Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective ser...Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.展开更多
Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system.In brain research,a series of powerful and novel gene editing technologi...Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system.In brain research,a series of powerful and novel gene editing technologies are based on these systems.Although many viral vectors are used in rodents,their full application has been limited in non-human primates.To identify viral vectors that can stably and effectively express exogenous genes within nonhuman primates,eleven commonly used recombinant adeno-associated viral and lentiviral vectors,each carrying a gene to express green or red fluorescence,were injected into the parietal cortex of four rhesus monkeys.The expression of fluorescent cells was used to quantify transfection efficiency.Histological results revealed that recombinant adeno-associated viral vectors,especially the serotype 2/9 coupled with the cytomegalovirus,human synapsin I,or Ca2+/calmodulin-dependentproteinkinaseII promoters,and lentiviral vector coupled with the human ubiquitin C promoter,induced higher expression of fluorescent cells,representing high transfection efficiency.This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates(NHPs).These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.展开更多
Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells.Therefore,neural stem cell transplantation can be used to promote functional recovery of the nervous system.Rhesus monkey neu...Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells.Therefore,neural stem cell transplantation can be used to promote functional recovery of the nervous system.Rhesus monkey neural stem cells(1×105 cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions.Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well.Transplanted cells were detected at the lesion site,but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum.Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall,and integrated into the recipient brain.Behavioral tests revealed that spatial learning and memory ability improved,indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.展开更多
BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotectiv...BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed. OBJECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University. MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3) and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co.Ltd, Wuhan); 12 800 dots chip (Boxing Company, Shanghai). METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created. ② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW image analysis software. Morphological change of corpora striata of operative side was observed in the rhesus monkeys between two groups. Total RNA was extracted from cerebral tissue. ③ Detection of gene chip: Cy3-duTP and Cy5-duTP were used to respectively perform reverse transcription labeling. The sample was reversely transcribed into cDNA, then hybridized with cDNA of cerebral tissue. Genes with the separate absolute value of cy3 and cy5>800, cy3/cy5 > 2(high expression) or < 0.5 (low expression) were found out. Those were genes with differential expression. ④ The expressions of IGF-1 mRNA and protein level of corpora striata in ischemic side of rhesus monkeys were detected between sham operation group and ischemia/reperfusion group at 9 and 24 hours after ischemia/reperfusion with in situ hybridization method and immunohistochemical method. Brown granules were IGF-1 protein positive cells. ⑤ Analysis of variance was used in the difference comparison of measurement data among groups. MAIN OUTCOME MEASURES: ① Change of morphological structure of corpora striata at ischemic side in rhesus monkeys. ② Change of cerebral gene expression profiles at ischemia/reperfusion in rhesus monkeys between two groups. ③ Expression of IGF-1 mRNA and protein level of corpora striata at ischemia/reperfusion in rhesus monkeys between two groups. RESULTS: ① Pathological change : Obvious pathological change of cerebral infarction appeared in the ischemia and reperfusion group, while there was no such pathological change in the sham operation group. ② Change of gene expression profile : There were 4480 genes with difference expression in the ischemia/reperfusion group and sham-operation group, in which, 260 genes had high expression and their absolute value was over 800, and 63 genes had low expression. cy3/cy5 of IGF-1 was 0.379, being relative low expression. ③ IGF-1 mRNA and protein positive cell counts in corpora striata at cerebral ischemic side[IGF-1 mRNA:(9.72±1.18),(9.11±0.76),(14.77±0.60) counts/field;IGF-1 protein:(15.11±1.83),(15.39±0.78),(34.62±0.97)counts/field,P < 0.05-0.01]. CONCLUSION: IGF-1 mRNA and protein are lowly expressed in middle cerebral artery of rhesus monkeys at ischemia/reperfusion.展开更多
A recent study by researchers at the Kunming Institute of Zoology (KIZ) of the Chinese Academy of Sciences (CAS) identifies the albinism gene of rhesus monkeys using the method of molecular technology, and suggests th...A recent study by researchers at the Kunming Institute of Zoology (KIZ) of the Chinese Academy of Sciences (CAS) identifies the albinism gene of rhesus monkeys using the method of molecular technology, and suggests the age of the albinism gene in rhesus monkeys should be roughly 800,000 years. The general albinism展开更多
AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neona...AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.展开更多
