Changman ZhouBeijing Medical University
Changman Zhou
MD. Ph.D
About
80
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Publications
Publications (80)
Background:
Decreased estrogen levels can cause abnormal thermosensitivity of the preoptic area (POA) in the hypothalamus during menopause, which may cause hot flashes. Thermosensitive transient receptors (ThermoTRPs) affect the thermosensitivity of neurons. It is worth exploring whether ThermoTRPs change under low estrogen state and participate i...
Background
Menopausal symptoms can affect the physical and mental health of females and are often related to abnormal function of the hypothalamus. In this study, we evaluated changes in the hypothalamus transcriptome in ovariectomized mice to identify key mRNAs, and systematically elucidated the possible molecular mechanisms underlying the menopau...
Background
Hot flashes (HF) caused by low estrogen in menopause result from changes in thermoregulatory processes in the hypothalamic preoptic area (POA). In the POA, transient receptor potential vanilloid 1 (TRPV1) participates in heat dissipation processes. Studies suggest that TRPV1 expression may be regulated by norepinephrine (NE)-activated α2...
Ischemic stroke is a leading cause of death and disability worldwide. Advances in early recognition of stroke symptoms and the transport of patients to specialized stroke centers has been a major step in improvement of mortality and morbidity. Speed is essential since current intravenous thrombolytic treatments can only be delivered in a very narro...
Early brain injury (EBI) refers to the direct injury to the brain during the first 72 h after subarachnoid hemorrhage (SAH), which is one of the major causes for the poor clinical outcome after SAH. In this study, we investigated the effect and the related mechanism of Salvinorin A (SA), a selective kappa opioid receptor agonist, on EBI after SAH....
Objectives
In this study, the effects of team-based learning (TBL) method on the anatomy course for students in People’s Republic of China were assessed.
Methods
The students were randomly divided into the traditional lecture-based teaching group (traditional learning [TL] group, 99 students) and TBL teaching group (98 students). The TBL method re...
Objectives:
This study aimed to demonstrate the potential of Salvinorin A (SA) for cerebral vasospasm after subarachnoid hemorrhage (SAH) and investigate mechanisms of therapeutic effect using rat SAH model.
Methods:
SA was injected intraperitoneally and the neurobehavioral changes were observed at 24h, 48h and 72h after SAH. Basilar artery was...
Oxymatrine, a quinolizidine natural drug extracted from Sophora japonica, has been reported to have neuroprotective effect and cardioprotective effect. However, the protective effect of oxymatrine on arsenic trioxide (As2O3)-induced liver injury has not been reported. In the present study, we investigated the protective effects of oxymatrine on As2...
Loss of von Hippel-Lindau tumor suppressor protein (VHL) or hypoxia results in nuclear relocalization of PDCD5 and subsequent mouse double minute 2 homolog (Mdm2) degradation. Thus, VHL may involved in the PDCD5 mediated apoptosis and autophagy after MCAO. In the present study, using PDCD5 knockout (PDCD5-/-) mice, we aimed to demonstrate that knoc...
Unlabelled:
Ganglioside GM1, which is particularly abundant in the central nervous system (CNS), is closely associated with the protection against several CNS disorders. However, controversial findings have been reported on the role of GM1 following ischemic stroke. In the present study, using a rat middle cerebral artery occlusion (MCAO) model, w...
The ARRIVE Guidelines Checklist.
Animal Research: Reporting In Vivo Experiments.
(PDF)
Background and purpose
Methylene blue (MB) USP, which has energy‐enhancing and antioxidant properties, is currently used to treat methemoglobinemia and cyanide poisoning in humans. We recently showed that MB administration reduces infarct volume and behavioral deficits in rat models of ischemic stroke and traumatic brain injury. This study reportst...
Granulocyte-colony stimulating factor (G-CSF), a growth factor, has known neuroprotective effects in a variety of experimental brain injury models. Herein we show that G-CSF administration attenuates neuronal apoptosis after neonatal hypoxia-ischemia (HI) via glycogen synthase kinase-3 beta (GSK-3 beta) inhibition. Ten day old Sprague-Dawley rat pu...
