Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries:a meta-analysis

Objective:To judge the efficacies of neural stem cell(NSC)transplantation on functional recovery following contusion spinal cord injuries(SCIs).Data sources:Studies in which NSCs were transplanted into a clinically relevant,standardized rat model of contusion SCI were identified by searching the PubMed,Embase and Cochrane databases,and the extracted data were analyzed by Stata 14.0.Data selection:Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso,Beattie,and Bresnahan lo-comotor rating scale.Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.Outcome measures:The restoration of motor function was assessed by the Basso,Beattie,and Bresnahan locomotor rating scale.Results:We identified 1756 non-duplicated papers by searching the aforementioned electronic databases,and 30 full-text articles met the inclusion criteria.A total of 37 studies reported in the 30 articles were included in the meta-analysis.The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs,to a moderate extent(pooled standardized mean difference(SMD)=0.73;95%confidence interval(CI):0.47–1.00;P<0.001).NSCs obtained from different donor species(rat:SMD=0.74;95%CI:0.36–1.13;human:SMD=0.78;95%CI:0.31–1.25),at different donor ages(fetal:SMD=0.67;95%CI:0.43–0.92;adult:SMD=0.86;95%CI:0.50–1.22)and from different origins(brain-derived:SMD=0.59;95%CI:0.27–0.91;spinal cord-derived:SMD=0.51;95%CI:0.22–0.79)had similar efficacies on improved functional recovery;however,adult induced pluripotent stem cell-derived NSCs showed no significant efficacies.Furthermore,the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery(SMD=0.45;95%CI:0.21–0.70).However,shorter periods between the contusion induction and the NSC transplantation showed slightly higher efficacies(acute:SMD=1.22;95%CI:0.81–1.63;subacute:SMD=0.75;95%CI:0.42–1.09).For chronic injuries,NSC implantation did not significantly improve functional recovery(SMD=0.25;95%CI:–0.16 to 0.65).Conclusion:NSC transplantation alone appears to be a positive yet limited method for the treatment of contusion SCIs.

Behavioral Characteristics of Pharmacologically Selected Lines of Rats: Relevance to Depression

This brief review discusses the behavioral consequences of two pharmacologically selected lines of rats. Flinders Sensitive (FSL) and Flinders Resistant (FRL) Lines of rats were selected on the basis of differential hypothermic and behavioral responses to the anticholinesterase, diisopropylfluorophosphate (DFP). FSL rats are more sensitive to the hypothermic effects of cholinergic, serotonergic, and dopaminergic agonists but less sensitive to the locomotor or stereotypic effects of dopamine agonists. FSL rats exhibit greater immobility in the forced swim test and reduced social interaction compared with FRL rats, but do not differ in saccharin intake, behavior in the elevated plus maze, or responses for rewarding brain self-stimulation. The exaggerated immobility and reduced social interaction are counteracted by chronic treatment with antidepressants. Because FSL rats were more sensitive to 5-HT1A receptor agonists, high (HDS) and low (LDS) 8-OH-DPATsensitive lines were selectively bred for differential hypothermic responses to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT). HDS rats were also more sensitive to the hypothermic effects of oxotremorine, a cholinergic agonist, but selection for this response did not diverge with later selection. HDS rats exhibited greater immobility in the forced swim test than LDS rats and this correlated response could be seen early in selection (generation 3). HDS rats also showed reduced social interaction compared to LDS rats, but did not differ in behavior in the elevated plus maze. These findings confirm that selection for hypothermic responses to pharmacological agents do have behavioral consequences, notably the production of depressive-like phenotypes, which can be counteracted by chronic antidepressant treatment. Because increased 5-HT1A receptor sensitivity was common to both selected lines (FSL and HDS), neurobiological processes dependent on this receptor could contribute to the abnormal behaviors that manifest in these rat lines and thus suggesting a mechanism underlying depressive behaviors in humans. However, available human data are inconsistent with this hypothesis and suggest that other mechanisms underlie these behavioral abnormalities in HDS and FSL rats. These mechanisms as well as additional behavioral testing in these rat lines will be discussed.