AIM:In order to improve the biocompatibility of intraocular lenses(IOL),the polymethylmethacrylate(PMMA)IOL was modified with F-heparin. METHODS:The PMMA IOL was modified with F ions and heparin by the technique of io...AIM:In order to improve the biocompatibility of intraocular lenses(IOL),the polymethylmethacrylate(PMMA)IOL was modified with F-heparin. METHODS:The PMMA IOL was modified with F ions and heparin by the technique of ion beam combined with low temperature and low pressure plasma.The monkeys(20 eyes)with cataract partly were randomly classified into 2 groups and implanted with PMMA IOL and modified IOL respectively for 180 days.All of the eyes were examined by slit-lamp microscope at postoperative 15,30,60,90,180 days.The extracted IOL was analyzed with computer image analysis,light microscope(LM)and scanning electron microscope(SEM)at postoperative 180 days. RESULTS:The early inflammatory reactions postoperatively include anterior chamber exudation and aqueous cell count. The modified IOL group showed less than the non-modified IOL group.The late foreign body cell reaction that adhered to the surface of non-modified IOL was more predominant.The morphologic and pathological changes of posterior capsule opacification(PCO)in monkeys’ eyes included fibrosis-type, pearl-type and soemmerring’s ring.There was a significant difference between the two groups. CONCLUSION:F-heparin modified IOL has good uveal and capsular biocompatibility.展开更多
DEAR EDITOR,Major depressive disorder (MDD), commonly known as depression, is a mental disease characterized by a core symptom of low mood. It lasts at least two weeks (Badamasi et al., 2019;Wang et al., 2019) and is ...DEAR EDITOR,Major depressive disorder (MDD), commonly known as depression, is a mental disease characterized by a core symptom of low mood. It lasts at least two weeks (Badamasi et al., 2019;Wang et al., 2019) and is frequently accompanied by low self-esteem, loss of interest in routinely enjoyable activities, low energy, and unexplained pain (Huey et al., 2018;Park et al., 2012;Post & Warden, 2018;Rice et al., 2019;Xiao et al., 2018). Approximately 2%–8% of adults with MDD commit suicide (Richards & O'Hara, 2014;Strakowski & Nelson, 2015), and around half of suicidal individuals suffer depression or other mood disorders (Bachmann, 2018).展开更多
Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments...Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).展开更多
Taihang Mountain area, a high Incidence area of human esophageal cancer in Northern China. 124 Rhesus monkeys (Macacs Mulatta) were caught in the area in January 1989. Among them, two monkeys died of esophageal carcin...Taihang Mountain area, a high Incidence area of human esophageal cancer in Northern China. 124 Rhesus monkeys (Macacs Mulatta) were caught in the area in January 1989. Among them, two monkeys died of esophageal carcinoma in 1990. Case 1, a male monkey about 6. 5 yean old and weighing 14. 5 kg, had symptoms of salivation, vomiting and dysphagia in Fabruary 1990. The symptoms became gradually more serious and died in march 1990. Postmortem examination revealed a huge tumor in the distal segment of esophagus, causing severe structure of the organ. The tumor was classified as medullary type and histopathologically diagnosed as a well differentiated squamous cell carcinoma, with metastases to mediastinum and lymph nodes of right gastric group. Case 2, a female monkey ablut 11-year-old and weighing 10. 0 kg, showed loss of appetite, tiredness, somnolence, caughing and vomiting in September and died in December 1990. Autopsy revealed an annular tumor involving the whole clcumference of lower portion of the展开更多
BACKGROUND:Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes.Testing in nonhuman primate models is necessary before clin...BACKGROUND:Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes.Testing in nonhuman primate models is necessary before clinical application in humans.Intraportal islet transplantation in monkeys is usually performed by surgical infusion during laparotomy or laparoscopy.In this paper,we describe a new method of percutaneous transhepatic portal catheterization(PTPC) as an alternative to current methods of islet transplantation in rhesus monkeys.METHODS:We performed ultrasound-guided PTPC in five adult rhesus monkeys weighing 7-8 kg,with portal vein catheterization confirmed by digital subtraction angiography.We monitored for complications in the thoracic and abdominal cavity.To evaluate the safety of ultrasound-guided PTPC,we recorded the changes in portal pressure throughout the microbead transplantation procedure.RESULTS:Ultrasound-guided PTPC and infusion of 16 000 microbeads/kg body weight into the portal vein was successful in all five monkeys.Differences in the hepatobiliary anatomy of rhesus monkeys compared to humans led to a higher initial complication rate.The first monkey died of abdominal hemorrhage 10 hours post-transplantation.The second suffered from a mild pneumothorax but recovered fully after taking only conservative measures.After gaining experience with the first two monkeys,we decreased both the hepatic puncture time and the number of puncture attempts required,with the remaining three monkeys experiencing no complications.Portal pressures initially increased proportional to the number of transplanted microbeads but returned to preinfusion levels at 30 minutes post-transplantation.The changes in portal pressures occurring during the procedure were not significantly different.CONCLUSIONS:Ultrasound-guided PTPC is an effective,convenient,and minimally invasive method suitable for use in non-human primate models of islet cell transplantation provided that care is taken with hepatic puncture.Its advantages must be weighed against the risks of procedure-related complications.展开更多
