Extracts from Dendropanax morbifera leaves ameliorates cerebral ischemia-induced hippocampal damage by reducing oxidative damage in gerbil.

AIM: In this study, we investigated the effects of Dendropanax morbifera extract (DME) on neuroprotection against ischemic damage in gerbils. METHODS: DME (100 or 300 mg/kg) was orally administered to gerbils for three weeks, and 2 h after the last DME treatment, transient forebrain ischemia in the common carotid arteries was induced for 5 min. The forebrain ischemia-related cognitive impairments were assessed by spontaneous motor activity and passive avoidance test one and four days after ischemia, respectively. In addition, surviving and degenerating neurons were morphologically confirmed by neuronal nuclei immunohistochemical staining and Fluoro-Jade C staining, respectively, four days after ischemia. Changes of glial morphology were visualized by immunohistochemical staining for each marker such as glial fibrillary acidic protein and ionized calcium-binding protein. Oxidative stress was determined by measurements of dihydroethidium, O2· (formation of formazan) and malondialdehyde two days after ischemia. In addition, glutathione redox system such as reduced glutathione, oxidized glutathione levels, glutathione peroxidase, and glutathione reductase activities were measured two days after ischemia. RESULTS: Spontaneous motor activity monitoring and passive avoidance tests showed that treatment with 300 mg/kg DME, but not 100 mg/kg, significantly alleviated ischemia-induced memory impairments. In addition, approximately 67 % of mature neurons survived and 29.3 % neurons were degenerated in hippocampal CA1 region four days after ischemia, and ischemia-induced morphological changes in astrocytes and microglia were decreased in the CA1 region after 300 mg/kg DME treatment. Furthermore, treatment with 300 mg/kg DME significantly ameliorated ischemia-induced oxidative stress, such as superoxide formation and lipid peroxidation, two days after ischemia. In addition, ischemia-induced reduction of the glutathione redox system in the hippocampus, assessed two days after the ischemia, was ameliorated by treatment with 300 mg/kg DME. These suggest that DME can potentially reduce ischemia-induced neuronal damage through its antioxidant properties.

Cu,Zn-Superoxide Dismutase has Minimal Effects Against Cuprizone-Induced Demyelination, Microglial Activation, and Neurogenesis Defects in the C57BL/6 Mouse Hippocampus.

Cuprizone causes consistent demyelination and oligodendrocyte damage in the mouse brain. Cu,Zn-superoxide dismutase 1 (SOD1) has neuroprotective potential against various neurological disorders, such as transient cerebral ischemia and traumatic brain injury. In this study, we investigated whether SOD1 has neuroprotective effects against cuprizone-induced demyelination and adult hippocampal neurogenesis in C57BL/6 mice, using the PEP-1-SOD1 fusion protein to facilitate the delivery of SOD1 protein into hippocampal neurons. Eight weeks feeding of cuprizone-supplemented (0.2%) diets caused a significant decrease in myelin basic protein (MBP) expression in the stratum lacunosum-moleculare of the CA1 region, the polymorphic layer of the dentate gyrus, and the corpus callosum, while ionized calcium-binding adapter molecule 1 (Iba-1)-immunoreactive microglia showed activated and phagocytic phenotypes. In addition, cuprizone treatment reduced proliferating cells and neuroblasts as shown using Ki67 and doublecortin immunostaining. Treatment with PEP-1-SOD1 to normal mice did not show any significant changes in MBP expression and Iba-1-immunoreactive microglia. However, Ki67-positive proliferating cells and doublecortin-immunoreactive neuroblasts were significantly decreased. Simultaneous treatment with PEP-1-SOD1 and cuprizone-supplemented diets did not ameliorate the MBP reduction in these regions, but mitigated the increase of Iba-1 immunoreactivity in the corpus callosum and alleviated the reduction of MBP in corpus callosum and proliferating cells, not neuroblasts, in the dentate gyrus. In conclusion, PEP-1-SOD1 treatment only has partial effects to reduce cuprizone-induced demyelination and microglial activation in the hippocampus and corpus callosum and has minimal effects on proliferating cells in the dentate gyrus.

