemic rat model. In conclusion, TRPM3 is functionally expressed in OPCs in vivo and in vitro and is upregulated in inflammatory conditions such as ischemic insults and TNFα treatment, implying that TRPM3 is involved in the regulation of specific behaviors of OPCs in pathological conditions.

Quantitative protein expression of blood-brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer.

This study determined absolute transporter protein abundances in isolated microvessels of human noncancerous cerebral cortex as well as brain metastases of patients with lung and breast cancer, using a validated targeted proteomics approach. As compared with those in microvessels of noncancerous cerebral cortex, the median protein abundances of glucose transporter 1 (a brain endothelial marker) and sodium-potassium pump (Na/K ATPase, a plasma membrane marker) were decreased by ~ 80% in brain metastasis microvessels. The major efflux transporters (ABCB1 and ABCG2) fell to undetectable in microvessels of more than 80% of brain metastasis specimens. Monocarboxylate transporter 1 was undetectable in microvessels of more than 80% of brain metastases, whereas large neutral amino acid transporter 1 levels remained unchanged. In conclusion, the integrity of the physical and biochemical barrier with respect to transporter protein expression is largely disrupted in brain metastasis tumor vasculatures. Differential transporter protein abundances at the blood-brain barrier and blood-brain tumor barrier provided mechanistic and quantitative basis for prediction of heterogeneous drug penetration into human brain and brain tumors, which is critical not only to the understanding of the success or failure of systemic chemotherapy in the treatment of brain tumors but also to the development of more effective therapeutic strategies.

Mild hypoxia triggers transient blood-brain barrier disruption: a fundamental protective role for microglia.

We recently demonstrated that when mice are exposed to chronic mild hypoxia (CMH, 8% O2), blood vessels in the spinal cord show transient vascular leak that is associated with clustering and activation of microglia around disrupted vessels. Importantly, microglial depletion profoundly increased hypoxia-induced vascular leak, implying that microglia play a critical role maintaining vascular integrity in the hypoxic spinal cord. The goal of the current study was to examine if microglia play a similar vasculo-protective function in the brain. Employing extravascular fibrinogen leak as an index of blood-brain barrier (BBB) disruption, we found that CMH provoked transient vascular leak in cerebral blood vessels that was associated with activation and aggregation of Mac-1-positive microglia around leaky vessels. Interestingly, CMH-induced vascular leak showed regional selectivity, being much more prevalent in the brainstem and olfactory bulb than the cerebral cortex and cerebellum. Pharmacological depletion of microglia with the colony stimulating factor-1 receptor inhibitor PLX5622, had no effect under normoxic conditions, but markedly increased hypoxia-induced cerebrovascular leak in all regions examined. As in the spinal cord, this was associated with endothelial induction of MECA-32, a marker of leaky CNS endothelium, and greater loss of endothelial tight junction proteins. Brain regions displaying the highest levels of hypoxic-induced vascular leak also showed the greatest levels of angiogenic remodeling, suggesting that transient BBB disruption may be an unwanted side-effect of hypoxic-induced angiogenic remodeling. As hypoxia is common to a multitude of human diseases including obstructive sleep apnea, lung disease, and age-related pulmonary, cardiac and cerebrovascular dysfunction, our findings have important translational implications. First, they point to a potential pathogenic role of chronic hypoxia in triggering BBB disruption and subsequent neurological dysfunction, and second, they demonstrate an important protective role for microglia in maintaining vascular integrity in the hypoxic brain.

Protein LY6E as a candidate for mediating transport of adeno-associated virus across the human blood-brain barrier.

The blood-brain barrier (BBB) is a major obstacle for the treatment of central nervous system (CNS) disorders. Significant progress has been made in developing adeno-associated virus (AAV) variants with increased ability to cross the BBB in mice. However, these variants are not efficacious in non-human primates. Herein, we employed various bioinformatic techniques to identify lymphocyte antigen-6E (LY6E) as a candidate for mediating transport of AAV across the human BBB based on the previously determined mechanism of transport in mice. Our results provide insight into future discovery and optimization of AAV variants for CNS gene delivery in humans.

Astrocytic neogenin/netrin-1 pathway promotes blood vessel homeostasis and function in mouse cortex.

