PHEV infection: A promising model of betacoronavirus-associated neurological and olfactory dysfunction.

Porcine hemagglutinating encephalomyelitis virus (PHEV) is a highly neurotropic coronavirus belonging to the genus Betacoronavirus. Similar to pathogenic coronaviruses to which humans are susceptible, such as SARS-CoV-2, PHEV is transmitted primarily through respiratory droplets and close contact, entering the central nervous system (CNS) from the peripheral nerves at the site of initial infection. However, the neuroinvasion route of PHEV are poorly understood. Here, we found that BALB/c mice are susceptible to intranasal PHEV infection and showed distinct neurological manifestations. The behavioral study and histopathological examination revealed that PHEV attacks neurons in the CNS and causes significant smell and taste dysfunction in mice. By tracking neuroinvasion, we identified that PHEV invades the CNS via the olfactory nerve and trigeminal nerve located in the nasal cavity, and olfactory sensory neurons (OSNs) were susceptible to viral infection. Immunofluorescence staining and ultrastructural observations revealed that viral materials traveling along axons, suggesting axonal transport may engage in rapid viral transmission in the CNS. Moreover, viral replication in the olfactory system and CNS is associated with inflammatory and immune responses, tissue disorganization and dysfunction. Overall, we proposed that PHEV may serve as a potential prototype for elucidating the pathogenesis of coronavirus-associated neurological complications and olfactory and taste disorders.

Flexible SERS Biosensor Based on Core-Shell Nanotags for Sensitive and Multiple Detection of T1DM Biomarkers.

Sensitive and multiple detection of the biomarkers of type 1 diabetes mellitus (T1DM) is vital to the early diagnosis and clinical treatment of T1DM. Herein, we developed a SERS-based biosensor using polyvinylidene fluoride (PVDF) membranes as a flexible support for the detection of glutamic acid decarboxylase antibodies (GADA) and insulin autoantibodies (IAA). Two kinds of silver-gold core-shell nanotags embedded with Raman probes and attached with GADA or IAA antibodies were synthesized to capture the targets, enabling highly sensitive and highly selective detection of GADA and IAA. The embedded Raman probes sandwiched between silver and gold layers guaranteed spectral stability and reliability. Moreover, the utilization of two Raman probes enables simultaneous and multiplexing detection of both GADA and IAA, improving the detection accuracy for T1DM. The proposed SERS-based method has been proven feasible for clinical sample detection, demonstrating its great potential in sensitive, reliable, and rapid diagnosis of T1DM.

Dynamic Cerebral Autoregulation After Carotid Endarterectomy.

OBJECTIVE: Studies have shown that dynamic cerebral autoregulation (dCA) is impaired in patients with severe internal carotid artery (ICA) stenosis and that carotid endarterectomy (CEA) may improve dCA in these patients. However, the time course of dCA changes in patients after CEA remains unclear. Therefore, this study aimed to investigate the effects of CEA on the dCA in patients with carotid artery stenosis at different time points. METHODS: This prospective study enrolled 44 patients (19 symptomatic stenosis patients and 25 asymptomatic stenosis patients) who underwent CEA and 44 age- and sex-matched controls. In the CEA group, the patients underwent dCA measurements at baseline, within 3 days, and 1 month after CEA. Transfer function parameters, phase difference (PD), and gain were used to quantify dCA. Changes in dCA before and after CEA were analyzed in detail. RESULTS: The bilateral PD of the patients before CEA was significantly lower than that of the control group. This damage did not improve within 3 days after surgery. One month after surgery, the PD on the affected side of the patients significantly improved compared with before surgery and reached the level of the control group. The PD of affected side across time points in symptomatic and asymptomatic stenosis patients is consistent with that in all patients. CONCLUSIONS: The dCA level did not improve immediately after CEA but significantly improved 1 month after surgery. This suggests that the occurrence of stroke should be considered in the acute period after CEA surgery, and its preventive effect on stroke may be effective after 1 month. CLINICAL IMPACT: We found the dCA level did not improve immediately after CEA but significantly improved 1 month after surgury. This suggests that the occuttencce of stroke and surgical complications (such as cerebral hyperperfusion syndrome) associated with impaired dCA in the acute phase after CEA surgery should be of particular concern.

Analysis of the complete genome sequence of Lactobacillus delbrueckii ssp. bulgaricus with post-acidification capacity and its influence on yogurt in storage.