In the present research,two Chinese rhesus monkeys were inoculated intravenously with 5000 TCID50 of SIVmac239. The changes in the numbers of CD4+ T lymphocyte in peripheral blood,plasma viral loads,proviral DNA and h...In the present research,two Chinese rhesus monkeys were inoculated intravenously with 5000 TCID50 of SIVmac239. The changes in the numbers of CD4+ T lymphocyte in peripheral blood,plasma viral loads,proviral DNA and humoral antibodies against virus were periodically monitored during 121 days. At the early stage of infection,proviral DNA had been detected in PBMCs,and infectious SIVmac239 virus had been isolated from PBMCs. At the same period,the numbers of CD4+ T lymphocytes were significantly decreased,and maintained at low level during the 121-day period of infection. Plasma viral loads reached the peak at week 2 post-inoculation and kept at a steady state subsequently. Moreover,antibodies against viral proteins were detected from plasma. All the results showed that the two Chinese rhesus monkeys had been infected with SIVmac239 successfully. This animal model can be applied for further AIDS researches.展开更多
Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically,both in terms of branching a single trunk and in connecting multiple br...Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically,both in terms of branching a single trunk and in connecting multiple branches of an extratemporal segment.However,in the clinical treatment of facial nerve defects,allogeneic donors are limited.In this experiment,we exposed the left trunk and multiple branches of the extratemporal segment in six rhesus monkeys and dissected a gap of 25 mm to construct a monkey model of a whole left nerve defect.Six monkeys were randomly assigned to an autograft group or a xenogeneic acellular nerve graft group.In the autograft group,the 25-mm whole facial nerve defect was immediately bridged using an autogenous ipsilateral great auricular nerve,and in the xenogeneic acellular nerve graft group,this was done using a xenogeneic acellular nerve graft with trunk-branches.Examinations of facial symmetry,nerve-muscle electrophysiology,retrograde transport of labeled neuronal tracers,and morphology of the regenerated nerve and target muscle at 8 months postoperatively showed that the faces of the monkey appeared to be symmetrical in the static state and slightly asymmetrical during facial movement,and that they could actively close their eyelids completely.The degree of recovery from facial paralysis reached House-Brackmann grade II in both groups.Compound muscle action potentials were recorded and orbicularis oris muscles responded to electro-stimuli on the surgical side in each monkey.Fluoro Gold-labeled neurons could be detected in the facial nuclei on the injured side.Immunohistochemical staining showed abundant neurofilament-200-positive axons and soluble protein-100-positive Schwann cells in the regenerated nerves.A large number of mid-graft myelinated axons were observed via methylene blue staining and a transmission electron microscope.Taken together,our data indicate that xenogeneic acellular nerve grafts from minipigs are safe and effective for repairing whole facial nerve defects in rhesus monkeys,with an effect similar to that of autologous nerve transplantation.Thus,a xenogeneic acellular nerve graft may be a suitable choice for bridging a whole facial nerve defect if no other method is available.The study was approved by the Laboratory Animal Management Committee and the Ethics Review Committee of the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University,China(approval No.2018-D-1)on March 15,2018.展开更多
Rhesus monkey can not achieve natural delivery due to various reasons,and cesarean section becomes an important midwifery to get infant monkeys. After caesarean section,the pregnant monkey is weak and postoperative wo...Rhesus monkey can not achieve natural delivery due to various reasons,and cesarean section becomes an important midwifery to get infant monkeys. After caesarean section,the pregnant monkey is weak and postoperative wound pain,so it can not personally feed infant monkeys which must be artificially fed. Thus,establishing suitable feeding management program is very important for improving survival rate of infant rhesus monkey and maintaining good health. We summarized food preparation method for infant rhesus monkeys as well as temperature setting and light control,and established the nursing program for newborn infant monkey and daily management process for infant monkeys.展开更多
AIM: To determine the progression of parameters from optical coherence tomography(OCT) in chronic elevated intraocular pressure(IOP) monkeys.METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser...AIM: To determine the progression of parameters from optical coherence tomography(OCT) in chronic elevated intraocular pressure(IOP) monkeys.METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser photocoagulation. Representative OCT parameters, including the average and four-quadrant retinal nerve fiber layer(RNFL) thickness, and parameters from optic nerve head(ONH) analysis were collected before and after laser treatments biweekly for up to 28 wk. The performance of each parameter for early progression detection was analyzed. The progressive trends toward elevated IOP were analyzed using a linear mixed-effects model.RESULTS: There were 10 successfully maintained high IOP eyes in 7 monkeys. The follow-up time was 24±5.37 wk. With cumulative IOP elevation, the cup area, rim area and C/D area ratio were statistically significantly changed as early as 2 wk after elevated IOP induction(P<0.05). The quadrant RNFL thickness changed at 6wk after high IOP induction, and the superior and inferior RNFL thicknesses exhibited more obvious reductions than other quadrants. The average RNFL thickness was the last one to show a significant decrease at 8wk.CONCLUSION: The parameters of ONH are most sensitive to elevated IOP in a primate glaucomatous model. These findings suggest that we should focus on those parameters instead of RNFL thickness in patients with elevated IOP, as they might present with earlier glaucomatous changes.展开更多
Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-...Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. We aim to explore the effects of peroxisome proliferator-activated receptor δ (PPARδ) subtypes on serum lipid profiles in obese rhesus monkey, especially evaluate the efficacy of investigational new drug (HS00098). Methods: First, a prototype of obese rhesus monkey was established by continuously feeding test animals a high fat diet for 2 months. Fifteen obese rhesus monkeys were randomly divided into 3 groups, and the 2 test groups were treated with GW 501516 and HS00098. The test groups were administered doses of 0.3 mg/kg for 1 month, then with 1 mg/kg for 1 month, and finally with 3 mg/kg for 1 month. The control group received placebo treatment. In each experiment, the body weight of each animal was measured and recorded initially and prior to changing the dose of the drug each month. The total cholesterol, blood glucose, triglyceride, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum Apo-A1, Apo-B100 and insulin were tested. Results: The average body weight gain of the GW501516 and HS00098 groups was significantly lower than that of the control group. The group receiving the HS00098 treatment had a higher signifycant increase in high density lipoprotein and apo-A1 (P < 0.05) than the control monkeys, while the total cholesterol, triglycerides, low density lipoproteins, apo-B100, and insulin (P < 0.05 or P < 0.01) were significantly decreased. Compared with GW50-1516, the effects of HS00098 on serum lipid profiles in diet-induced obese rhesus monkeys are more obvious. Conclusion: These results suggested that the investigational drug (HS00098) can effectively reduce body weight, blood lipid and blood sugar levels of diet-induced obese rhesus monkeys.展开更多
Nonhuman primates are closest to humans in terms of lineage,and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans.Therefore,nonhuman primates coul...Nonhuman primates are closest to humans in terms of lineage,and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans.Therefore,nonhuman primates could be utilized to simulate the process of ischemic stroke in the human.Few studies,however,have reported the use of endovascular technology to establish a rhesus monkey stroke model.In the present study,seven adult,male,rhesus monkeys were selected and,following anesthesia,a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow,thereby resulting in middle cerebral artery occlusion.After 2 hours,the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion.Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery.Magnetic resonance imaging revealed the existence of ischemic brain lesions,and neurological examination showed sustained functional deficits following surgery.The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non-craniotomy invasion and reproducibility.The scope and degree of ischemic damage using this model was controllable.Therefore,this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.展开更多
基金supported by the Max Planck Society to C.W.T.and National Institutes of Health USDHHS(R01-HD065826to M.G.,OD011107 to Harris Lewin)。
文摘Fluoxetine(Prozac^(TM))is the only antidepressant approved by the US Food and Drug Administration(FDA)for the treatment of major depressive disorder(MDD)in children.Despite its considerable efficacy as a selective serotonin reuptake inhibitor,the possible long-term effects of fluoxetine on brain development in children are poorly understood.In the current study,we aimed to delineate molecular mechanisms and protein biomarkers in the brains of juvenile rhesus macaques(Macaca mulatta)one year after the discontinuation of fluoxetine treatment using proteomic and phosphoproteomic profiling.We identified several differences in protein expression and phosphorylation in the dorsolateral prefrontal cortex(DLPFC)and cingulate cortex(CC)that correlated with impulsivity in animals,suggesting that the GABAergic synapse pathway may be affected by fluoxetine treatment.Biomarkers in combination with the identified pathways contribute to a better understanding of the mechanisms underlying the chronic effects of fluoxetine after discontinuation in children.
基金supported by the National Program on Key Basic Research Project(973 Programs 2015CB755605)the National Natural Science Foundation of China(81471312)
文摘Viral vector transfection systems are among the simplest of biological agents with the ability to transfer genes into the central nervous system.In brain research,a series of powerful and novel gene editing technologies are based on these systems.Although many viral vectors are used in rodents,their full application has been limited in non-human primates.To identify viral vectors that can stably and effectively express exogenous genes within nonhuman primates,eleven commonly used recombinant adeno-associated viral and lentiviral vectors,each carrying a gene to express green or red fluorescence,were injected into the parietal cortex of four rhesus monkeys.The expression of fluorescent cells was used to quantify transfection efficiency.Histological results revealed that recombinant adeno-associated viral vectors,especially the serotype 2/9 coupled with the cytomegalovirus,human synapsin I,or Ca2+/calmodulin-dependentproteinkinaseII promoters,and lentiviral vector coupled with the human ubiquitin C promoter,induced higher expression of fluorescent cells,representing high transfection efficiency.This is the first comparison of transfection efficiencies of different viral vectors carrying different promoters and serotypes in non-human primates(NHPs).These results can be used as an aid to select optimal vectors to transfer exogenous genes into the central nervous system of non-human primates.