The clinical necessity of a distal forearm DEXA scan for predicting distal radius fracture in elderly females: a retrospective case-control study.

BACKGROUND: Recent studies have demonstrated that the distal forearm dual-energy X-ray absorptiometry (DEXA) scan might be a better method for screening bone mineral density (BMD) and the risk of a distal forearm fracture, compared with a central DEXA scan. Therefore, the purpose of this study was to determine the effectiveness of a distal forearm DEXA scan for predicting the occurrence of a distal radius fracture (DRF) in elderly females who were not initially diagnosed with osteoporosis after a central DEXA scan. METHODS: Among the female patients who visited our institutes and who were over 50 years old and underwent DEXA scans at 3 sites (lumbar spine, proximal femur, and distal forearm), 228 patients with DRF (group 1) and 228 propensity score-matched patients without fractures (group 2) were included in this study. The patients' general characteristics, BMD, and T-scores were compared. The odds ratios (OR) of each measurement and correlation ratio among BMD values of the different sites were evaluated. RESULTS: The distal forearm T-score of the elderly females with DRF (group 1) was significantly lower than that of the control group (group 2) (p < 0.001 for the one-third radius and ultradistal radius measurements). BMD measured during the distal forearm DEXA scan was a better predictor of DRF risk than BMD measured during the central DEXA (OR = 2.33; p = 0.031 for the one-third radius, and OR = 3.98; p < 0.001 for the ultradistal radius). The distal one-third radius BMD was correlated with hip BMD, rather than lumbar BMD (p < 0.05 in each group). CONCLUSION: Performing a distal forearm DEXA scan in addition to a central DEXA scan appears to be clinically significant for detecting the low BMD in the distal radius, which is associated with osteoporotic DRF in elderly females. LEVEL OF EVIDENCE: III; case-control study.

Selective Denervation for the Thumb Carpometacarpal Joint: Clinical Outcome and Comparison Based on Eaton Stage.

PURPOSE: Various operative treatment options for advanced thumb carpometacarpal (CMC) joint arthritis have been presented without a definite surgical guideline. Selective denervation is a less invasive method for thumb CMC arthritis. However, it is unclear whether the clinical outcome varies with the stage of thumb CMC arthritis. This study aimed to evaluate the effectiveness of selective denervation on CMC arthritis for pain relief and functional outcome and to determine whether selective denervation depends on the stage of thumb CMC arthritis. METHODS: We evaluated 29 thumbs of 28 patients with thumb CMC arthritis treated with selective denervation. The disease stage was determined with the classification system described by Eaton. The denervation was performed in the articular branches of the palmar cutaneous branch of the median nerve, lateral antebrachial cutaneous nerve, and superficial branch of radial nerve. The clinical outcomes were evaluated using the visual analog scale (VAS) and Disabilities of the Arm, Shoulder, and Hand (DASH) scores, along with evaluation of the improvement in both postoperative range of motion and strength recovery. RESULTS: The mean duration of follow-up was 24 months (range, 18-48 months). The average VAS and DASH scores decreased from 6.1 to 1.3 and from 54.3 to 24.1, respectively. The range of motion during palmar abduction and opposition of the metacarpophalangeal joint improved with an increase in mean value from 44.1 to 53.7 degrees, and the Kapandji score increased from 7.2 to 9.2, respectively. The grip and key pinch strengths increased from mean preoperative values of 14.3 and 3.1 kg to 27.1 and 6.2 kg, respectively, as measured at the 12-month follow-up. The rate of change in the VAS and DASH scores was significantly higher in stages I to III than in stage IV ( P = 0.01, P < 0.01, respectively). CONCLUSION: The selective denervation for thumb CMC arthritis was effective in pain relief and functional recovery with several advantages, including less invasive procedure, quick recovery time, and regaining of strength. The clinical outcomes were more effective in the early-stage group (Eaton stages I and II) compared with the advance-stage group (Eaton stages III and IV).