Previous reports have indicated that exogenous bone morphogenetic protein-7 (BMP-7) has a neuroprotective effect after cerebral ischemia injury and promotes motor function recovery, but the appropriate BMP-7 concentration and time course are unclear. Here, we assessed endogenous BMP-7 expression in hypoxia and ischemia-damaged brain tissues and inv...
The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early period following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48hours after SAH injury in rats. Specifically evaluating whether mitop...
The term mitophagy is coined to describe the selective removal of mitochondria by autophagy but the process itself is still contentious, especially in the early brain injury following subarachnoid hemorrhage (SAH). In the present study, we investigated the role of mitophagy following 48hours after SAH injury in rats. Specifically evaluating whether...
Oxygen inhalation has been shown to increase oxygen supply to tissues after cerebral ischemia/ reperfusion injury, protecting injured neural cells. However, hyperbaric oxygen may aggravate oxidative stress. By contrast, normobaric oxygen has the rapid and non-invasive characteristics and may have therapeutic effects on ischemic/hypoxic disease. Rat...
Amyotrophic lateral sclerosis (ALS) is a fatal disease that involves the degeneration of cortical and spinal motor neurons. Mutant SOD1 (G93A) rats constitute a good animal model for this pathological condition. We have previously demonstrated that transplantation of neonatal olfactory ensheathing cells (OECs) into the dorsal funiculus of the spina...
Aim
We found for the first time that Programmed Cell Death 5 (PDCD5) plays an essential role in brain ischemic injury in a rat focal cerebral ischemia model. We hypothesized that down‐regulating PDCD5 can protect the brain from ischemic damage by inhibiting PDCD5 induced apoptotic pathway.
Methods
105 Sprague‐Dawley male rats weighing 280 to 300 g...
Plasma thrombin concentration is increased after subarachnoid hemorrhage (SAH). However, the role of thrombin receptor (protease-activated receptor-1 [PAR-1]) in endothelial barrier disruption has not been studied. The aims of this study were to investigate the role of PAR-1 in orchestrating vascular permeability and to assess the potential therape...
This study aimed to study whether the problem-based learning (PBL) as an educational strategy can be of great help in improving the quality of gross anatomy and the attitude of students towards the learning method in China. It was performed in Basic Science of Peking University Health Science Center. The study sample included 200 students and they...
Objective
To investigate the effect of pretreatment of inhalation of normobaric oxygen(NBO) on the injury induced by focal cerebral ischemia via HIF‐notch pathway.
Methods
Male SD rats were randomly divided into four groups: Control (sham surgery), Middle Cerebral Artery Occlusion and Reperfusion(MCAO), MCAO pretreated with Normobaric Oxygen (NBO)...
mTOR pathway promotes cell proliferation under environmental stress. In the present study, we investigated the role of mTOR pathway in subarachnoid hemorrhage brain injury. Thirty dogs were randomly divided into 5 groups: sham, SAH, SAH+DMSO, SAH + Rapamycin and SAH+AZD8055. An established canine double‐hemorrhage model of SAH was used by injecting...
Transmembrane protein 166 (TMEM166) is a lysosomal/endoplasmic reticulum-associated protein found in various species where it acts as a regulator of programmed cell death, mediating both autophagy and apoptosis. In the present study, we investigated the role of TMEM166 following MCAO injury in rats to determine whether the structural damages follow...
Mammalian target of rapamycin (mTOR) pathway is a serine/threonine protein kinase that plays a vital role in regulating growth, proliferation, survival, and protein synthesis among cells. In the present study, we investigated the role of the mTOR pathway following subarachnoid hemorrhage brain injury--specifically investigating its ability to media...
Black cohosh (Cimicifuga racemosa) is widely used in menopause symptoms strategy.
The aim of this study was to examine the effect of isopropanolic black cohosh extract (iCR) on the central body temperature (CBT) of ovariectomized rats (OVX) and elaborate its possible effects in alleviating menopause related hot flushes.