In recent years, yogurt has been one of the most popular fermented dairy products and is sold worldwide. In this study, pH and titrated acid changes of 4 strains of Lactobacillus delbrueckii ssp. bulgaricus fermented milk during storage were detected. The difference between L. bulgaricus KLDS1.1011 and KLDS1.0207 was significant, with the latter exhibiting reduced acidity levels. Therefore, we determined the complete genome sequence of the 2 strains. Then the expression of specific genes and common genes related to glucose metabolism and proteolysis of L. bulgaricus KLDS1.1011 and KLDS1.0207 were detected by quantitative real-time reverse-transcription PCR. Analysis indicated that the key enzymes in glycometabolism and proteolysis of L. bulgaricus KLDS1.1011 were significantly different than those of L. bulgaricus KLDS1.0207. The contents of lactose and glucose decreased during storage of L. bulgaricus fermented milk, as determined by HPLC, and the contents of lactic acid and galactose increased, with L. bulgaricus KLDS1.1011 increasing less. With skim milk as a raw material, L. bulgaricus KLDS1.1011, KLDS1.0207, and Streptococcus thermophilus S1 were used as fermentation strains to yield yogurt at 42°C, and sensory evaluation was compared with yogurt fermented by commercial starter cultures. Yogurt from L. bulgaricus KLDS1.1011 was the highest-rated. Therefore, the study may provide guidelines for the development of yogurt starters.

Colorimetric assay of phosphate using a multicopper laccase-like nanozyme.

A new nanozyme (Cu-NADH) is reported composed of Cu-coordinated nicotinamide adenine dinucleotide (NADH) exhibiting laccase-like activity. The Cu-NADH nanozyme had higher heat tolerance and catalytic efficiency than natural laccase, and its catalytic activity can be enhanced by high concentration of Cl ions and it is intensely inhibited by phosphate. Therefore, a colorimetric method based on Cu-NADH and indigo carmine was successfully developed to detect phosphate in water. This method showed an excellent selectivity for phosphate, and it had a linear relationship in the phosphate concentration range 2-50 µM with a detection limit of 0.37 µM. We believe that this example of coordination between metal ions and biomolecules to mimic natural enzymes can inspire more effective and alternative strategies in nanozyme design and expand their use in sensing and determination.

Neuroprotective Effect of Ginseng Fibrous Root Enzymatic Hydrolysate against Oxidative Stress.

Oxidative stress is one of the potential causes of nervous system disease. Ginseng extract possesses excellent antioxidant activity; however, little research on the function of the ginseng fibrous root. This study aimed to investigate the neuroprotective effects of ginseng fibrous root to alleviate the pathogenesis of Alzheimer's disease (AD) against oxidative stress. Ginseng fibrous root enzymatic hydrolysate (GFREH) was first prepared by digesting ginseng fibrous roots with alkaline protease. In vitro, the GFREH showed antioxidant activities in free radical scavenging mechanisms. With a cellular model of AD, GFREH inhibited the increase in Ca2+ levels and intracellular ROS content, maintained the balance of mitochondrial membrane potential, and relieved L-glutamic acid-induced neurotoxicity. In vivo, GFREH improved the survival rate of Caenorhabditis elegans (C. elegans) under oxidative stress, upregulated SOD-3 expression, and reduced reactive oxygen species (ROS) content. Therefore, our findings provide evidence for the alleviation effect of GFREH against oxidative stress in neuroprotection, which may accelerate the development of anti-Alzheimer's drugs and treatments in the future.

Endovascular treatment of blunt injury of the extracranial internal carotid artery: the prospect and dilemma.

The extracranial internal carotid artery (ICA) refers to the anatomic location that reaches from the common carotid artery proximally to the skull base distally. The extracranial ICA belongs to the C1 segment of the Bouthillier classification and is at considerable risk for injury. Currently, the understanding of endovascular treatment (EVT) for blunt injury of the extracranial ICA is limited, and a comprehensive review is therefore important. In this review, we found that extracranial ICA blunt injury should be identified in patients presenting after blunt trauma, including classical dissection, pseudoaneurysm, and stenosis/occlusion. Computed tomography angiography (CTA) is the first-line method for screening for extracranial ICA blunt injury, although digital subtraction angiography (DSA) remains the "gold standard" in imaging. Antithrombotic treatment is effective for stroke prevention. However, routine EVT in the form of stenting should be reserved for patients with prolonged neurological symptoms from arterial stenosis or considerably enlarged pseudoaneurysm. Endovascular repair is now emerging as a favored therapeutic option given its demonstrated safety and positive clinical and radiographic outcomes.