Effects of Batroxobin on Spatial Learning and Memory Disorder of Rats with Temporal Ischemia and the Expression of HSP32 and HSP70

The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.

Mechanisms mediating cholinergic antral circular smooth muscle contraction in rats

AIM:To investigate the pathway(s)mediating rat antral circular smooth muscle contractile responses to the cholinomimetic agent,bethanechol and the subtypes of muscarinic receptors mediating the cholinergic contraction. METHODS:Circular smooth muscle strips from the antrum of Sprague-Dawley rats were mounted in muscle baths in Krebs buffer.Isometric tension was recorded.Cumulative concentration-response curves were obtained for(+)-cis- dioxolane(cD),a nonspecific muscarinic agonist,at 10^(-8)- 10^(-4)mol/L,in the presence of tetrodotoxin(TTX,10^(-7)mol/L). Results were normalized to cross sectional area.A repeat concentration-response curve was obtained after incubation of the muscle for 90 min with antagonists for M1(pirenzepine), M2(methoctramine)and M3(darifenadn)muscarinic receptor subtypes.The sensitivity to PTX was tested by the ip injection of 100 mg/kg of PTX 5 d before the experiment.The antral circular smooth muscles were removed from PTX-treated and non-treated rats as strips and dispersed smooth muscle cells to identify whether PTX-linked pathway mediated the contractility to bethanechol. RESULTS:A dose-dependent contractile response observed with bethanechol,was not affected by TTx.The pretreatment of rats with pertussis toxin decreased the contraction induced by bethanechol.Lack of calcium as well as the presence of the L-type calcium channel blocker,nifedipine,also inhibited the cholinergic contraction,with a reduction in response from 2.5±0.4 g/mm^2 to 1.2±0.4 g/mm^2(P<0.05).The dose- response curves were shifted to the right by muscarinic antagonists in the following order of affinity:darifenacin (M_3)>methocramine(M_2)>pirenzepine(M_1). CONCLUSION:The muscarinic receptors-dependent contraction of rat antral circular smooth muscles was linked to the signal transduction pathway(s)involving pertussis-toxin sensitive GTP-binding proteins and to extracellular calcium via L-type voltage gated calcium channels.The presence of the residual contractile response after the treatment with nifedipine,suggests that an additional pathway could mediate the cholinergic contraction.The involvement of more than one muscarinic receptor(functionally predominant type 3 over type 2)also suggests more than one pathway mediating the cholinergic contraction in rat antrum.

Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation.

Effects of glucagon-like peptide 1 analogs in combination with insulin on myocardial infarct size in rats with type 2 diabetes mellitus

AIM To evaluate the effects of glucagon-like peptide-1 analogs(GLP-1 a) combined with insulin on myocardial ischemiareperfusion injury in diabetic rats.METHODS Type 2 diabetes mellitus(T2 DM) was induced in maleWistar rats with streptozotocin(65 mg/kg) and verified using an oral glucose tolerance test. After anesthesia, the left coronary artery was occluded for 40 min followed by 80 min reperfusion. Blood glucose level was measured during surgery. Rats were randomized into six groups as follows:(1) control rats;(2) insulin(0.1 U/kg) treated rats prior to ischemia;(3) insulin(0.1 U/kg) treated rats at reperfusion;(4) GLP-1 a(140 mg/kg) treated rats prior to ischemia;(5) GLP-1 a(140 mg/kg) treated rats at reperfusion; and(6) rats treated with GLP-1 a(140 mg/kg) prior to ischemia plus insulin(0.1 U/kg) at reperfusion. Myocardial area at risk and infarct size was measured planimetrically using Evans blue and triphenyltetrazolium chloride staining, respectively.RESULTS There was no significant difference in the myocardial area at risk among groups. Insulin treatment before ischemia resulted in a significant increase in infarct size(34.7% ± 3.4% vs 18.6% ± 3.1% in the control rats, P < 0.05). Post-ischemic administration of insulin or GLP-1 a had no effect on infarct size. However, pre-ischemic administration of GLP-1 a reduced infarct size to 12% ± 2.2%(P < 0.05). The maximal infarct size reduction was observed in the group treated with GLP-1 a prior to ischemia and insulin at reperfusion(8% ± 1.6%, P < 0.05 vs the control and GLP-1 a alone treated groups).CONCLUSION GLP-1 a pre-administration results in myocardial infarct size reduction in rats with T2 DM. These effects are maximal in rats treated with GLP-1 a pre-ischemia plus insulin at reperfusion.