Astrocytes have multiple functions in the brain, including affecting blood vessel (BV) homeostasis and function. However, the underlying mechanisms remain elusive. Here, we provide evidence that astrocytic neogenin (NEO1), a member of deleted in colorectal cancer (DCC) family netrin receptors, is involved in blood vessel homeostasis and function. Mice with Neo1 depletion in astrocytes exhibited clustered astrocyte distribution and increased BVs in their cortices. These BVs were leaky, with reduced blood flow, disrupted vascular basement membranes (vBMs), decreased pericytes, impaired endothelial cell (EC) barrier, and elevated tip EC proliferation. Increased proliferation was also detected in cultured ECs exposed to the conditioned medium (CM) of NEO1-depleted astrocytes. Further screening for angiogenetic factors in the CM identified netrin-1 (NTN1), whose expression was decreased in NEO1-depleted cortical astrocytes. Adding NTN1 into the CM of NEO1-depleted astrocytes attenuated EC proliferation. Expressing NTN1 in NEO1 mutant cortical astrocytes ameliorated phenotypes in blood-brain barrier (BBB), EC, and astrocyte distribution. NTN1 depletion in astrocytes resulted in BV/BBB deficits in the cortex similar to those in Neo1 mutant mice. In aggregate, these results uncovered an unrecognized pathway, astrocytic NEO1 to NTN1, not only regulating astrocyte distribution, but also promoting cortical BV homeostasis and function.

PPAR-γ Mediates Ta-VNS-Induced Angiogenesis and Subsequent Functional Recovery after Experimental Stroke in Rats.

BACKGROUND: Neoangiogenesis after cerebral ischemia in mammals is insufficient to restore neurological function, illustrating the need to design better strategies for improving outcomes. Our previous study has suggested that transcutaneous auricular vagus nerve stimulation (ta-VNS) induced angiogenesis and improved neurological functions in a rat model of cerebral ischemia/reperfusion (I/R) injury. However, the mechanisms involved need further exploration. Peroxisome proliferator-activated receptor-γ (PPAR-γ), well known as a ligand-modulated nuclear transcription factor, plays a crucial role in the regulation of cerebrovascular structure and function. Hence, the present study was designed to explore the role of PPAR-γ in ta-VNS-mediated angiogenesis and uncover the possible molecular mechanisms against ischemic stroke. METHODS: Adult male Sprague-Dawley rats were transfected with either PPAR-γ small interfering RNA (siRNA) or lentiviral vector without siRNA prior to surgery and subsequently received ta-VNS treatment. The expression and localization of PPAR-γ in the ischemic boundary after ta-VNS treatment were examined. Subsequently, neurological deficit scores, neuronal damage, and infarct volume were all evaluated. Additionally, microvessel density, endothelial cell proliferation condition, and the expression of angiogenesis-related molecules in the peri-infarct cortex were measured. RESULTS: We found that the expression of PPAR-γ in the peri-infarct cortex increased at 14 d and reached normal levels at 28 d after reperfusion. Ta-VNS treatment further upregulated PPAR-γ expression in the ischemic cortex. PPAR-γ was mainly expressed in neurons and astrocytes. Furthermore, ta-VNS-treated I/R rats showed better neurobehavioral recovery, alleviated neuronal injury, reduced infarct volume, and increased angiogenesis, as indicated by the elevated levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and phosphorylated endothelial nitric oxide synthase (P-eNOS). Surprisingly, the beneficial effects of ta-VNS were weakened after PPAR-γ silencing. CONCLUSIONS: Our results suggest that PPAR-γ is a potential mediator of ta-VNS-induced angiogenesis and neuroprotection against cerebral I/R injury.

Intracranial High-Grade Stenosis and Hyperhomocysteinemia Presenting as Cortical Subarachnoid Hemorrhage Concomitant with Acute Ischemic Stroke in a Young Man.