Comparison of the Effects of Cuprizone on Demyelination in the Corpus Callosum and Hippocampal Progenitors in Young Adult and Aged Mice.

Cuprizone is commonly used to induce neuronal demyelination in mice. In the present study, we compared the cuprizone-induced demyelination in the corpus callosum and investigated the effects of cuprizone on proliferating cells and neuroblasts in the dentate gyrus of young adult and aged mice. 5-week- and 23-month-old mice were fed a normal diet or a 0.2% cuprizone-enriched diet for 5 weeks. Mice fed a cuprizone-supplemented diet showed a significant reduction in myelin basic protein-positive structures in the corpus callosum, with the reduction in myelinated fibers being confirmed by electron microscopic analysis. In addition, we observed a marked increase in Ki67-positive proliferating cells and doublecortin-immunoreactive neuroblasts in young adult mice in response to cuprizone treatment, although not in aged mice, as the basal levels of these cells were significantly lower in these older mice. Furthermore, Ser133-phosphorylated cAMP response element-binding protein (pCREB)-positive nuclei and brain-derived neurotrophic factor (BDNF) protein levels were significantly reduced in young adult mice following cuprizone treatment in young adult, although again not in the aged mice. However, in both young adult and aged mice, there were no significant reductions in hippocampal mature neurons in response to cuprizone treatment. These observations indicate that in the mice of both age groups a cuprizone-supplemented diet contributes to an increase in demyelination in the corpus callosum and neural progenitor cells in the dentate gyrus, although the damage is more pronounced in young adult mice. This demyelination and reduction in neural progenitor cells may be associated with changes in the levels of BDNF and pCREB in the dentate gyrus.

Phase-only hologram video compression using a deep neural network for up-scaling and restoration.

This paper proposes a coding method for compressing a phase-only hologram video (PoHV), which can be directly displayed in a commercial phase-only spatial light modulator. Recently, there has been active research to use a standard codec as an anchor to develop a new video coding for 3D data such as MPEG point cloud compression. The main merit of this approach is that if a new video codec is developed, the performance of relative coding methods can be increased simultaneously. Furthermore, compatibility is increased by the capability to use various anchor codecs, and the developing time is decreased. This paper uses a currently used video codec as an anchor codec and develops a coding method including progressive scaling and a deep neural network to overcome low temporal correlation between frames of a PoHV. Since it is difficult to temporally predict a correlation between frames of a PoHV, this paper adopts a scaling function and a neural network in the encoding and decoding process, not adding complexity to an anchor itself to predict temporal correlation. The proposed coding method shows an enhanced coding gain of an average of 22%, compared with an anchor in all coding conditions. When observing numerical and optical reconstructions, the result images by the proposed show clearer objects and less juddering than the result by the anchor.

Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.

Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibition in PDAC have not been systematically explored. We performed a comprehensive pharmacological inhibition screen of the protein kinome and found that replication stress response (RSR) inhibitors were synthetically lethal with chloroquine (CQ) in PDAC cells. CQ treatment reduced de novo nucleotide biosynthesis and induced replication stress. We found that CQ treatment caused mitochondrial dysfunction and depletion of aspartate, an essential precursor for de novo nucleotide synthesis, as an underlying mechanism. Supplementation with aspartate partially rescued the phenotypes induced by CQ. The synergy of CQ and the RSR inhibitor VE-822 was comprehensively validated in both 2D and 3D cultures of PDAC cell lines, a heterotypic spheroid culture with cancer-associated fibroblasts, and in vivo xenograft and syngeneic PDAC mouse models. These results indicate a codependency on functional lysosomes and RSR in PDAC and support the translational potential of the combination of CQ and RSR inhibitors.

3D Static Point Cloud Registration by Estimating Temporal Human Pose at Multiview.