64 female Sprague-Dawley rat...
The blood-brain barrier (BBB) plays a vital role as both a physiologic and physical barrier in regulating the movement of water from the vasculature to the brain. During a subarachnoid hemorrhage (SAH), the BBB is disrupted by a variety of mediators, one of which can result in endothelial cell death. As a result, in the present study, we investigat...
Because the potential neuroprotective effect of isoflurane is controversial, we attempted to study whether isoflurane after treatment provides neuroprotection in a rat model of hyperglycemia-induced ischemic hemorrhagic transformation.
Rats received an injection of 50% dextrose (6 mL/kg intraperitoneally) and had a middle cerebral artery occlusion...
Amyotrophic lateral sclerosis (ALS) is a progressively fatal, incurable, neurodegenerative disorder. In this study, we investigated whether olfactory ensheathing cells (OEC) transplantation could provide protection to motor neurons and enable remyelination in mutant SOD1(G93A) transgenic rats with ALS. Seventy-two rats were divided into four groups...
The initial mechanical tissue disruption of spinal cord injury (SCI) is followed by a period of secondary injury that increases the size of the lesion. Secondary injuries are associated with edema, inflammation, excessive cytokine release, excitotoxicity and cell apoptosis. 3,4-dihydroxyphenyl lactic acid (DLA) is one of the major water-soluble com...
Various studies on focal cerebral ischemic models have implicated the direct activation and expression of matrix metalloproteinases (MMPs), especially MMP-9, as a key orchestrator of blood-brain barrier (BBB) disruption. Moreover, studies have shown that MMP-9 siRNA can protect the BBB from ischemia/reperfusion injury. In the present study, we inve...
We evaluated a role of hypoxia-inducible factor-1alpha (HIF-1alpha) and its downstream genes in acute hyperglycemia-induced hemorrhagic transformation in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats weighing 280-300 g (n = 105) were divided into sham, 90 min middle cerebral artery occlusion (MCAO), MCAO plus HIF-1alpha inhibitor...
The multidrug resistance protein P-glycoprotein (P-gp) is physiologically expressed at the bile canalicular membrane of the liver, where it participates in the biliary excretion of various lipophilic drugs. Chronic exposure to carbon tetrachloride (CCI(4)) is known to induce hepatic fibrosis resulting in hepatotoxicity. This study focuses on the ef...
Problem-based learning (PBL) has been introduced to medical schools around the world and has increasingly become a popular pedagogical technique in Asian countries since 1990. Gross anatomy is a fundamental basic science course in virtually all medical training programs, and the methods used to teach it are under frequent scrutiny and revision. Stu...
Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease. SOD1G93A rat(n=20), medium+SOD1G93A rat(n=20), OECs+SOD1G93A rat(n=20), and another 20 wild type rats as control. 5μL(1×105) OECs was injected into the dorsal funiculus of the thoracic spinal cord (T7) through a glass micropipette at depths of 0.7 mm and 0.4 mm (0...
Trials of neuroprotection in ischemic stroke mainly concern gray matter protection, with little information on white matter damage. Olfactory ensheathing cells (OECs) are capable of providing continuous neurotrophic factor and of promoting growth and remyelination of damaged axons. We evaluated OECs for the repair of white matter after transplantat...
Clinical studies have expanded the therapeutic olfactory ensheathing cells (OECs) transplantation to different human Central Nervous System (CNS) diseases. In fact, the OEC transplantation in clinic is a mixture of olfactory bulb cells; they even have not demonstrated that they have such a subpopulation yet. However, as a source of OECs transplanta...
Triple florescence labeling of human fetal olfactory ensheathing cells in culture under confocal microscopy. Red: p75, Green: GFAP, Blue: hoechest. In this issue, by Liu et al., on page 359.
Successful repair of damage in cerebral palsy (CP) needs effective clinical interventions other than simply symptomatic treatments. To elucidate the feasibility of using olfactory ensheathing cells (OECs) to treat CP in children and adolescents, we conducted a randomized controlled clinical trial (RCT) on 33 patients. The patients were randomly ass...
