Ultraviolet- and infrared-induced 11 beta-hydroxysteroid dehydrogenase type 1 activating skin photoaging is inhibited by red ginseng extract containing high concentration of ginsenoside Rg3(S).

BACKGROUND: Sun irradiation is one of major extrinsic stressors responsible for premature skin aging through activation and expression of 11 beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), which converts inactive cortisone to active cortisol. The aim of this study was to evaluate the inhibitory effects of red ginseng extract containing high concentrations of ginsenoside Rg3 (S) (GERg3) on 11ß-HSD1-induced skin photoaging. METHODS: To evaluate the inhibitory effects of GERg3 on ultraviolet- (UV) or infrared (IR)-induced skin photoaging, human dermal fibroblasts or a normal human 3D skin model was exposed to UV or an IR. RT-PCR, ELISA, Western blot, and H&E staining were used for evaluations. GERg3 was isolated from crude red ginseng. RESULTS: GERg3 inhibited the increased expressions of 11ß-HSD1, interleukin (IL)-6, and matrix metalloproteinase-1 (MMP-1) in UVB- or IR-exposed Hs68 cells. Additionally, the increased cortisol, IL-6, and MMP-1 expressions were effectively reduced by GERg3 in UVA-exposed 3D skin models. The photoinduced decrease in type 1 procollagen also recovered as a result of GERg3 treatment in Hs68 cells and the 3D skin model. In addition, the UVA-exposed dermal thickness was decreased in comparison with the UVA-protected 3D skin model, recovered with GERg3 treatment. CONCLUSION: GERg3 had antiphotoaging effects in UV- or IR-exposed human dermal fibroblasts and normal human 3D skin model.

Longitudinal FDG microPET imaging of neuropathic pain: does cerebellar activity correlate with neuropathic pain development in a rat model?

BACKGROUND: We used [F-18] FDG microPET imaging as part of a longitudinal study to investigate changes in the brain. METHODS: Glucose metabolism during the development of neuropathic pain after tibial and sural nerve transection (TST) model rats. MicroPET images were obtained 1 week before operation and then weekly for 8 weeks post-operation. RESULTS: The behavioral test was performed immediately after the every FDG administration. After TST modeling, neuropathic pain rats showed increased mechanical sensitivity of the injured hind paw. The withdrawal response to mechanical pain stimulation by von Frey filaments was observed within the first week (3.8 ± 0.73), and it rapidly increased in the third week (7.13 ± 0.82). This response reached a peak in the fourth week after surgery (9.0 ± 0.53), which persisted until the eighth week. In microPET scan imaging, cerebellum, which initially started from the ansiform lobule, was activated gradually to all part from the third week in all image acquisitions through the eighth week. CONCLUSIONS: The longitudinal microPET scan study of brains from neuropathic pain rat models showed sequential cerebellar activity that was in accordance with results from behavioral test responses, thus supporting a role for the cerebellum in the development of neuropathic pain.

Performance of on-site pilot static granular bed reactor (SGBR) for treating dairy processing wastewater and chemical oxygen demand balance modeling under different operational conditions.

The performance and operational stability of a pilot-scale static granular bed reactor (SGBR) for the treatment of dairy processing wastewater were investigated under a wide range of organic and hydraulic loading rates and temperature conditions. The SGBR achieved average chemical oxygen demand (COD), biological oxygen demand (BOD), and total suspended solids (TSS)-removal efficiencies higher than 90% even at high loading rates up to 7.3 kg COD/m(3)/day, with an hydraulic retention time (HRT) of 9 h, and at low temperatures of 11 °C. The average methane yield of 0.26 L CH4/g COD(removed) was possibly affected by a high fraction of particulate COD and operation at low temperatures. The COD mass balance indicated that soluble COD was responsible for most of the methane production. The reactor showed the capacity of the methanogens to maintain their activity and withstand organic and hydraulic shock loads.

Septic wastewater treatment using recycled rubber particles as biofiltration media.