Retraction Note: Bone mesenchymal stem cell-derivedexosomal microRNA-29b-3p preventshypoxic-ischemic injury in rat brain byactivating the PTEN-mediated Aktsignaling pathway.

An amendment to this paper has been published and can be accessed via the original article.

Correction to: Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway.

An amendment to this paper has been published and can be accessed via the original article.

Bone mesenchymal stem cell-derived exosomal microRNA-29b-3p prevents hypoxic-ischemic injury in rat brain by activating the PTEN-mediated Akt signaling pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) are suspected to exert neuroprotective effects in brain injury, in part through the secretion of extracellular vesicles like exosomes containing bioactive compounds. We now investigate the mechanism by which bone marrow MSCs (BMSCs)-derived exosomes harboring the small non-coding RNA miR-29b-3p protect against hypoxic-ischemic brain injury in rats. METHODS: We established a rat model of middle cerebral artery occlusion (MCAO) and primary cortical neuron or brain microvascular endothelial cell (BMEC) models of oxygen and glucose deprivation (OGD). Exosomes were isolated from the culture medium of BMSCs. We treated the MCAO rats with BMSC-derived exosomes in vivo, and likewise the OGD-treated neurons and BMECs in vitro. We then measured apoptosis- and angiogenesis-related features using TUNEL and CD31 immunohistochemical staining and in vitro Matrigel angiogenesis assays. RESULTS: The dual luciferase reporter gene assay showed that miR-29b-3p targeted the protein phosphatase and tensin homolog (PTEN). miR-29b-3p was downregulated and PTEN was upregulated in the brain of MCAO rats and in OGD-treated cultured neurons. MCAO rats and OGD-treated neurons showed promoted apoptosis and decreased angiogenesis, but overexpression of miR-29b-3p or silencing of PTEN could reverse these alterations. Furthermore, miR-29b-3p could negatively regulate PTEN and activate the Akt signaling pathway. BMSCs-derived exosomes also exerted protective effects against apoptosis of OGD neurons and cell apoptosis in the brain samples from MCAO rats, where we also observed promotion of angiogenesis. CONCLUSION: BMSC-derived exosomal miR-29b-3p ameliorates ischemic brain injury by promoting angiogenesis and suppressing neuronal apoptosis, a finding which may be of great significance in the treatment of hypoxic-ischemic brain injury.

Angiographic study of the transdural collaterals at the anterior cranial fossa in patients with Moyamoya disease.

Unlike its parietal, temporal, and occipital counterparts, the frontal lobe has a broad basal surface directly facing the anterior cranial fossa dura mater which could permit establishment of transdural collaterals (TDCs) with the frontal lobe. Studies on the TDCs from the anterior cranial fossa in moyamoya disease (MMD) are scarce and inadequately investigated. A retrospective study of 100 hemispheres in 50 patients who were diagnosed with MMD by catheter angiography between January 2015 and June 2019 was performed in our institution. TDCs through the anterior ethmoid artery (AEA) or posterior ethmoid artery (PEA) were divided into 3 types respectively based on their respective angioarchitecture. Furthermore, we also studied TDCs to the temporal, parietal, and occipital lobes and collaterals from the posterior circulation to the territory of the anterior cerebral artery. TDCs through the AEA and PEA were identified in 89 (89/100, 89%) and 73 (73/100, 73%) of the hemispheres. The vascularization state of the frontal lobe was good in 89 (89/100, 89%) hemispheres. Rete mirabile and TDCs through the PEA were statistically different among patients with different Suzuki stages. No statistical difference was noted in TDCs through the AEA, frontal TDCs from other sources, and the vascularization state of the frontal lobe with regard to different Suzuki stages. TDCs through the AEA and PEA at the anterior cranial fossa play a very important role in compensating the ischemic frontal lobe. The frontal lobe could be well compensated in most of the patients with TDCs at the anterior cranial fossa.

A Novel Putative Role of TNK1 in Atherosclerotic Inflammation Implicating the Tyk2/STAT1 Pathway.