Notch signaling plays an important role in the arteriogenesis. We hypothesized that the Notch inhibitor--gamma-secretase inhibitor (GSI1) exerted its effects on the vasospasm via regulation of NF-kappaB and MMP-9. In this study, 160 male Sprague-Dawley (SD) rats were randomly assigned into four groups: Sham, subarachnoid hemorrhage (SAH), SAH treat...
Hypoxia-inducible factor-1 (HIF-1) plays an essential role in cerebral ischemia as a proapoptotic factor. We hypothesized that HIF-1alpha siRNA can protect the brain from ischemic damage by inhibiting HIF-1alpha induced apoptotic pathway at the RNA level in a rat focal ischemic model. Results showed that treatment with HIF-1alpha siRNA reduced the...
RNA interference appears to have a great potential not only as an in vitro target validation, but also as a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. We hypothesize that MMP-9 siRNA can be effective as an MMP-9 protein inhibitor in a rat focal ischemia model. Male Sprague-Dawley rats (156) wer...
Our previous study demonstrated that p53 plays an orchestrating role in the vasospasm and apoptotic cell death after subarachnoid hemorrhage (SAH). We now hypothesize that p53 also plays an important role in brain edema by up-regulating the expression of MMP-9 via the NF-kappaB molecular signaling pathway. Adult male rats (300-350 g) were divided i...
BackgroundRecent studies have demonstrated that apoptosis in cerebral arteries could play an essential role in cerebral vasospasm after
subarachnoid hemorrhage (SAH) and that SP600125, an inhibitor of c-Jun N-terminal kinase (JNK) could suppress apoptosis. The
present study examined whether SP600125 could reduce cerebral vasospasm through the suppr...
Recent studies have demonstrated that apoptosis in cerebral arteries could play an essential role in cerebral vasospasm after subarachnoid hemorrhage (SAH) and that SP600125, an inhibitor of c-Jun N-terminal kinase (JNK) could suppress apoptosis. The present study examined whether SP600125 could reduce cerebral vasospasm through the suppression of...
Despite 2-methoxyestradiol (2ME2) and tricyclodecan-9-yl-xanthogenate (D609) having multiple effects on cancer cells, mechanistically, both of them down-regulate hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF). We hypothesize HIF-1alpha plays an essential role in cerebral ischemia as a pro-apoptosis regula...
The microanatomy of the superior orbital fissure (SOF) was studied in 96 sides of cadaver specimens. The SOF is a narrow bony cleft that lies at the apex of the orbit between the greater and lesser wings of the sphenoid. Through this fissure, many important structures enter the orbit from the middle cranial fossa including the third, fourth, sixth...
2-Methoxyestradiol (2ME2), a naturally occurring metabolite of estradiol, is known to have antiproliferative, antiangiogenic, and antiproapoptotic activities. Mechanistically, 2ME2 has been shown to downregulate hypoxia-inducible factor 1alpha (HIF-1alpha). We hypothesized that hypoxia in the major cerebral arteries might activate a unique signalin...
The major risk factors for intracerebral hemorrhage (ICH) are hypertension and aging. A fundamental mechanism for hypertension- and aging-induced vascular injury is oxidative stress. We hypothesize that oxidative stress has a crucial role in ICH. To test our hypothesis, we used bacterial collagenase to produce ICH in wild-type C57BL/6 and gp91phox...
Inflammation could play a role in cerebral vasospasm after subarachnoid hemorrhage (SAH). SP600125 a c-Jun N-terminal kinase (JNK) inhibitor reduces inflammation. The present study examined if SP600125 could reduce cerebral vasospasm.
Twenty-seven dogs were assigned to 5 groups: control, SAH, SAH plus dimethyl sulfoxide (DMSO), SAH plus SP600125 (1...
Our previous studies indicate that apoptosis in endothelial cells of major cerebral arteries contributes to cerebral vasospasm after subarachnoid hemorrhage (SAH). This study examined the pathologic roles of tumor suppressor p-53 in cerebral vasospasm using an established dog double-hemorrhage model. Twenty mongrel dogs were divided into four group...
Hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor specifically activated by hypoxia. Activation of proapoptotic caspase-9 and caspase-3 pathways, by binding with tumor suppressor p53, HIF-1alpha could lead to harmful actions such as apoptosis. We examined whether increasing oxygen levels by hyperbaric oxygen (HBO) offers neurop...
We examined the therapeutic effect of human extracellular superoxide dismutase (ECSOD) gene transfer in the prevention of delayed cerebral vasospasm after experimental subarachnoid hemorrhage (SAH) because it was reported ECSOD relieved early-stage vasospasm.
Twenty mongrel dogs were divided randomly into 4 groups to serve as control, SAH, SAH+aden...
Matrix metalloproteinase-9 (MMP-9) participates in the disregulation of blood-brain barrier during hemorrhagic transformation, and exacerbates brain injury after cerebral ischemia. However, the consequences of long-term inhibition or deficiency of MMP-9 activity (which might affect normal collagen or matrix homeostasis) remains to be determined. Th...
Cell death, especially apoptosis, occurred in brain tissues after subarachnoid hemorrhage (SAH). We examined the relationships between apoptosis and the disruption of blood-brain barrier (BBB), brain edema, and mortality in an established endovascular perforation model in male Sprague-Dawley rats.
A pan-caspase inhibitor (z-VAD-FMK) was administere...
We have shown that hyperoxia reduces brain damage in a rat model of hypoxia-ischemia. The purpose of this study was to examine the possibility of hyperoxia in inducing vision-threatening retinopathy. Two different experiments were conducted in this study. PART 1: seven-day-old rat pups were subjected to unilateral carotid artery ligation followed b...
The objective of the present study was to examine the role of the angiotensin II type 1 receptor (AT(1)-R) in the diabetes-aggravated oxidative stress and brain injury observed in a rat model of combined diabetes and focal cerebral ischemia. Diabetes was induced by an injection of streptozotoxin (STZ; 55 mg/kg iv) at 8 wk of age. Two weeks after th...
Mitogen-activated protein kinase (MAPK) has been shown to be involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). In the present study we examined the role of Ras protein, an upstream regulator of MAPK, and the effects of the inhibitors of Ras farnesyltransferase (FTase), FTI-277 and FTase inhibitor I, on angiogra...
Apoptosis in the endothelium of major cerebral arteries may play a role in the initiation and maintenance of cerebral vasospasm after subarachnoid hemorrhage (SAH). We tested the therapeutic effect of caspase inhibitors on endothelial apoptosis and on cerebral vasospasm in an established dog double-hemorrhage model. Thirty-one mongrel dogs were div...
Erythropoietin, a hemotopoietic growth factor, has brain protective actions. This study investigated the mechanisms of Recombinant Human EPO (rhEPO)-induced brain protection in neonates. An established rat hypoxia-ischemia model was used by ligation of the right common carotid artery of 7-day-old pups, followed by 90 minute of hypoxia (8% 02 and 92...
We have previously demonstrated that a transient exposure to hyperbaric oxygen (HBO) attenuated the neuronal injury after neonatal hypoxia-ischemia. This study was undertaken to determine whether HBO offers this neuroprotection by reducing apoptosis in injured brain tissue. Seven-day-old rat pups were subjected to unilateral carotid artery ligation...
Nogo-A, a myelin-associated neurite outgrowth inhibitory protein, binds with the Ng-R receptor to activate RhoA intracellular signals and inhibit the plasticity after CNS injury. We evaluated the effect of hyperbaric oxygen (HBO) on the expression of Nogo-A, Ng-R, and RhoA after transient global ischemia in a rat 2 vessel occlusion global ischemic...
The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h,...
A gene putatively identified as the Archaeoglobus fulgidus inositol-1-phosphate synthase (IPS) gene was overexpressed to high level (about 30-40% of total soluble cellular proteins) in Escherichia coli. The recombinant protein was purified to homogeneity by heat treatment followed by two column chromatographic steps. The native enzyme was a tetrame...