基金supported by the National Natural Science Foundation of China,No.31571109,81460261the Chinese-Finnish Joint Project Fund,No.813111172+2 种基金a grant from the Yunnan Key Program of Science and Technology of China,No.2014FC005the Key Science and Technology Research Project Fund of Hainan Province of China,No.ZDYF2016156the National Clinical Key Subject Construction Project Fund of China
文摘Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells.Therefore,neural stem cell transplantation can be used to promote functional recovery of the nervous system.Rhesus monkey neural stem cells(1×105 cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions.Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well.Transplanted cells were detected at the lesion site,but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum.Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall,and integrated into the recipient brain.Behavioral tests revealed that spatial learning and memory ability improved,indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.
基金the Natural Science Foundation of Shandong Province, No. Y2004C04
文摘BACKGROUND: Insulin-like growth factor-I(IGF-1), as one of the important members of growth factor family, participants in the regulation of many physiological functions and behaviors, having very strong neuroprotective effect. However, the expression of IGF-1 following cerebral ischemia/reperfusion is still disputed. OBJECTIVE: To observe the expression of IGF-1 and protein of corpora striata in ischemic side at the early stage of middle cerebral artery ischemia/reperfusion in rhesus monkey. DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University. MATERIALS: ① Totally 17 rhesus monkeys , of either gender, aged 4 to 5 years, were enrolled . Seven rhesus monkeys observed with gene chip were randomly divided into 2 groups: sham operation group (n=3) and ischemia/reperfusion group (n=4). Ten rhesus monkeys observed with in situ hybridization and immunohistochemistry method were randomly divided into 2 groups: sham operation group (n=3)and ischemia/reperfusion group (n=7). Rhesus monkeys observed under microscope were divided into 2 groups: sham operation group (n=6) and ischamia/reperfusion group (n=11). ② Materials used in the experiment: cresyl violet (Sigma Company, America); immunohistochemical reagent kit ( Huamei Bio-engineering Company); In situ hybridization reagent kit (Boshide Bio-engineering Co.Ltd, Wuhan); 12 800 dots chip (Boxing Company, Shanghai). METHODS: This experiment was carried out at the Institute of Cerebrovascular Disease, Affiliated Hospital of Medical College of Qingdao University from January 2001 to December 2003. ① The onset area of middle cerebral artery was blocked for 2 hours, middle cerebral artery ischemia/reperfusion models were created. ② After ischemia/reperfusion for 24 hours, cerebral tissue sections of rhesus monkeys were prepared and stained with cresyl violet. Image analysis was performed with 500IW image analysis software. Morphological change of corpora striata of operative side was observed in the rhesus monkeys between two groups. Total RNA was extracted from cerebral tissue. ③ Detection of gene chip: Cy3-duTP and Cy5-duTP were used to respectively perform reverse transcription labeling. The sample was reversely transcribed into cDNA, then hybridized with cDNA of cerebral tissue. Genes with the separate absolute value of cy3 and cy5>800, cy3/cy5 > 2(high expression) or < 0.5 (low expression) were found out. Those were genes with differential expression. ④ The expressions of IGF-1 mRNA and protein level of corpora striata in ischemic side of rhesus monkeys were detected between sham operation group and ischemia/reperfusion group at 9 and 24 hours after ischemia/reperfusion with in situ hybridization method and immunohistochemical method. Brown granules were IGF-1 protein positive cells. ⑤ Analysis of variance was used in the difference comparison of measurement data among groups. MAIN OUTCOME MEASURES: ① Change of morphological structure of corpora striata at ischemic side in rhesus monkeys. ② Change of cerebral gene expression profiles at ischemia/reperfusion in rhesus monkeys between two groups. ③ Expression of IGF-1 mRNA and protein level of corpora striata at ischemia/reperfusion in rhesus monkeys between two groups. RESULTS: ① Pathological change : Obvious pathological change of cerebral infarction appeared in the ischemia and reperfusion group, while there was no such pathological change in the sham operation group. ② Change of gene expression profile : There were 4480 genes with difference expression in the ischemia/reperfusion group and sham-operation group, in which, 260 genes had high expression and their absolute value was over 800, and 63 genes had low expression. cy3/cy5 of IGF-1 was 0.379, being relative low expression. ③ IGF-1 mRNA and protein positive cell counts in corpora striata at cerebral ischemic side[IGF-1 mRNA:(9.72±1.18),(9.11±0.76),(14.77±0.60) counts/field;IGF-1 protein:(15.11±1.83),(15.39±0.78),(34.62±0.97)counts/field,P < 0.05-0.01]. CONCLUSION: IGF-1 mRNA and protein are lowly expressed in middle cerebral artery of rhesus monkeys at ischemia/reperfusion.