OBJECTIVE: Atherosclerosis is a chronic inflammatory disease which is responsible for many clinical manifestations. The present study was to investigate the anti-inflammatory functions and mechanisms of TNK1 in atherosclerosis. METHODS: The ApoE(-/-) mice and human carotid endarterectomy (CEA) atherosclerotic plaques were used to investigate the differential expression of TNK1. The ApoE(-/-) mice were fed with high-fat diet (HFD) or normal-fat diet (NFD) for 8 weeks; the aorta was separated and stained with oil red O to evaluate the formation of atherosclerosis. TNK1 in mice aorta was measured by qPCR. The human CEA were obtained and identified as ruptured and stable plaques. The level of TNK1 was measured by qPCR and Western-blot staining. Further studies were conducted in THP-1 cells to explore the anti-inflammatory effects of TNK1. We induced the formation of macrophages by incubating THP-1 cells with PMA (phorbol 12-myristate 13-acetate). Afterwards, oxidized low-density lipoprotein (oxLDL) was used to stimulate the inflammation, and the secretion of inflammatory factors was measured by ELISA and qPCR. The levels of TNK1, total STAT1 and Tyk2, and the phosphorylation of STAT1 and Tyk2 were measured by western blot to uncover the mechanisms of TNK1. RESULTS: The oil red O staining indicated obvious deposition of lipid on the aorta of ApoE(-/-) mice after 8-week HFD treatment. The TNK1 level was much higher in both the HFD-fed ApoE(-/-) mice aorta arch and the ruptured human CEA plaques. We found that TNK1 was highly expressed in THP-1 cells, compared to other atherosclerotic related cells (HUVEC, HBMEC, and HA-VSMC), indicating TNK1 might be involved in the inflammation. Suppressing the expression of TNK1 by shTNK1 inhibited the oxLDL-induced secretion of inflammatory factors, such as IL-12, IL-6, and TNF-α. ShTNK1 also inhibited the uptake of lipid and decreased the cellular cholesterol content in THP-1 cells. Furthermore, the shTNK1 suppressed the oxLDL-induced phosphorylation of Tyk2 and STAT1. CONCLUSION: TNK1 participated in the inflammation in atherosclerosis. shTNK1 suppressed the oxLDL-induced inflammation and lipid deposition in THP-1 cells. The mechanism might be related to the Tyk2/STAT signal pathway.

Blockade of the swelling-induced chloride current attenuates the mouse neonatal hypoxic-ischemic brain injury in vivo.

Activation of swelling-induced Cl- current (ICl,swell) during neonatal hypoxia-ischemia (HI) may induce brain damage. Hypoxic-ischemic brain injury causes chronic neurological morbidity in neonates as well as acute mortality. In this study, we investigated the role of ICl,swell in hypoxic-ischemic brain injury using a selective blocker, 4-(2-butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl) oxybutyric acid (DCPIB). In primary cultured cortical neurons perfusion of a 30% hypotonic solution activated ICl,swell, which was completely blocked by the application of DCPIB (10 µmol/L). The role of ICl,swell in neonatal hypoxic-ischemic brain injury in vivo was evaluated in a modified neonatal hypoxic-ischemic brain injury model. Before receiving the ischemic insult, the mouse pups were injected with DCPIB (10 mg/kg, ip). We found that pretreatment with DCPIB significantly reduced the brain damage assessed using TTC staining, Nissl staining and whole brain imaging, and improved the sensorimotor and vestibular recovery outcomes evaluated in neurobehavioural tests (i.e. geotaxis reflex, and cliff avoidance reflex). These results show that DCPIB has neuroprotective effects on neonatal hypoxic-ischemic brain injury, and that the ICl,swell may serve as a therapeutic target for treatment of hypoxic-ischemic encephalopathy.

Current Understanding of Dolichoarteriopathies of the Internal Carotid Artery: A Review.