Two phospholipase D (PLD) enzymes with both hydrolase and transferase activities were isolated from Streptomyces chromofuscus. There were substantial differences in the kinetic properties of the two PLD enzymes towards monomeric, micellar, and vesicle substrates. The most striking difference was that the higher molecular weight enzyme (PLD57 approx...
The kinetics of PI-PLCgamma1 toward a water-soluble substrate (inositol 1,2-cyclic phosphate, cIP) and phosphatidylinositol (PI) in detergent mixed micelles were monitored by 31P NMR spectroscopy. That cIP is also a substrate (Km = approximately 15 mM) implies a two-step mechanism (intramolecular phosphotransferase reaction to form cIP followed by...
The techniquein situ hybridization was used to measure the levels of light (NF-L), medium (NF-M) and heavy (NF-H) neurofilament protein subunits
mRNA in L4-6 spinal motoneurons in adult rat during regeneration following a unilateral crush of the sciatic nerve. It was found that
the hybridization signals of each neurofilament subunit rnRNA were dram...
Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis is an allosteric enzyme with both a phospholipid activator site and an active site. The activation of PI-PLC enzyme is optimal with phosphatidylcholine (PC) binding to the activator site and anchoring the enzyme to the interface [Zhou, C., et al. (1997) Biochemistry...
The effect of different phospholipids on the kinetic behavior of phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis toward PI vesicles has been investigated. Cosonicated PC/PI vesicles displayed enhanced hydrolysis of PI when less than 0. 20 mole fraction PC was incorporated into the vesicle; higher mole fractions of...
The solution conformation of chiral diheptanoylphosphatidylinositol (D- and L-inositol isomers) has been characterized by NMR spectroscopy. A positive NOE between the inositol C2 proton and an sn-3 glycerol CH2 proton has been observed in the D- but not in the L-inositol isomer of diheptanoylphosphatidylinositol (PI). Computer modeling using QUANTA...
For many of the enzymes that utilize or produce diacylglycerols, detergent mixed micelles are often used in assay systems to solubilize the lipophilic substrates or products. The assumption is often made that the diacylglycerol (DAG) is solubilized and well mixed throughout the population of micelles during the time course of the assay. In the pres...
Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis exhibits 'interfacial activation' toward the water-soluble substrate myo-inositol 1,2-(cyclic)phosphate [Zhou et al. (1997) Biochemistry 36, 347-355]. The activation of PI-PLC enzyme is optimal with PC or PE interfaces. NMR experiments (TRNOE and 31P line width analy...
Phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillus thuringiensis catalyzes the hydrolysis of phosphatidylinositol (PI) in discrete steps: (i) an intramolecular phosphotransferase reaction to form inositol 1,2-(cyclic)-phosphate (cIP), followed by (ii) a cyclic phosphodiesterase activity that converts cIP to inositol 1-phosphate. W...
Three inositol 1,2-(cyclic)-phosphate analogs, inositol cyclic phosphonates with different stereochemistry at the C-2 position of the inositol ring, have been synthesized as water-soluble inhibitors of phosphatidylinositol-specific phospholipase C (PI-PLC). Their inhibition of both phosphotransferase and cyclic phosphodiesterase activities has been...
PI-specific PLC enzymes are a key component of phosphatidylinositol-mediated signaling pathways since the hydrophobic product, diacylglycerol, activates protein kinase C and the water-soluble product, inositol trisphosphate, is involved in Ca2+ mobilization. Nonspecific, or PC-PLC, enzymes can generate diacylglycerol without Ca2+ mobilization. A se...
A series of symmetric short-chain phosphatidylinositols (PI), including dihexanoyl-PI, diheptanoyl-PI (racemic as well as D and L forms), and 2-methoxy inositol-substituted diheptanoyl-PI, have been synthesized, characterized, and used to investigate key mechanistic questions about phosphatidylinositol-specific phospholipase C (PI-PLC) from Bacillu...