文摘A recent study by researchers at the Kunming Institute of Zoology (KIZ) of the Chinese Academy of Sciences (CAS) identifies the albinism gene of rhesus monkeys using the method of molecular technology, and suggests the age of the albinism gene in rhesus monkeys should be roughly 800,000 years. The general albinism
基金the CAMS Initiative for Innovative Medicine,No.2016-I2M-1-019National Natural Science Foundation of China,No.31700154+4 种基金Major Science and Technology Special Project of Yunnan Province(Biomedicine),No.2018ZF006Science and Technology Project of Yunnan Province-general program,No.2016FB034Science and Technology Innovation Team Project of Kunming,No.2016-2-R-07674the Project of National Nonprofit Scientific Institutes Basic Scientific Service Fee,No.2016ZX310179-4Science and Technology Project of Yunnan Province,Key New Product Development,No.2014BC008
文摘AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.
文摘AIM:In order to improve the biocompatibility of intraocular lenses(IOL),the polymethylmethacrylate(PMMA)IOL was modified with F-heparin. METHODS:The PMMA IOL was modified with F ions and heparin by the technique of ion beam combined with low temperature and low pressure plasma.The monkeys(20 eyes)with cataract partly were randomly classified into 2 groups and implanted with PMMA IOL and modified IOL respectively for 180 days.All of the eyes were examined by slit-lamp microscope at postoperative 15,30,60,90,180 days.The extracted IOL was analyzed with computer image analysis,light microscope(LM)and scanning electron microscope(SEM)at postoperative 180 days. RESULTS:The early inflammatory reactions postoperatively include anterior chamber exudation and aqueous cell count. The modified IOL group showed less than the non-modified IOL group.The late foreign body cell reaction that adhered to the surface of non-modified IOL was more predominant.The morphologic and pathological changes of posterior capsule opacification(PCO)in monkeys’ eyes included fibrosis-type, pearl-type and soemmerring’s ring.There was a significant difference between the two groups. CONCLUSION:F-heparin modified IOL has good uveal and capsular biocompatibility.
基金supported by the National Natural Science Foundation of China(31700910)Applied Basic Research Programs of Science and Technology Commission Foundation of Yunnan Province(2017FB109)
文摘DEAR EDITOR,Major depressive disorder (MDD), commonly known as depression, is a mental disease characterized by a core symptom of low mood. It lasts at least two weeks (Badamasi et al., 2019;Wang et al., 2019) and is frequently accompanied by low self-esteem, loss of interest in routinely enjoyable activities, low energy, and unexplained pain (Huey et al., 2018;Park et al., 2012;Post & Warden, 2018;Rice et al., 2019;Xiao et al., 2018). Approximately 2%–8% of adults with MDD commit suicide (Richards & O'Hara, 2014;Strakowski & Nelson, 2015), and around half of suicidal individuals suffer depression or other mood disorders (Bachmann, 2018).
基金Acknowledgment This study was supported by the National Natural Science Foundation of China （30230190）, the National Basic Science Research and Development Project （973） （G1999055901） and the Chinese Academy of Sciences （CAS） Knowledge Innovation Program （KSCX-2-SW-201）.
文摘Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).
文摘Taihang Mountain area, a high Incidence area of human esophageal cancer in Northern China. 124 Rhesus monkeys (Macacs Mulatta) were caught in the area in January 1989. Among them, two monkeys died of esophageal carcinoma in 1990. Case 1, a male monkey about 6. 5 yean old and weighing 14. 5 kg, had symptoms of salivation, vomiting and dysphagia in Fabruary 1990. The symptoms became gradually more serious and died in march 1990. Postmortem examination revealed a huge tumor in the distal segment of esophagus, causing severe structure of the organ. The tumor was classified as medullary type and histopathologically diagnosed as a well differentiated squamous cell carcinoma, with metastases to mediastinum and lymph nodes of right gastric group. Case 2, a female monkey ablut 11-year-old and weighing 10. 0 kg, showed loss of appetite, tiredness, somnolence, caughing and vomiting in September and died in December 1990. Autopsy revealed an annular tumor involving the whole clcumference of lower portion of the
基金supported by grants from the Natural Science Foundation of Hunan Province(11JJ4078)the National Natural Science Foundation of China(30900359 and 30900377)
文摘BACKGROUND:Pig islet xenotransplantation has the potential to overcome the shortage of donated human islets for islet cell transplantation in type 1 diabetes.Testing in nonhuman primate models is necessary before clinical application in humans.Intraportal islet transplantation in monkeys is usually performed by surgical infusion during laparotomy or laparoscopy.In this paper,we describe a new method of percutaneous transhepatic portal catheterization(PTPC) as an alternative to current methods of islet transplantation in rhesus monkeys.METHODS:We performed ultrasound-guided PTPC in five adult rhesus monkeys weighing 7-8 kg,with portal vein catheterization confirmed by digital subtraction angiography.We monitored for complications in the thoracic and abdominal cavity.To evaluate the safety of ultrasound-guided PTPC,we recorded the changes in portal pressure throughout the microbead transplantation procedure.RESULTS:Ultrasound-guided PTPC and infusion of 16 000 microbeads/kg body weight into the portal vein was successful in all five monkeys.Differences in the hepatobiliary anatomy of rhesus monkeys compared to humans led to a higher initial complication rate.The first monkey died of abdominal hemorrhage 10 hours post-transplantation.The second suffered from a mild pneumothorax but recovered fully after taking only conservative measures.After gaining experience with the first two monkeys,we decreased both the hepatic puncture time and the number of puncture attempts required,with the remaining three monkeys experiencing no complications.Portal pressures initially increased proportional to the number of transplanted microbeads but returned to preinfusion levels at 30 minutes post-transplantation.The changes in portal pressures occurring during the procedure were not significantly different.CONCLUSIONS:Ultrasound-guided PTPC is an effective,convenient,and minimally invasive method suitable for use in non-human primate models of islet cell transplantation provided that care is taken with hepatic puncture.Its advantages must be weighed against the risks of procedure-related complications.