Dolichoarteriopathies of the internal carotid artery (DICAs) are not uncommon, and although several studies have investigated DICAs, several questions regarding the etiology and best management course for DICAs remain unanswered. It is also difficult to correlate the occurrence of DICAs with the onset of clinical symptoms. Therefore, we surveyed the literature in PubMed and performed a review of DICAs to offer a comprehensive picture of our understanding of DICAs. We found that DICAs can be classified into three types, specifically tortuous, coiling and kinking, and are not associated with atherosclerotic risk factors. Cerebral hemodynamic changes are mainly associated with the degree of bending of DICAs. DICAs can result in symptoms of the brain and eyes due to insufficient blood supply and can co-occur with a pulsatile cervical mass, a pharyngeal bulge and pulsation. The diagnostic tools for the assessment of DICAs include Doppler ultrasonography, computed tomography angiography (CTA), magnetic resonance angiography (MRA) and digital subtraction angiography (DSA), and although DSA remains the gold standard, Doppler ultrasonography is a convenient method that provides useful data for the morphological evaluation of DICAs. CTA and MRA are efficient methods for detecting the morphology of the cervical segment of DICAs. Some DICAs should be treated surgically based on certain indications, and several methods, including correcting the bending or shortening of DICAs, have been developed for the treatment of DICAs. The appropriate treatment of DICAs results in good outcomes and is associated with low morbidity and mortality rates. However, despite the success of surgical reconstruction, an appropriate therapeutic treatment remains a subject of numerous debates due to the lack of multicentric, randomized, prospective studies.

Current status of the treatment of blood blister-like aneurysms of the supraclinoid internal carotid artery: A review.

Currently, the treatment of blood blister-like aneurysms (BBAs) of the supraclinoid internal carotid artery (ICA) is challenging and utilizes many therapeutic methods, including direct clipping and suturing, clipping after wrapping, clipping after suturing, coil embolization, stent-assisted coil embolization, multiple overlapping stents, flow-diverting stents, covered stents, and trapping with or without bypass. In these therapeutic approaches, the optimal treatment method for BBAs has not yet been defined based on the current understanding of BBAs of the supraclinoid ICA. Therefore, in this study, we aimed to review the literature from PubMed to discuss and analyze the pros and cons of the above approaches while adding our own viewpoints to the discussion. Among the surgical methods, direct clipping was the easiest method if the compensation of the collateral circulation of the intracranial distal ICA was sufficient or direct clipping did not induce stenosis in the parent artery. In addition, the clipping after wrapping technique should be chosen as the optimal surgical modality to prevent rebleeding from these lesions. Among the endovascular methods, multiple overlapping stents (≥3) with coils may be a feasible alternative for the treatment of ruptured BBAs. In addition, flow-diverting stents appear to have a higher rate of complete occlusion and a lower rate of retreatment and are a promising treatment method. Finally, when all treatments failed or the compensation of the collateral circulation of the intracranial distal ICA was insufficient, the extracranial-intracranial (EC-IC) arterial bypass associated with surgical or endovascular trapping, a complex and highly dangerous method, was used as the treatment of last resort.

CCR7 regulates Twist to induce the epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma.

As reported, the CC chemokine receptor 7 (CCR7) trigger a series of signaling cascades in the epithelial-mesenchymal transition (EMT) of some malignancies. Meanwhile, Twist promotes EMT in pancreatic ductal adenocarcinoma (PDAC) progression. Here, effects of Twist on CCR7-induced EMT in the PDAC were investigated in detail. The immunohistochemistry was used to detect the expression of Twist, and then, in vitro assays were applied. The expression rate of Twist was 72.0 % in PDAC samples and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When PDAC cell line PANC1 was subjected to CCL19 stimulation, the expression of p-ERK, p-AKT, Twist, N-cadherin, MMP9, and α-smooth muscle actin (α-SMA) was induced, while the GSK1120212, BEZ235, and MK2206 prohibited the increase of Twist and EMT biomarkers. For another thing, the si-Twist treatment attenuated CCL19-stimulated EMT occurrence, migration, and invasion phenotypes of PANC1 cells. In conclusion, CCR7 pathway up-regulates Twist expression via ERK and PI3K/AKT signaling to manage the EMT of PDAC. Our work allows for clinical gene or protein-targeted regimen of PDAC patients in the near future.

The adaptor protein CrkII regulates IGF-1-induced biological behaviors of pancreatic ductal adenocarcinoma.

Recently, the adaptor protein CrkII has been proved to function in initiating signals for proliferation and invasion in some malignancies. However, the specific mechanisms underlying insulin-like growth factor 1 (IGF-1)-CrkII signaling-induced proliferation of pancreatic ductal adenocarcinoma (PDAC) were not unraveled. In this work, PDAC tissues and cell lines were subjected to in vitro and in vivo assays. Our findings showed that CrkII was abundantly expressed in PDAC tissues and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When cells were subjected to si-CrkII, si-CrkII inhibited IGF-1-mediated PDAC cell growth. In vitro, we demonstrated the upregulation of CrkII, p-Erk1/2, and p-Akt occurring in IGF-1-treated PDAC cells. Conversely, si-CrkII affected upregulation of CrkII, p-Erk1/2, and p-Akt. In addition, cell cycle and in vivo assay identified that knockdown of CrkII inhibited the entry of G1 into S phase and the increase of PDAC tumor weight. In conclusion, CrkII mediates IGF-1 signaling and further balanced PDAC biological behaviors via Erk1/2 and Akt pathway, which indicates that CrkII gene and protein may act as an effective target for the treatment of PDAC.