Apoptosis of Pancreatic Beta Cells in Pregnant Insulin-resistant Rats Fed with High-fat Diet

Objective The aim of this study is by observing the number change of islets beta cells in gestational rats exposed to high fat diet, tofurther reveal the mechanism of gestational diabetes mellitus. Methods Female Wistar rats were exposed to high fat diet for five weeks, and then became pregnant. During pregnancy dynamically detected indicators of glucose and fat. Until the third trimester of pregnancy evaluated the sensitivity of insulin and glucose tolerance. After executed rats, selected pancreatic tail tissue and fixed, further slides were stained with insulin antibody by immunohistochemistry to confirm the location of beta cells. Image analysis system determined mean area stained positive cells in each islet, which stood for total number of beta cells. The apoptotic beta cells in islet were detected and quantified by the Tunel technology to calculate apoptosis ratio. Results The level of free fatty acids in rats exposed to high fat diet was significantly higher than the control groups, and insulin resistance was more serious. Compared mean stained positive area among each group, the largest was gestational rats fed high fat diet, and gestational rats was larger than virgin rats, but the difference had no statistical significance. About apoptoticratio of beta cells was higher in diet intervened rats, gestational rats were higher than virgin rats. The same trend happened in the number of positive cells, but discrepancy was not remarkable. Conclusion Based on insulin resistance, apoptosis of pancreatic beta cellsincreased in gestational ratstaking high fat diet, through changing the number of beta cells to down regulate the pancreas endocrine function. That may be the mechanism of gestational mellitus.

Tail nerve electrical stimulation-induced walking training promotes restoration of locomotion and electrophysiology in rats with chronic spinal cord injury

Functional recovery is the final goal in the treatment of spinal cord injury. However, to date, few treatment strategies have demonstrated significant locomotor improvement in animal experiments. By using tail nerve electrical stimulation (TANES) as an open-field locomotor training method combined with glial scar ablation and cell transplantation, we have successfully promoted locomotor recovery in rats with chronic spinal cord contusion injury. The purpose of the present study is to further investigate the mechanism of TANES and its effect on electrophysiology. Spinal cord segment T10 of female, adult Long-Evans rats was contused using the NYU impactor device with 25 mm height setting. After injury, rats were randomly divided into three groups. Group I was used as a control without any treatment, group II and group III were subjected to basic treatment including glial scar ablation and transplantation of olfactory lamina propria 6 weeks after injury, and group III received TANES-induced open-field locomotor training weekly after basic treatment. All animals were allowed to survive 22 weeks, except some rats which were transected. Basso, Beattie, and Bresnahan (BBB) open-field locomotor rating scale, horizontal ladder rung walking test, and electrophysiological tests were used to assess the restoration of functional behavior and conduction. Results showed that TANES significantly improves locomotor recovery and spinal cord conduction, reflex, as well as significantly reduces the occurrence of autophagia. Additionally, after transection, trained rats still maintained higher BBB score than that of control rats. This may be related to the activity-dependent plasticity promoted by TANES-induced locomotor training.