This paper proposes a new technique for performing 3D static-point cloud registration after calibrating a multi-view RGB-D camera using a 3D (dimensional) joint set. Consistent feature points are required to calibrate a multi-view camera, and accurate feature points are necessary to obtain high-accuracy calibration results. In general, a special tool, such as a chessboard, is used to calibrate a multi-view camera. However, this paper uses joints on a human skeleton as feature points for calibrating a multi-view camera to perform calibration efficiently without special tools. We propose an RGB-D-based calibration algorithm that uses the joint coordinates of the 3D joint set obtained through pose estimation as feature points. Since human body information captured by the multi-view camera may be incomplete, a joint set predicted based on image information obtained through this may be incomplete. After efficiently integrating a plurality of incomplete joint sets into one joint set, multi-view cameras can be calibrated by using the combined joint set to obtain extrinsic matrices. To increase the accuracy of calibration, multiple joint sets are used for optimization through temporal iteration. We prove through experiments that it is possible to calibrate a multi-view camera using a large number of incomplete joint sets.

Dynamic Reconstruction and Mesh Compression of 4D Volumetric Model Using Correspondence-Based Deformation for Streaming Service.

A sequence of 3D models generated using volumetric capture has the advantage of retaining the characteristics of dynamic objects and scenes. However, in volumetric data, since 3D mesh and texture are synthesized for every frame, the mesh of every frame has a different shape, and the brightness and color quality of the texture is various. This paper proposes an algorithm to consistently create a mesh of 4D volumetric data using dynamic reconstruction. The proposed algorithm comprises remeshing, correspondence searching, and target frame reconstruction by key frame deformation. We make non-rigid deformation possible by applying the surface deformation method of the key frame. Finally, we propose a method of compressing the target frame using the target frame reconstructed using the key frame with error rates of up to 98.88% and at least 20.39% compared to previous studies. The experimental results show the proposed method's effectiveness by measuring the geometric error between the deformed key frame and the target frame. Further, by calculating the residual between two frames, the ratio of data transmitted is measured to show a compression performance of 18.48%.

Robust Estimation and Optimized Transmission of 3D Feature Points for Computer Vision on Mobile Communication Network.

Due to the amount of transmitted data and the security of personal or private information in wireless communication, there are cases where the information for a multimedia service should be directly transferred from the user's device to the cloud server without the captured original images. This paper proposes a new method to generate 3D (dimensional) keypoints based on a user's mobile device with a commercial RGB camera in a distributed computing environment such as a cloud server. The images are captured with a moving camera and 2D keypoints are extracted from them. After executing feature extraction between continuous frames, disparities are calculated between frames using the relationships between matched keypoints. The physical distance of the baseline is estimated by using the motion information of the camera, and the actual distance is calculated by using the calculated disparity and the estimated baseline. Finally, 3D keypoints are generated by adding the extracted 2D keypoints to the calculated distance. A keypoint-based scene change method is proposed as well. Due to the existing similarity between continuous frames captured from a camera, not all 3D keypoints are transferred and stored, only the new ones. Compared with the ground truth of the TUM dataset, the average error of the estimated 3D keypoints was measured as 5.98 mm, which shows that the proposed method has relatively good performance considering that it uses a commercial RGB camera on a mobile device. Furthermore, the transferred 3D keypoints were decreased to about 73.6%.

Tat-p27 Ameliorates Neuronal Damage Reducing α-Synuclein and Inflammatory Responses in Motor Neurons After Spinal Cord Ischemia.

p27Kip1 (p27) regulates the cell cycle by inhibiting G1 progression in cells. Several studies have shown conflicting results on the effects of p27 against cell death in various insults. In the present study, we examined the neuroprotective effects of p27 against H2O2-induced oxidative stress in NSC34 cells and against spinal cord ischemia-induced neuronal damage in rabbits. To promote delivery into NSC34 cells and motor neurons in the spinal cord, Tat-p27 fusion protein and its control protein (Control-p27) were synthesized with or without Tat peptide, respectively. Tat-p27, but not Control-27, was efficiently introduced into NSC34 cells in a concentration- and time-dependent manner, and the protein was detected in the cytoplasm. Tat-p27 showed neuroprotective effects against oxidative stress induced by H2O2 treatment and reduced the formation of reactive oxygen species, DNA fragmentation, and lipid peroxidation in NSC34 cells. Tat-p27, but not Control-p27, ameliorated ischemia-induced neurological deficits and cell damage in the rabbit spinal cord. In addition, Tat-p27 treatment reduced the expression of α-synuclein, activation of microglia, and release of pro-inflammatory cytokines such as interleukin-1ß and tumor necrosis factor-α in the spinal cord. Taken together, these results suggest that Tat-p27 inhibits neuronal damage by decreasing oxidative stress, α-synuclein expression, and inflammatory responses after ischemia.