BACKGROUND Cortical subarachnoid hemorrhage (cSAH) is a rare clinical presentation with different causes, but rarely happens along with acute ischemic stroke. Intracranial high-grade stenosis originated from brain has been regarded as an unusual cause of cSAH, especially in young adults. CASE REPORT A case of 33-year-old male presented with mild headache and spontaneous left-sided body weakness. Initial brain computed tomography (CT) showed cSAH in the right superior frontal sulcus. Further neuroimaging examinations including magnetic resonance imaging (MRI), digital subtraction angiography (DSA), transesophageal echocardiogram (TEE); in addition, lumbar puncture and blood tests were performed. Diffusion-weighted imaging (DWI) showed an acute infarction in the right frontal lobe and corona radiata of the territory of middle cerebral artery (MCA). The MR angiography (MRA) displayed no flow signal in the right middle cerebral artery M1-segment, while the DSA displayed bloodstream slowness in the right MCA M1-segment which suggested high-grade stenosis of the right MCA. The abnormal laboratory data suggested hyperhomocysteinemia, and excluded causes of thrombosis, infection, or cancer. The mechanism of cSAH may come about in severe atherosclerotic stenosis of MCAs by the broken of expanded tenuous compensatory pial vessels. The patient had good recovered at follow-up. CONCLUSIONS This case demonstrates cSAH with acute ischemic stroke, which is an uncommon complication, in a young adult stroke patient; a high-grade atherosclerotic stenosis of the MCA was identified as the etiology.

Activation of NADPH/ROS pathway contributes to angiogenesis through JNK signaling in brain endothelial cells.

Recent evidences have shown that reactive oxygen species (ROS) are involved in regulating angiogenesis and preventing tissue injury. However, the precise molecular mechanisms behind ROS-induced angiogenesis are still unknown. The aim of the present study was to investigate the effects of ROS-induced angiogenesis in rat brain microvessel endothelial cells (rBMECs) and identify involving the signal pathways. For initial experiments, the rBMECs were incubated with different concentrations of hydrogen peroxide (H2O2). For the second experiments, the rBMECs were respectively treated with ROS scavenger dimethylthiourea (DMTU), NADPH oxidase (Nox) inhibitor apocynin, small interfering RNAs-mediated knock down Nox2 or Nox4, or pretreated with c-Jun N-terminal kinase (JNK) inhibitor SP600125. The cell proliferation, migration, tube formation, and the expressions of several important neuroangiogenic factors including vascular endothelial growth factor (VEGF), brain derived neurotrophic factor (BDNF), matrix metalloproteinase (MMP) -9 and phos-JNK were measured. Low level of H2O2 significantly promoted endothelial cell (EC) proliferation, migration and tube formation and upregulated levels of VEGF, BDNF, MMP-9 and phos-JNK. DMTU and apocynin significantly inhibited endothelial angiogenesis and downregulated these protein levels. As expected, knockdown of Nox2 or Nox4 expression blocked endothelial angiogenesis and downregulated the expressions of pro-neuroangiogenic factors. Furthermore, H2O2-induced endothelial angiogenesis and high expressions of pro-neuroangiogenic factors were decreased by SP600125. In conclusion, Nox-derived ROS were required for endothelial angiogenesis. Low level of ROS may activate JNK signaling pathway and upregulate pro-neuroangiogenic factors, ultimately mediating endothelial angiogenesis.

miR-211-5p alleviates focal cerebral ischemia-reperfusion injury in rats by down-regulating the expression of COX2.

The present study was to investigate the role of microRNA (miR)-211-5p on cerebral ischemia-reperfusion injury (CIRI) and clarify its underlying mechanisms. Middle cerebral artery occlusion/reperfusion (MCAO/R) was operated on male Sprague Dawley (SD) rats, oxygen-glucose deprivation/reperfusion (OGD/R) was conducted on pheochromocytoma-12 (PC12) cells. Here, we found that miR-211-5p and Cyclooxygenase (COX2) expressions were altered in the plasma, cortex and hippocampus of MCAO/R-treated rats, as well as in the OGD/R-treaded PC12 cells. In vivo, overexpression of miR-211-5p resulted in decrease of infarct volumes, neurological deficit scores and histopathological damage. In vitro, miR-211-5p overexpression significantly decreased cell apoptosis and Lactate dehydrogenase (LDH) release rate, increased cell viability. Furthermore, our data showed that miR-211-5p overexpression markedly reduced the expressions of COX2 mRNA and protein, and the contents of Prostaglandin D2 (PGD2), PGE2, tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß). In addition, inhibition of COX2 significantly rescued the effects of miR-211-5p inhibitor. At last, dual luciferase experimental data showed that miR-211-5p regulated the mRNA stability of COX2 by directly binding to the 3'-untranslated region (3'-UTR) of COX2. In conclusion, our data suggested the neuroprotective effects of miR-211-5p on CIRI by targeting COX2.

Metabolic and perfusion responses to acute hypoglycemia in the rat cortex: A non-invasive magnetic resonance approach.