Performance of the laboratory-scale recycled rubber particles (RRP) biofilter was compared to a conventional gravel system and a peat biofilter for treatment of septic tank effluent. During the study, the RRP biofilter provided similar or better performance than other systems in terms of organic removal and hydraulic capacity. After the start-up period, RRP biofilter achieved removal efficiencies for BOD5, total suspended solids (TSS), ammonia nitrogen of 96%, 93%, and 90%, respectively, over the range of hydraulic loading rates of 57-204 L/m2/d. On the other hand, the peat biofilter failed hydraulically and the gravel system showed high TSS concentrations in the effluent. RRP provided high surface area and sufficient time for biological treatment. In addition, RRP was observed to provide ammonia adsorption capacity. The results showed that RRP has the potential to be used as substitutes for natural aggregate such as gravel in septic system drainfields. The RRP biofilter can be used as alternative septic systems for the sites where an existing septic system has failed or site conditions, such as high groundwater table or small lot size, are not suitable for the installation of conventional septic systems.

Evaluation of an on-site pilot static granular bed reactor (SGBR) for the treatment of slaughterhouse wastewater.

An on-site pilot-scale static granular bed reactor (SGBR) system was evaluated for treating wastewater from a slaughterhouse in Iowa. The study evaluated SGBR reactor suitability for slaughterhose wastewater having high particulate COD concentration (7.9 ± 4.3 g COD/L) at 0.3-1.4 m(3)/m(2)/day of the surface loading rates. High organic removal efficiency (over 95% of TSS and VSS removal) was obtained due to the consistent treatability of SGBR system during operation at HRTs of 48, 36, 30, 24, and 20 h. The average effluent TSS, VSS, COD, soluble COD, and BOD(5) concentrations were 84, 71, 301,197, and 87 mg/L, respectively. An effective backwash procedure was performed once every 7-14 days to waste a portion of the accumulated solids in the system. This procedure limited the increase in hydraulic head loss and maintained the system stability. COD removal efficiencies greater than 95% were achieved at organic loading rates ranging from 0.77 to 12.76 kg/m(3)/day.

Combined treatment of Taraxaci Herba and R7050 alleviates the symptoms of herpes simplex virus-induced Behçet's disease in rats.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory systemic disease that affects multiple organs. The causes of BD are still unknown, but it is primarily characterized by autoimmune reaction in the blood vessels. Current research focuses on treatments that can reduce the non-typical inflammatory responses of BD. Nevertheless, studies on improving the inflammatory effect of BD using inflammation mechanisms are still insufficient. Therefore, we conducted the integrated treatments related to inflammation modulation and achieved alleviation of symptoms in BD mice. METHODS: To understand the complex etiology of BD and compare its management, the herpes simplex virus (HSV)-induced BD mouse model was used. In order to alleviate the inflammatory response in BD mice, Taraxaci Herba (TH, herbal medicine), R7050-a TNFα inhibitor, and a mixture of TH and R7050 were injected for 2 weeks repetitively. The SCORAD index was examined to evaluate the cutaneous inflammations. In addition, histological changes and inflammatory factors were analyzed. RESULTS: Repetitive injection of TH and/or R7050 reduced the symptoms of BD and significantly decreased IL-6, IL-1ß, and TNFα in blood sera. Moreover, this treatment reduced the ulcers and the deterioration of skin. CONCLUSIONS: The results of our study showed that the down-regulation of inflammatory factors is related to the control of immune responses in BD models, suggesting that a mixed drug treatment may be more effective in improving the condition of BD.

Does work time limit for resident physician affect short-term treatment outcome and hospital length of stay in patients with spontaneous intracerebral hemorrhage?: a two-year experience at a single training hospital in South Korea.