A Comparison of Pronator Quadratus Preservation and Dissection Approaches for Volar Plating of Comminuted Intra-articular Distal Radius Fracture.

PURPOSE: Although the pronator quadratus (PQ) preservation approach for volar plating of distal radius fracture has been commonly used recently, its superiority to the conventional PQ dissection approach, especially for comminuted intra-articular distal radius fractures, has not been well established. The purpose of this study was to assess the efficacy of PQ preservation for comminuted intra-articular fractures and to evaluate the healed PQ during hardware removal surgery. MATERIALS AND METHODS: From January 2014 to March 2019, 86 patients who underwent both volar plating for AO Foundation/Orthopedic Trauma Association classification type C2 or C3 distal radius fractures and subsequent hardware removal were assessed in this study. Radiographic measurements, clinical outcomes at each follow-up, and the integrity of healed PQ during hardware removal were compared between the PQ dissection (group D) and PQ preservation (group P) groups. RESULTS: Complete union with acceptable reduction on radiographic measurements was achieved in both groups. Group P showed a statistically significant earlier recovery of clinical outcomes at 2 weeks and 1 month postoperatively and improved anatomical restoration of PQ muscle covering the plate, which was identified during hardware removal surgery. Flexor tendon rupture was identified in 2 patients (5%) and tenosynovitis in 6 patients (14%) in group D; no patient had flexor tendon rupture (0%), and 2 patients (5%) had tenosynovitis in group P. CONCLUSIONS: Pronator quadratus preservation approach for volar plating is easily applicable and useful even for comminuted intra-articular distal radius fractures and is helpful for earlier restoration of wrist function and in preventing flexor tendon problems in the latter postoperative period.

Digital Hologram Watermarking Based on Multiple Deep Neural Networks Training Reconstruction and Attack.

This paper proposes a method to embed and extract a watermark on a digital hologram using a deep neural network. The entire algorithm for watermarking digital holograms consists of three sub-networks. For the robustness of watermarking, an attack simulation is inserted inside the deep neural network. By including attack simulation and holographic reconstruction in the network, the deep neural network for watermarking can simultaneously train invisibility and robustness. We propose a network training method using hologram and reconstruction. After training the proposed network, we analyze the robustness of each attack and perform re-training according to this result to propose a method to improve the robustness. We quantitatively evaluate the results of robustness against various attacks and show the reliability of the proposed technique.

Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs.

BACKGROUND: Pyridoxine (PDX; vitamin B6), is an essential vitamin. PDX deficiency induces various symptoms, and when PDX is misused it acts as a neurotoxicant, inducing severe sensory neuropathy. RESULTS: To assess the possibility of creating a reversible sensory neuropathy model using dogs, 150 mg/kg of PDX was injected subcutaneously into dogs for 7 days and body weight measurements, postural reaction assessments, and electrophysiological recordings were obtained. In addition, the morphology of dorsal root ganglia (DRG) and changes in glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were assessed at 1 day, 1 week, and 4 weeks after the last PDX treatment. During the administration period, body weight and proprioceptive losses occurred. One day after the last PDX treatment, electrophysiological recordings showed the absence of the H-reflex in the treated dogs. These phenomena persisted over the four post-treatment weeks, with the exception of body weight which recovered to the pre-treatment level. Staining (CV and HE) results revealed significant losses of large-sized neurons in the DRG at 1 day and 1 week after PDX treatment cessation, but the losses were recovered at 4 weeks post-treatment. The Iba-1 and GFAP immunohistochemistry results showed pronounced increases in reactive microglia/macrophage and satellite glial cell at 1 day and 1 week, respectively, after the last PDX treatment, and thereafter, immunoreactivity decreased with increasing time after PDX treatment. CONCLUSIONS: The results suggest that PDX-induced neuropathy is reversible in dogs; thus, dogs can be considered a good experimental model for research on neuropathy.