基金Key Scientific and Technological projects of China (2004BA719A14) and Yunnan province (2004NG12, 2006PT08)National 973 project of China (2006CB504200, 2006CB504300)+3 种基金The Natural Science Foundation of China (30471605 30671960)The Knowledge Innovation Program (KSCX1-YW-R-15)"Western Light" Projects of Chinese Academy of Sciences.
文摘In the present research,two Chinese rhesus monkeys were inoculated intravenously with 5000 TCID50 of SIVmac239. The changes in the numbers of CD4+ T lymphocyte in peripheral blood,plasma viral loads,proviral DNA and humoral antibodies against virus were periodically monitored during 121 days. At the early stage of infection,proviral DNA had been detected in PBMCs,and infectious SIVmac239 virus had been isolated from PBMCs. At the same period,the numbers of CD4+ T lymphocytes were significantly decreased,and maintained at low level during the 121-day period of infection. Plasma viral loads reached the peak at week 2 post-inoculation and kept at a steady state subsequently. Moreover,antibodies against viral proteins were detected from plasma. All the results showed that the two Chinese rhesus monkeys had been infected with SIVmac239 successfully. This animal model can be applied for further AIDS researches.
基金financially supported by the National Natural Science Foundation of China,No.81770990(to GCZ)Jiangsu Provincial Key Research and Development Program of China,No.BE2018628(to GCZ)+2 种基金Six Talent Peaks Project in Jiangsu Province of China,No.2019-WSW-141(to GCZ)Major Medicine Projects of Wuxi Health Commission of Jiangsu,China,No.Z201802(to DJX)Precision Medicine Projects of Wuxi Health Commission of Jiangsu,China,No.J202002(to GCZ)。
文摘Acellular nerve allografts conducted via chemical extraction have achieved satisfactory results in bridging whole facial nerve defects clinically,both in terms of branching a single trunk and in connecting multiple branches of an extratemporal segment.However,in the clinical treatment of facial nerve defects,allogeneic donors are limited.In this experiment,we exposed the left trunk and multiple branches of the extratemporal segment in six rhesus monkeys and dissected a gap of 25 mm to construct a monkey model of a whole left nerve defect.Six monkeys were randomly assigned to an autograft group or a xenogeneic acellular nerve graft group.In the autograft group,the 25-mm whole facial nerve defect was immediately bridged using an autogenous ipsilateral great auricular nerve,and in the xenogeneic acellular nerve graft group,this was done using a xenogeneic acellular nerve graft with trunk-branches.Examinations of facial symmetry,nerve-muscle electrophysiology,retrograde transport of labeled neuronal tracers,and morphology of the regenerated nerve and target muscle at 8 months postoperatively showed that the faces of the monkey appeared to be symmetrical in the static state and slightly asymmetrical during facial movement,and that they could actively close their eyelids completely.The degree of recovery from facial paralysis reached House-Brackmann grade II in both groups.Compound muscle action potentials were recorded and orbicularis oris muscles responded to electro-stimuli on the surgical side in each monkey.Fluoro Gold-labeled neurons could be detected in the facial nuclei on the injured side.Immunohistochemical staining showed abundant neurofilament-200-positive axons and soluble protein-100-positive Schwann cells in the regenerated nerves.A large number of mid-graft myelinated axons were observed via methylene blue staining and a transmission electron microscope.Taken together,our data indicate that xenogeneic acellular nerve grafts from minipigs are safe and effective for repairing whole facial nerve defects in rhesus monkeys,with an effect similar to that of autologous nerve transplantation.Thus,a xenogeneic acellular nerve graft may be a suitable choice for bridging a whole facial nerve defect if no other method is available.The study was approved by the Laboratory Animal Management Committee and the Ethics Review Committee of the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University,China(approval No.2018-D-1)on March 15,2018.