Clinical importance of the middle meningeal artery: A review of the literature.

The middle meningeal artery (MMA) is a very important artery in neurosurgery. Many diseases, including dural arteriovenous fistula (DAVF), pseudoaneurysm, true aneurysm, traumatic arteriovenous fistula (AVF), moyamoya disease (MMD), recurrent chronic subdural hematoma (CSDH), migraine and meningioma, can involve the MMA. In these diseases, the lesions occur in either the MMA itself and treatment is necessary, or the MMA is used as the pathway to treat the lesions; therefore, the MMA is very important to the development and treatment of a variety of neurosurgical diseases. However, no systematic review describing the importance of MMA has been published. In this study, we used the PUBMED database to perform a review of the literature on the MMA to increase our understanding of its role in neurosurgery. After performing this review, we found that the MMA was commonly used to access DAVFs and meningiomas. Pseudoaneurysms and true aneurysms in the MMA can be effectively treated via endovascular or surgical removal. In MMD, the MMA plays a very important role in the development of collateral circulation and indirect revascularization. For recurrent CDSHs, after burr hole irrigation and drainage have failed, MMA embolization may be attempted. The MMA can also contribute to the occurrence and treatment of migraines. Because the ophthalmic artery can ectopically originate from the MMA, caution must be taken to avoid causing damage to the MMA during operations.

Progress on Complications of Direct Bypass for Moyamoya Disease.

Moyamoya disease (MMD) involves progressive occlusion of the intracranial internal carotid artery resulting in formation of moyamoya-like vessels at the base of the brain. It can be characterized by hemorrhage or ischemia. Direct vascular bypass is the main and most effective treatment of MMD. However, patients with MMD differ from those with normal cerebral vessels. MMD patients have unstable intracranial artery hemodynamics and a poor blood flow reserve; therefore, during the direct bypass of superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis, perioperative risk factors and anesthesia can affect the hemodynamics of these patients. When brain tissue cannot tolerate a high blood flow rate, it becomes prone to hyperperfusion syndrome, which leads to neurological function defects and can even cause intracranial hemorrhage in severe cases. The brain tissue is prone to infarction when hemodynamic equilibrium is affected. In addition, bypass vessels become susceptible to occlusion or atrophy when blood resistance increases. Even compression of the temporalis affects bypass vessels. Because the STA is used in MMD surgery, the scalp becomes ischemic and is likely to develop necrosis and infection. These complications of MMD surgery are difficult to manage and are not well understood. To date, no systematic studies of the complications that occur after direct bypass in MMD have been performed, and reported complications are hidden among various case studies; therefore, this paper presents a review and summary of the literature in PubMed on the complications of direct bypass in MMD.

Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury.

Neonatal hypoxic-ischemic encephalopathy causes neurodegeneration and brain injury, leading to sensorimotor dysfunction. Xyloketal B is a novel marine compound isolated from a mangrove fungus Xylaria species (no. 2508) with unique antioxidant effects. In this study, we investigated the effects and mechanism of xyloketal B on oxygen-glucose deprivation-induced neuronal cell death in mouse primary cortical culture and on hypoxic-ischemic brain injury in neonatal mice in vivo. We found that xyloketal B reduced anoxia-induced neuronal cell death in vitro, as well as infarct volume in neonatal hypoxic-ischemic brain injury model in vivo. Furthermore, xyloketal B improved functional behavioral recovery of the animals following hypoxic-ischemic insult. In addition, xyloketal B significantly decreased calcium entry, reduced the number of TUNEL-positive cells, reduced the levels of cleaved caspase-3 and Bax proteins, and increased the level of Bcl-2 protein after the hypoxic-ischemic injury. Our findings indicate that xyloketal B is effective in models of hypoxia-ischemia and thus has potential as a treatment for hypoxic-ischemic brain injury.