Ischemia-related changes of fat-mass and obesity-associated protein expression in the gerbil hippocampus.

Fat-mass and obesity-associated protein (Fto) plays important roles in energy metabolism. It also acts as a demethylase and is most abundantly found in the brain. In the present study, we examined the spatial and temporal changes of Fto immunoreactivity after five minutes of transient forebrain ischemia in the hippocampus. In the control group, Fto immunoreactivity was mainly observed in the nucleus of pyramidal cells in the CA1 and CA3 regions as well as the polymorphic layer, granule cell layer, and subgranular zone of the dentate gyrus. Fto immunoreactivity was transiently, but not significantly, increased in the hippocampal CA3 region and the dentate gyrus two days after ischemia compared to mice without ischemia in the sham-operated group. Four days after ischemia, low Fto immunoreactivity was observed in the stratum pyramidale of the CA1 region because of neuronal death, but Fto immunoreactive cells were abundantly detected in the stratum pyramidale of the CA3 region, which is relatively resistant to ischemic damage. Thereafter, Fto immunoreactivity progressively decreased in the hippocampal CA1 and CA3 regions and the dentate gyrus until ten days after ischemia. At this time-point, Fto immunoreactivity was significantly lower in the hippocampal CA1 and CA3 regions and the dentate gyrus compared to that in the sham-operated group. The reduction of Fto immunoreactive structures in the hippocampus may be associated with impairments in Fto-related hippocampal function.

Physical Stress Induced Reduction of Proliferating Cells and Differentiated Neuroblasts Is Ameliorated by Fermented Laminaria japonica Extract Treatment.

Laminaria japonica is widely cultivated in East Asia, including South Korea. Fucoidan, a main component of L. japonica, protects neurons from neurological disorders such as ischemia and traumatic brain injury. In the present study, we examined the effects of extract from fermented L. japonica on the reduction of proliferating cells and neuroblasts in mice that were physically (with electric food shock) or psychologically (with visual, auditory and olfactory sensation) stressed with the help of a communication box. Vehicle (distilled water) or fermented L. japonica extract (50 mg/kg) were orally administered to the mice once a day for 21 days. On the 19th day of the treatment, physical and psychological stress was induced by foot shock using a communication box and thereafter for three days. Plasma corticosterone levels were significantly increased after exposure to physical stress and decreased Ki67 positive proliferating cells and doublecortin immunoreactive neuroblasts. In addition, western blot analysis demonstrated that physical stress as well as psychological stress decreased the expression levels of brain-derived neurotrophic factor (BDNF) and the number of phosphorylated cAMP response element binding protein (pCREB) positive nuclei in the dentate gyrus. Fermentation of L. japonica extract significantly increased the contents of reduced sugar and phenolic compounds. Supplementation with fermented L. japonica extract significantly ameliorated the increases of plasma corticosterone revels and decline in the proliferating cells, neuroblasts, and expression of BDNF and pCREB in the physically stressed mice. These results indicate that fermented L. japonica extract has positive effects in ameliorating the physical stress induced reduction in neurogenesis by modulating BDNF and pCREB expression in the dentate gyrus.

YOLO-Based Simultaneous Target Detection and Classification in Automotive FMCW Radar Systems.