OBJECTIVE: To compare short-term treatment outcomes at hospital discharge and hospital length of stay (LOS) in patients with spontaneous intracerebral hemorrhage (sICH) before and after introduction of resident physician work time limit (WTL). METHODS: We retrospectively reviewed consecutive patients treated for sICH at our institution between 2016 and 2019. Then we dichotomized these patients into two groups, pre-WTL and post-WTL. We analyzed demographic elements and clinical features, and hospital length of stay (LOS). We evaluated short-term outcome using modified Rankin scale score at hospital discharge and then divided it into "good" and "poor" outcome groups. We subsequently, compared short-term treatment outcome and hospital LOS between the pre-WTL and post-WTL groups. RESULTS: Out of 779 patients, 420 patients (53.9%) were included in the pre-WTL group, and 359 (46.1%) in post-WTL. The mortality rate in sICH patients was higher in the post-WTL group (pre-WTL; 13.6% vs. post-WTL; 17.3%), but there was no statistically significant difference in short-term outcome including mortality (p=0.332) between the groups. The LOS also, was not significantly different between the two groups (pre-WTL; 19.0 days vs. post-WTL; 20.2 days) (p=0.341). The initial Glasgow Coma Scale score, personal stroke history, and mean age were the only independent outcome predicting factors for patients with sICH. CONCLUSIONS: Some neurosurgeons may expect poorer outcome for sICH after implementation of the WTL of the K-MHW for resident physician however, enforcement of the WTL did not significantly influence the short-term outcome and hospital LOS for sICH in our hospital. Further well-designed multi-institutional prospective studies on the effects of WTL in sICH patient outcome, are anticipated.

Differential activation of face memory encoding tasks in alcohol-dependent patients compared to healthy subjects: an fMRI study.

It has been hypothesized that the right hemisphere of the brain is more sensitive to alcohol-related damage than the left hemisphere. The present study tested this hypothesis, using functional MRI to determine whether the pattern for right hemispheric activity is different for alcohol-dependent patients, compared to normal healthy individuals. Two different types of memory encoding tasks were performed separately: word and face encoding for both alcohol-dependent patients and normal healthy volunteers. The data for the normal volunteers indicate that the left prefrontal region is more active during word encoding, whereas the right parahippocampal region is more active during face encoding. The results for the patient data, however, demonstrated left lateralization in the prefrontal area during word encoding, while right lateralization in the parahippocampal region during face encoding was not observed. Therefore, alcoholism appears to have no influence on left hemispheric activity, since the activation pattern was similar to that observed for normal healthy persons. However, the absence of right hemispheric lateralization in alcohol-dependent patients is consistent with the hypothesis that the right hemisphere is more vulnerable to alcohol-related damage than the left hemisphere.

Comprehensive Hand Repetitive Intensive Strengthening Training (CHRIST)-induced morphological changes in muscle size and associated motor improvement in a child with cerebral palsy: an experimenter-blind study.

PURPOSE: This case study was conducted to determine Comprehensive Hand Repetitive Intensive Strengthening Training (CHRIST)-induced morphological changes in the commonly affected extensor carpi radialis (ECR) and triceps brachii (TRI) muscle and associated muscle strength and motor performance in a child with hemiparetic cerebral palsy (CP) using standardized clinical tests and ultrasound imaging. DESIGN: A single case study with pre-/post-test. SUBJECT: A 4.9-year-old female, diagnosed with hemiparetic CP. METHOD: The child received a 5-week course of CHRIST course, comprising of 60-minute periods a day, five times a week. A real-time ultrasound imaging was performed to determine the CHRIST-induced changes in cross-sectional area (CSA) of the ECR and TRI. Clinical tests including the modified Wolf Motor function test (WMFT), the modified Jebsen-taylor hand function test (Jebsen hand) and the modified Pediatric Motor Activity Log (PMAL) questionnaire were used to compare the intervention-related changes in motor performance in upper extremity. RESULTS: Ultrasound imaging data showed that the CSAs of both ECR and TRI muscles of the affected upper limb at relaxation and contraction states were enhanced and these therapy-induced morphological changes were associated with enhanced muscle strength and gross motor performance in reaching and grasping skills. CONCLUSIONS: Our results suggest that the CHRIST is effective in treating muscle weakness and motor function in a child with hemiparetic CP. This is the first evidence in literature that might shed light on the therapeutic efficacy of our novel intervention on muscle size, associated muscle strength and motor improvement.

Structural and Functional Alterations at Pre-Epileptic Stage Are Closely Associated with Epileptogenesis in Pilocarpine-induced Epilepsy Model.