Hypoglycemia is critical condition during diabetic treatment that involves intensive insulin therapy, and it may impair brain function. We aimed to compare cortical responses of three hypoglycemic phases and the restoration of glycemia to control levels after a severe episode in rats using non-invasive perfusion magnetic resonance (MR) imaging and localized 1 H MR spectroscopy. Under light α-chloralose anesthesia, cortical blood flow (cCBF) was 42 ± 3 ml/100 g/min at euglycemia (~ 5 mM plasma glucose), was not altered at mild hypoglycemia I (42 ± 4 ml/100 g/min, 2-3.5 mM), increased to 60 ± 8 ml/100 g/min under moderate hypoglycemia II (1-2 mM) and amplified to 190 ± 35 ml/100 g/min at severe hypoglycemia III (< 1 mM). 1 H MRS revealed metabolic changes at hypoglycemia I without any perfusion alteration. At hypoglycemia III, glutamine and glutamate decreased, whereas aspartate increased. When animals subsequently regained glycemic control, not all metabolites returned to their control levels, for example, glutamine. Meanwhile, ascorbate was increased with amplified hypoglycemic severity, whereas glutathione was reduced; these compounds did not return to normal levels upon the restoration of glycemia. Our study is the first to report cCBF and neurochemical changes in cortex upon five glycemic stages. The cortical responses of different hypoglycemic phases would explain variable neuronal damages after hypoglycemia and might help identify the degrees of hypoglycemic insults and further improve alternative therapies.

Sylvian and Insular Exposure in the Extended Minipterional Approach: Landmarks, Benefits, and Quantitative Analysis Using a Cadaveric Study.

OBJECTIVE: The minipterional approach (MPTa) has been widely accepted as a minimally invasive technique in the treatment of anterior and middle cranial fossa lesions. However, this craniotomy does not facilitate exposure of the distal sylvian fissure or wide sylvian dissection. We have described a modification of the MPTa, the extended minipterional approach (eMPTa), which results in improved access to the distal sylvian fissure with minimal additional bony removal. We have defined the ideal posterior landmark for this craniotomy, the preauricular line, using an anatomic cadaveric study. METHODS: The insular and sylvian exposure offered by the MPTa and eMPTa were compared in 5 cadaveric heads. Anatomic exposure of the eMPTa and its anatomic relation to different landmarks were also evaluated. RESULTS: The eMPTA, extending posteriorly to the preauricular line, offers improved surgical exposure of the sylvian fissure (30.5 vs. 13 mm; P < 0.001) and insula (31 vs. 10 mm; P < 0.001) compared with the MPTa. The frontal precentral artery, an important landmark for performing distal-to-proximal sylvian dissection, is 17 ± 5.2 mm anterior to the preauricular line, the posterior limit of the eMPTa. In contrast, it is 6.5 ± 3.6 mm posterior to the traditional posterior limit of the MPTa. CONCLUSION: The eMPTA offers improved access to the sylvian fissure, allowing for wider fissure splitting and only requiring extension of the posterior limit of the MPT craniotomy up to the preauricular line. This could allow for improved freedom of movement deep in the sylvian cistern and potentially expand the indications of the MPTa.

[Neuro-vascular Interactions during Neocortical Development-Systematic and Accurate Regulatory Mechanisms of VEGF Signaling].

Blood vessels supply oxygen and nutrients to all the cells in a living body, and provide essential transport routes for collecting waste products. For these functions, blood vessel networks should be appropriately formed in each tissue. Therefore, blood vessels are one of the earliest organs formed during the developmental process. Development of the blood vessel system promotes tissue differentiation and organ morphogenesis, allowing each organ to maintain its unique functions under changing metabolic conditions. Blood vessels have a relatively simple structure, consisting of endothelial cells covering the inner layer, and pericytes or smooth muscle cells surrounding the outside. The structure of the vascular network is extremely diverse, with blood vessels uniquely organized depending on the tissues they serve, to create tissue-specific microenvironments. How are such tissue-specific vascular environments generated? Over the years, anatomical findings have accumulated to confirm this vascular diversity. However, the molecular basis for this diversity has remained unclear. In the present article, we review the mechanisms of coordinated developmental control of the vascular and neural systems in the cerebral cortex from the viewpoint of the accurate expression control of vascular endothelial growth factor (VEGF) signaling, and describe future perspectives.