This paper proposes a method to simultaneously detect and classify objects by using a deep learning model, specifically you only look once (YOLO), with pre-processed automotive radar signals. In conventional methods, the detection and classification in automotive radar systems are conducted in two successive stages; however, in the proposed method, the two stages are combined into one. To verify the effectiveness of the proposed method, we applied it to the actual radar data measured using our automotive radar sensor. According to the results, our proposed method can simultaneously detect targets and classify them with over 90% accuracy. In addition, it shows better performance in terms of detection and classification, compared with conventional methods such as density-based spatial clustering of applications with noise or the support vector machine. Moreover, the proposed method especially exhibits better performance when detecting and classifying a vehicle with a long body.

P27 Protects Neurons from Ischemic Damage by Suppressing Oxidative Stress and Increasing Autophagy in the Hippocampus.

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 µM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 µM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.

Phosphoglycerate Mutase 1 Prevents Neuronal Death from Ischemic Damage by Reducing Neuroinflammation in the Rabbit Spinal Cord.

Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that increases glycolytic flux in the brain. In the present study, we examined the effects of PGAM1 in conditions of oxidative stress and ischemic damage in motor neuron-like (NSC34) cells and the rabbit spinal cord. A Tat-PGAM1 fusion protein was prepared to allow easy crossing of the blood-brain barrier, and Control-PGAM1 was synthesized without the Tat peptide protein transduction domain. Intracellular delivery of Tat-PGAM1, not Control-PGAM1, was achieved in a time- and concentration-dependent manner. Immunofluorescent staining confirmed the intracellular expression of Tat-PGAM1 in NSC34 cells. Tat-PGAM1, but not Control-PGAM1, significantly alleviated H2O2-induced oxidative stress, neuronal death, mitogen-activated protein kinase, and apoptosis-inducing factor expression in NSC34 cells. After ischemia induction in the spinal cord, Tat-PGAM1 treatment significantly improved ischemia-induced neurological impairments and ameliorated neuronal cell death in the ventral horn of the spinal cord 72 h after ischemia. Tat-PGAM1 treatment significantly mitigated the ischemia-induced increase in malondialdehyde and 8-iso-prostaglandin F2α production in the spinal cord. In addition, Tat-PGAM1, but not Control-PGAM1, significantly decreased microglial activation and secretion of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α induced by ischemia in the ventral horn of the spinal cord. These results suggest that Tat-PGAM1 can be used as a therapeutic agent to reduce spinal cord ischemia-induced neuronal damage by lowering the oxidative stress, microglial activation, and secretion of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α.

Pyridoxine Deficiency Exacerbates Neuronal Damage after Ischemia by Increasing Oxidative Stress and Reduces Proliferating Cells and Neuroblasts in the Gerbil Hippocampus.

We investigated the effects of pyridoxine deficiency on ischemic neuronal death in the hippocampus of gerbil (n = 5 per group). Serum pyridoxal 5'-phosphate levels were significantly decreased in Pyridoxine-deficient diet (PDD)-fed gerbils, while homocysteine levels were significantly increased in sham- and ischemia-operated gerbils. PDD-fed gerbil showed a reduction in neuronal nuclei (NeuN)-immunoreactive neurons in the medial part of the hippocampal CA1 region three days after. Reactive astrocytosis and microgliosis were found in PDD-fed gerbils, and transient ischemia caused the aggregation of activated microglia in the stratum pyramidale three days after ischemia. Lipid peroxidation was prominently increased in the hippocampus and was significantly higher in PDD-fed gerbils than in Control diet (CD)-fed gerbils after ischemia. In contrast, pyridoxine deficiency decreased the proliferating cells and neuroblasts in the dentate gyrus in sham- and ischemia-operated gerbils. Nuclear factor erythroid-2-related factor 2 (Nrf2) and brain-derived neurotrophic factor (BDNF) levels also significantly decreased in PDD-fed gerbils sham 24 h after ischemia. These results suggest that pyridoxine deficiency accelerates neuronal death by increasing serum homocysteine levels and lipid peroxidation, and by decreasing Nrf2 levels in the hippocampus. Additionally, it reduces the regenerated potentials in hippocampus by decreasing BDNF levels. Collectively, pyridoxine is an essential element in modulating cell death and hippocampal neurogenesis after ischemia.