The effect of traditional Chinese medicine“Tian Gui Recipe (TGR)”on obesity and anovulation in androgen-sterilized rats(ASR)

Objectives: A traditional Chinese medicine “Tian Gui Recipe (TGR)” has been used to effectively treat clomiphene resistant anovulatory disease and obesity, especially in polycystic ovary syndrome (PCOS) cases with hyperinsulinemia. The effect of TGR on obesity and anovulation was investigated in androgen-sterilized rats (ASR).Methods: Female SD rats at the age of 9 days were divided into 3 groups. Group ASR (n=15): anovulation was demonstrated at the age of 70 days by vaginal smear in rats while 1.25 mg of testosterone propionate was injected subcutaneously on its 9th neonatal day. Group A+H (n=25): TGR were administered to ASR at the age of 80 days for 3 weeks. Rats with regular estrous cycle and ovulation after herbal treatment were included in this group. Group C (n=15): normal ovulated rats were recruited. Around the age of 112 days or on proestrous day, all rats were sacrificed under anesthesia. Serum leptin, testosterone (T), estrogen (E2), follicular stimulating hormone (FSH), luteinizing hormone (LH) levels were measured with radioimmunoassay (RIA). Double immunofluorescent staining combined with confocal laser scanning microscope and dual in situ hybridization were carried out on sections through areas of arcuate nucleus (ARC) to determine whether estrogen receptor (ER) immunoreactivity (IR) or long form of leptin receptor (OB-Rb) mRNA were expressed in neuropeptide Y (NPY) immuno- and mRNA-containing neurons, and their relationship to proopiomelanocortin (POMC) mRNA-containing neurons. Immunohistochemistry and in situ hybridization were used to observe the levels of ER-, NPY-,gonadotrophin releasing hormone (GnRH)-IR and gene expression levels of NPY, OB-Rb, and POMC in ARC. Meanwhile, the criteria of energy state,including daily food intake, retroperitoneal fat depot pad and body weight,were measured and evaluated. Values of immunohistochemistry and in situ hybridization were expressed in mean optic density (MOD).Results:Seventeen out of the 25 rats (68%) in Group A+H were ovulated after herbal treatment. ASR characterized with significantly high metabolic rate, energy imbalance and obesity (P<0.01,P<0.01,P<0.01).The mean serum leptin, T, E2 levels of ASR were significantly higher than that of Group C and Group A+H (P<0.01,P<0.01), while being contraryto that of FSH, LH levels (P<0.01,P<0.01). ERs were proved distributing in NPY-containing neurons, OB-Rb coexpressed in NPY-synthesizing neurons, and both NPY- and POMC- mRNA expressing neurons overlapped in ARC. Compared to Group C, levels of NPY mRNA and NPY, POMC mRNA expressions increased (P<0.01,P<0.01,P<0.01),OB-Rb mRNA, ER and GnRH immunoreactive expression decreased significantly in the hypothalamus of ASR (P<0.01,P<0.01,P<0.01).These dramatic neuroendocrine changes became normal in ovulated ASR after the herbal treatment (all P>0.05).Conclusion: The elevated peripheral estrogen caused by high testosterone and leptin levels in ASR may down-regulate their corresponding receptors oriented on hypothalamic NPY-containing neurons respectively, therefore challenge the NPY mRNA and NPY,POMC mRNA overexpression. The overexpression of NPY, POMC gene transcription and translation stimulate food intake, promote the deposit of adipocyte tissue, and inhibit GnRH expression and GnRH/FSH, LH release, which contribute to the occurrence of obesity and anovulation in ASR. “TGR” may reverse these abnormal neuroendocrine cascades by lowering levels of testosterone, estrogen and leptin.

Transplantation of human hepatocytes into tolerized genetically immunocompetent rats

AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.