基金Supported by Yunnan Technology Innovation Talent Project(2014HB090)Kunming Science and Technology Planning Project(2014-04-A-S-02-3074)
文摘Rhesus monkey can not achieve natural delivery due to various reasons,and cesarean section becomes an important midwifery to get infant monkeys. After caesarean section,the pregnant monkey is weak and postoperative wound pain,so it can not personally feed infant monkeys which must be artificially fed. Thus,establishing suitable feeding management program is very important for improving survival rate of infant rhesus monkey and maintaining good health. We summarized food preparation method for infant rhesus monkeys as well as temperature setting and light control,and established the nursing program for newborn infant monkey and daily management process for infant monkeys.
基金Supported by National Natural Science Foundation of China(No.81470627 No.81600726)+2 种基金Shandong Province Natural Science Foundation(No.ZR2016HB53)Natural Science Foundation of Guangdong Province(No.2018A030310185)the Research Funding of Guangzhou Medical University(No.2016C21)
文摘AIM: To determine the progression of parameters from optical coherence tomography(OCT) in chronic elevated intraocular pressure(IOP) monkeys.METHODS: A chronic elevated IOP model of rhesus monkeys was induced by laser photocoagulation. Representative OCT parameters, including the average and four-quadrant retinal nerve fiber layer(RNFL) thickness, and parameters from optic nerve head(ONH) analysis were collected before and after laser treatments biweekly for up to 28 wk. The performance of each parameter for early progression detection was analyzed. The progressive trends toward elevated IOP were analyzed using a linear mixed-effects model.RESULTS: There were 10 successfully maintained high IOP eyes in 7 monkeys. The follow-up time was 24±5.37 wk. With cumulative IOP elevation, the cup area, rim area and C/D area ratio were statistically significantly changed as early as 2 wk after elevated IOP induction(P<0.05). The quadrant RNFL thickness changed at 6wk after high IOP induction, and the superior and inferior RNFL thicknesses exhibited more obvious reductions than other quadrants. The average RNFL thickness was the last one to show a significant decrease at 8wk.CONCLUSION: The parameters of ONH are most sensitive to elevated IOP in a primate glaucomatous model. These findings suggest that we should focus on those parameters instead of RNFL thickness in patients with elevated IOP, as they might present with earlier glaucomatous changes.
文摘Aim Activation of peroxisome proliferator-activated receptor δ (PPARδ) subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. We aim to explore the effects of peroxisome proliferator-activated receptor δ (PPARδ) subtypes on serum lipid profiles in obese rhesus monkey, especially evaluate the efficacy of investigational new drug (HS00098). Methods: First, a prototype of obese rhesus monkey was established by continuously feeding test animals a high fat diet for 2 months. Fifteen obese rhesus monkeys were randomly divided into 3 groups, and the 2 test groups were treated with GW 501516 and HS00098. The test groups were administered doses of 0.3 mg/kg for 1 month, then with 1 mg/kg for 1 month, and finally with 3 mg/kg for 1 month. The control group received placebo treatment. In each experiment, the body weight of each animal was measured and recorded initially and prior to changing the dose of the drug each month. The total cholesterol, blood glucose, triglyceride, high density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum Apo-A1, Apo-B100 and insulin were tested. Results: The average body weight gain of the GW501516 and HS00098 groups was significantly lower than that of the control group. The group receiving the HS00098 treatment had a higher signifycant increase in high density lipoprotein and apo-A1 (P < 0.05) than the control monkeys, while the total cholesterol, triglycerides, low density lipoproteins, apo-B100, and insulin (P < 0.05 or P < 0.01) were significantly decreased. Compared with GW50-1516, the effects of HS00098 on serum lipid profiles in diet-induced obese rhesus monkeys are more obvious. Conclusion: These results suggested that the investigational drug (HS00098) can effectively reduce body weight, blood lipid and blood sugar levels of diet-induced obese rhesus monkeys.
基金the National High Technology Program of China,No.2006AA02A117
文摘Nonhuman primates are closest to humans in terms of lineage,and middle cerebral artery ischemia/reperfusion responses of nonhuman primates are most similar to ischemic stroke in humans.Therefore,nonhuman primates could be utilized to simulate the process of ischemic stroke in the human.Few studies,however,have reported the use of endovascular technology to establish a rhesus monkey stroke model.In the present study,seven adult,male,rhesus monkeys were selected and,following anesthesia,a microcatheter was inserted into one side of the middle cerebral artery via the femoral artery to block blood flow,thereby resulting in middle cerebral artery occlusion.After 2 hours,the microcatheter was withdrawn to restore the middle cerebral artery blood flow and to establish ischemia/reperfusion.Results from angiography and magnetic resonance angiography confirmed occlusion and reopening of the middle cerebral artery.Magnetic resonance imaging revealed the existence of ischemic brain lesions,and neurological examination showed sustained functional deficits following surgery.The rhesus monkey middle cerebral artery ischemia/reperfusion models established by microcatheter embolization had the advantage of non-craniotomy invasion and reproducibility.The scope and degree of ischemic damage using this model was controllable.Therefore,this nonhuman primate model is an ideal model for cerebral ischemia and reperfusion.