Pilocarpine-induced rat epilepsy model is an established animal model that mimics medial temporal lobe epilepsy in humans. The purpose of this study was to investigate neuroimaging abnormalities in various stages of epileptogenesis and to correlate them with seizure severity in pilocarpine-induced rat epilepsy model. Fifty male Sprague-Dawley rats were subject to continuous video and electroencephalographic monitoring after inducing status epilepticus (SE) and seizure severity was estimated by frequency and total durations of class 3 to 5 spontaneous recurrent seizures (SRS) by modified Racine's classification. The 7.0 Tesla magnetic resonance imaging (MRI) with high resolution flurodeoxyglucose positron emission tomography (FDG-PET) was performed at 3 hours, 1, 3, 7 days and 4 weeks after the initial insult. The initial SRS was observed 9.7±1.3 days after the pilocarpine injection. MRI revealed an abnormal T2 signal change with swelling in both hippocampi and amygdala in acute (day 1 after injection) and latent phases (days 3 and 7), in association with PET hypometabolism in these areas. Interestingly, the mean frequency of class 3 to 5 SRS was positively correlated with abnormal T2 signals in hippocampal area at 3 days. SRS duration became longer with more decreased glucose metabolism in both hippocampi and amygdala at 7 days after pilocarpine injection. This study indicates that development and severity of SRS at chronic phase could be closely related with structural and functional changes in hippocampus during the latent period, a pre-epileptic stage.

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

PURPOSE: Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. MATERIALS AND METHODS: We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹8F-2-fluoro-2-deoxyglucose positron emission tomography. RESULTS: During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. CONCLUSION: Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Therapeutic potentials of human adipose-derived stem cells on the mouse model of Parkinson's disease.

The treatment of Parkinson's disease (PD) using stem cells has long been the focus of many researchers, but the ideal therapeutic strategy has not yet been developed. The consistency and high reliability of the experimental results confirmed by animal models are considered to be a critical factor in the stability of stem cell transplantation for PD. Therefore, the aim of this study was to investigate the preventive and therapeutic potential of human adipose-derived stem cells (hASC) for PD and was to identify the related factors to this therapeutic effect. The hASC were intravenously injected into the tail vein of a PD mouse model induced by 6-hydroxydopamine. Consequently, the behavioral performances were significantly improved at 3 weeks after the injection of hASC. Additionally, dopaminergic neurons were rescued, the number of structure-modified mitochondria was decreased, and mitochondrial complex I activity was restored in the brains of the hASC-injected PD mouse model. Overall, this study underscores that intravenously transplanted hASC may have therapeutic potential for PD by recovering mitochondrial functions.

[Effects of Silver-Care-Robot Program on Cognitive Function, Depression, and Activities of Daily Living for Institutionalized Elderly People].

PURPOSE: The purpose of this study was to identify the effects on cognitive function, depression, and activities of daily living of Silver-Care-Robot Program for institutionalized elders. METHODS: This study was a nonequivalent control group pretest-posttest design. The participants were 42 institutionalized elders (17 in the experimental group and 25 in the control group). The Silver-Care-Robot Program was provided as an intervention which was conducted twice a week for 5 weeks. The Silver-Care-Robot Program is an integrated entertainment program to help the mental, emotional, and physical health of elderly people. Pre-test was conducted on the two groups, and, in order to examine the effects of intervention, a post-test was conducted after 5 weeks. RESULTS: There were significant differences in cognitive function and ADL (activities of daily living) between two groups after the program. But the difference in depression in the institutionalized elders was not statistically significant between the two groups. CONCLUSION: The Silver-Care-Robot Program should be considered as a regular program for cognitive function and activities of daily living for institutionalized elders.

Activation of selective transcription factors and cytokines by water-soluble extract from Lentinus lepideus.