Protective effect of electroacupuncture and moxibustion on gastric mucosal damage and its relation with nitric oxide in rats

INTRODUCTION Gastric mucosal injury is one of the common disorders,there are many reports subjicted to its pathogenesis treatment and prevention.We investigated the protective effect

In vivo tracking of human adipose-derived stem cells labeled with ferumoxytol in rats with middle cerebral artery occlusion by magnetic resonance imaging

Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide ap- proved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-derived stem cells labeled with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in vivo. 1 × 104 human adipose-derived stem cells labeled with ferumoxytol-heparin-protamine were transplanted into the brains of rats with middle cerebral artery occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after transplantation. T2-weighted imaging and enhanced susceptibility-weighted angiography were used to observe transplanted cells. Results of imaging tests were compared with results of Prussian blue staining. The modified neurologic impairment scores were significantly lower in rats transplanted with cells at all time points except I day post-transplantation compared with rats without transplantation. Regions with hypointense signals on T2-weighted and enhanced susceptibility-weighted angiography images corresponded with areas stained by Prussian blue, suggesting the presence of superparamagnetic iron oxide particles within the engrafted cells. Enhanced susceptibility-weighted angiography image exhibited better sensitivity and contrast in tracing ferumoxytol-heparin-protamine-labeled human adipose-derived stem ceils compared with T2-weighted imaging in routine MRI.

Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had dis- appeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-medi- ated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraqnat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.

Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome

Objective:To investigate the effects of Uangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome induced by mutifactor stimuli.Methods:SD rats were divided into control, model,Uangxuehuayu Recipe(high,middle and low dose,18,9,4.S g/kg accordingly).Except the control group,blood stasis model was established in the rest groups.The hemorheological parameters were measured and compared.Results:Blood viscosity at high,moderate and low level in rats with blood stasis significantly increased(P【0.05),but blood viscosity at high level and plasma viscosity was significantly decreased in rats induced by some stimuli after Uangxuehuayu Recipe were intra-gastrically administered for I weeks(P【0.01,P【0.05). Conclusions:Uangxuehuayu Recipe is effective in improving hemorheology,and has important application value in the prevention of occurrence and development of ischemic stroke.

Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats

INTRODUCTIONLiver fibrosis is a dynamic course leading tocirrhosis from a various chronic liver diseases. Thepathological basis of fibrosis is the disturbance ofproduction and degradation of the extracellularmatrix (ECM), which causes accumulation of ECMin the liver[1,2].

Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats （7 days old） subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2＇-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2＇- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

Long-term acupuncture treatment has a multitargeting regulation on multiple brain regions in rats with Alzheimer＇s disease：a positron emission tomography study

The acute effect of acupuncture on Alzheimer＇s disease,i.e.,on brain activation during treatment,has been reported.However,the effect of long-term acupuncture on brain activation in Alzheimer＇s disease is unclear.Therefore,in this study,we performed long-term needling at Zusanli（ST36）or a sham point（1.5 mm lateral to ST36）in a rat Alzheimer＇s disease model,for 30 minutes,once per day,for 30 days.The rats underwent 18F-fluorodeoxyglucose positron emission tomography scanning.Positron emission tomography images were processed with SPM2.The brain areas activated after needling at ST36 included the left hippocampus,the left orbital cortex,the left infralimbic cortex,the left olfactory cortex,the left cerebellum and the left pons.In the sham-point group,the activated regions were similar to those in the ST36 group.However,the ST36 group showed greater activation in the cerebellum and pons than the sham-point group.These findings suggest that long-term acupuncture treatment has targeted regulatory effects on multiple brain regions in rats with Alzheimer＇s disease.

Chromosomal aberrations and nucleic acids systems affected by some Egyptian medicinal plants used in treating female pregnant diabetic rats

The influences of medicinal plants Juniperus Phoenicea (Araar), Hyphaene thebaica (Doum), An-astatica hierochuntica (Kafta) and Cleome droserifolia (Sammo) as antidiabetic agents were investigated using female pregnant albino rats. Female rats were injected with 60 mg/kg b.w. alloxan to induce diabe-tes. Diabetic rats treated orally with the methanol extracts of tested plants till the 19 day of gestation. The present studies include the frequencies of chro-mosomal aberrations and nucleic acid system of liver in the female pregnant rats and their embryos. The results showed that injection of alloxan caused highly significant increase in chromosomal aberrations as well as in blood glucose levels as a result of diabetes in pregnant females. It also caused a high incidence of chromosomal deviation in embryos and decreased the liver soluble protein contents of female rats and their embryos. These effects in alloxanized animals were treated and improved by ingestion of the methanol extracts of the tested plants (Araar, Doum, Kafta and Somma) in which under their treatments, the inceased level of blood glu-cose of diabetic rats was deceased. Ingestion with the plants methanolic extracts improved and normalized the effects of diabetes in nucleic acids values of liver tissues. These were accompanied with nucleases (RNAase and DNAase) activities. The inhibited ac-tivities of both DNA ase and RNA ase of pregnant rats and their embryos were stimulated and read-justed around the normal values. Also administration of the plants methanol extracts decreased the per-centage of chromosomal aberrations in the female rats and embryos. It is concluded that there are some biochemical dynamics which might occur in the metabo-lism of glucose, nucleic acids and proteins in order to prevent or to reduce the oxidative stress of diabetes by flavonoides treatment.

Regulatory Effect of Shenge Yifei Capsule on TGF-β1/Smad Signaling Pathway in Rats with Chronic Obstructive Pulmonary Disease

[Objectives]This study aimed to study the effects of Shenge Yifei capsule on the TGF-β1/Smad signaling pathway in rats with chronic obstructive pulmonary disease(COPD).[Methods]Ten rats were randomly selected as the control group,and the other 40 rats were selected for modeling by fumigation combined with Klebsiella pneumoniae infection.A total of 38 rats were successfully modeled.They were randomly divided into model group(8 rats),low-dose Shenge Yifei capsule group(10 rats),high-dose Shenge Yifei capsule group(10 rats)and theophylline group(10 rats)in accordance with the principle of half male and half female.The rats in the model and control groups were given with distilled water by gavage,and the rats in the drug administration groups were given with corresponding drugs.The TGF-β1 level in the serum,and the expression levels of TGF-β1,Smad2,Smad3 and Smad7 and TGF-β1,Smad3 and Smad7 in airway tissues were detected.[Results]After 12 weeks,the serum TGF-β1 levels of the theophylline group and high-dose Shenge Yifei capsule group were lower than that of the low-dose Shenge Yifei capsule group(P<0.05).The expression levels of TGF-β1 and Smad3 in the theophylline group and high-dose Shenge Yifei capsule group were lower than that in the low-dose Shenge Yifei capsule group(P<0.05).The expression levels of TGF-β1 and Smad3 in the high-dose Shenge Yifei capsule group were lower than those in the low-dose Shenge Yifei capsule group and theophylline group(P<0.05).The expression levels of Smad7 and the proteins in the model group were lower than those in the other groups(P<0.05).The expression levels of Smad7 in the theophylline group and high-dose Shenge Yifei capsule group were higher than that in the low-dose Shenge Yifei capsule group(P<0.05).After 18 weeks,no significant difference was found in serum TGF-β1 level among the theophylline group and low and high-dose Shenge Yifei capsule groups(P>0.05).The expression levels of Smad7 and the proteins in the model group were lower than those in the other groups.The expression level of Smad7 in the high-dose Shenge Yifei capsule group was lower than that in the theophylline group(P<0.05).[Conclusions]Shenge Yifei capsule can regulate the TGF-β1/Smads signaling pathway.They can down-regulate the expression of TGF-β1,Smad2 and Smad3 and up-regulate the expression of Smad7,reducing the degree of airway modeling,delaying the development of COPD disease.Conventional high-dose Shenge Yifei capsule is more effective in inhibiting the expression of Smad2.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.