We isolated a water-soluble extract, PG101, from cultured mycelia of Lentinus lepideus. Treatment of human peripheral blood mononuclear cells (PBMCs) with PG101 increased levels of TNF-alpha, IL-1beta, IL-10, and IL-12 by 100- to 1000-fold, whereas GM-CSF and IL-18 were activated by an order of magnitude. On the contrary, IFN-gamma and IL-4 were not affected. The response to PG101 occurred in a dose- and time-dependent manner. From the human PBMCs treated with PG101, TNF-alpha was a first cytokine to be activated, detectable at 2 hr post-treatment followed by IL-1beta at 6 hr post-treatment. IL-12 and IL-10 were the next to follow. GM-CSF and IL-18 both showed significant increases 24 hr after treatment. When PBMCs were sorted into various cell types, monocyte/macrophages, but not T and B cells, were the major target cell type responsive to PG101. Consistent with this result, the profile of cytokine expression upon PG101 treatment was comparable between PBMCs and a human promonocytic cell line (U937), whereas cell lines of T cell and myeloid origins did not respond to PG101. Data from a transient transfection assay involving specific reporter plasmids indicated that cellular transcription factor such as NF-kappaB, but not AP-1, was highly activated by PG101. Results from a gel retardation assay and the experiment involving a specific NF-kappaB inhibitor confirmed the involvement of NF-kappaB. Despite its significant biological effect on various cytokines, PG101 remained nontoxic in both rats and PBMCs even at a biological concentration approximately 20 times greater. PG101 demonstrates great potential as a therapeutic immune modulator.

Crystallization and preliminary X-ray analysis of class II fructose-1,6-bisphosphate aldolase from Thermus caldophilus.

In this study, we have crystallized class II fructose-1,6-bisphosphate aldolase (FBA) from Thermus caldophilus (Tca). Purified Tca FBA is a tetrameric enzyme of 305 residues, which crystallizes in the space group P2(1)2(1)2(1) (cell dimensions a = 98.9, b = 113.1, c = 115.7 A), with four molecules in the asymmetric unit. A complete diffraction data set was obtained from orthorhombic crystals at resolution of 2.2 A.

Rg3-enriched Korean Red Ginseng improves vascular function in spontaneously hypertensive rats.

BACKGROUND: Panax ginseng has distinct and impressive health benefits, such as improved blood pressure and immune system functioning. Rg3-enriched Korean Red Ginseng (REKRG) isolated from Korean Red Ginseng contains a high percentage of Rg3. METHODS: In this study, we examined the effects of REKRG on endothelial cell nitric oxide synthase (eNOS) activation and adhesion molecules in endothelial cells and vascular function in rats. RESULTS: REKRG dose-dependently increased eNOS phosphorylation and nitric oxide (NO) production in endothelial cells. In addition, REKRG markedly inhibited the tumor necrosis factor-α (TNF-α)-mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent vasorelaxation in the Wistar-Kyoto (WKY) rat and spontaneously hypertensive rats (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased serum NO levels and reduced the mean aortic intima-media thickness compared with controls. CONCLUSION: Taken together, these results suggest that REKRG increased vascular function and improved immune system functioning. Therefore, REKRG is a very useful food for preventing or improving various cardiovascular diseases.

Auditory adaptation to sound intensity in conscious rats: 2-[F-18]-fluoro-2-deoxy-D-glucose PET study.

Despite the importance of the adaptive process for discriminating the broad range of sound intensity, there have been few systemic investigations targeting the auditory mechanisms. In this study, the adaptation effect of sound intensity on the change in glucose metabolism in rat brains was examined using a PET technique. In the first experiment, broadband white noise sound (40, 60, 80, or 100 dB sound pressure level) was given for 30 min after an 2-[F-18]-fluoro-2-deoxy-D-glucose injection in an awake condition. In the second experiment, sound stimuli with an intensity modulation of 0, 0.5, and 5.0 Hz in frequency and at three intensity levels were used for examining the metabolism change according to the short time scale variation of the sound intensity. As a result, the metabolic activities in the bilateral cochlear nucleus, superior olivary complexes, and inferior colliculus were proportional to the sound intensity level, whereas the bilateral auditory cortical areas unexpectedly decreased as the sound intensity level increased in the first experiment. In the second experiment, the glucose metabolism in the auditory cortex was higher at 0.5 and 5.0 Hz modulation frequency than the 0.0 Hz modulation frequency, while retaining an inverse relationship with the sound intensity. The metabolism in inferior colliculus was higher at 5.0 Hz modulation frequency than 0.0 and 0.5 Hz modulation frequencies. Taken together, the auditory cortex metabolism seemed to be actively adapted to the average sound intensity, which indicates that it plays an important role in processing the broad range to sound intensity more than the other nucleus of the auditory pathway. Especially, this study demonstrated that the sound intensity-dependent glucose metabolism can be seen in a small rodent's brain stem level using 2-[F-18]-fluoro-2-deoxy-D-glucose PET functional neuroimaging.

Analgesic mechanism of electroacupuncture in an arthritic pain model of rats: a neurotransmitter study.

PURPOSE: We investigated what kinds of neurotransmitters are related with electroacupuncture (EA) analgesia in an arthritic pain model of rats. MATERIALS AND METHODS: One hundred rats were assigned to six groups: control, EA, opioid, adrenergic, serotonin and dopamine group. A standardized model of inflammatory arthritis was produced by injecting 2% carrageenan into the knee joint cavity. EA was applied to an acupoint for 30 min in all groups except fo the control group. In the opioid, adrenergic, serotonin and dopamine groups, each receptor antagonist was injected intraperitoneally to their respective group before initiating EA. RESULTS: In the opioid receptor antagonist group, adrenergic receptor antagonist group, serotonin receptor antagonist group, dopamine receptor antagonist group and the control group weight-bearing force decreased significantly from 30 min to 180 min after EA in comparison with the EA group. CONCLUSION: The analgesic effects of EA are related to opioid, adrenergic, serotonin and dopamine receptors in an arthritic pain model of rats.

The effect of robo-horseback riding therapy on spinal alignment and associated muscle size in MRI for a child with neuromuscular scoliosis: an experimenter-blind study.

PURPOSE: This case study was conducted to highlight the clinical and radiological features of a patient with progressive neuromuscular scoliosis before and after robo-horseback riding therapy (HBRT). DESIGN: A clinical, laboratory, and radiological analysis of a single case. SUBJECT: An 11-year-old child, dignosed right thoracolumbar neuromuscular scoliosis secondary to cerebral palsy. METHOD: The child received a 5-week course of robo-HBRT, comprising of 60-minute periods a day, five times a week. Postural alignment was determined by Cobb's method. A real-time magnetic resonance imaging (MRI) was performed to determine the robo-HBRT-induced changes in cross-sectional area (CSA) of bilateral thoracic (T2) and lumbar (L2) paraspinalis. Clinical tests including the standard Gross Motor Function Measure (GMFM) and manual muscle testing (MMT) with the Lafayette Manual Muscle Tester were used to compare the intervention-related changes in motor performance and power. The surface EMG was also used to examine therapy-induced changes in muscle activity amplitude for bilateral T2 and L2 paraspinalis and rectus abdominis muscles. RESULTS: Clinical motor and strength scores increased after the intervention. Radiographic Cobb's angle, MRI, and electromyographic amplitude data demonstrated notably enhanced spinal alignment and muscle fiber CSA and symmetry, respectively. CONCLUSIONS: This is the first study to provide evidence of the therapeutic efficacy of a novel form of robo-HBRT on motor function and associated structural and motor control improvements, thus suggesting a method of augmenting therapy in neuromuscular scoliosis.

Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys.

Intracerebroventricular injection of streptozotocin (icv-STZ) in rodents induces cellular and behavioral features mimicking Alzheimer's disease (AD). However, the effect of icv-STZ in terms of regional cerebral glucose metabolism has not yet been examined in vivo. Given that regionally specific hypometabolism of glucose is a consistent neuroimaging marker in early AD, we monitored 18F-deoxyglucose uptake using a high-resolution micro-PET after icv-STZ in non-human primates. Two cynomolgus monkeys (Macaca fascicularis) received STZ (2 mg/kg), and another two were given normal saline as controls, at the cerebellomedullary cistern (CM) three times (day 1, 7, and 14). FDG-PET, as well as MRI for structural evaluation, was performed immediately before, six weeks after, and 12 weeks after the first icv injection. In the STZ group, FDG uptake decreased significantly in comparison to the pre-injection baseline, at the precuneus, the posterior cingulate, and medial temporal cortices. Increase in sulcal markings suggesting brain atrophy was observed by MRI at six weeks post-injection. The structural changes normalized at 12 weeks, but the reduced FDG uptake persisted at the same loci. The cortical distribution of glucose hypometabolism was similar to that at early stages of AD patients. The findings demonstrate that the effect of icv-STZ is regionally specific, lending further support for the method as a model of AD pathogenesis.