Effects of total peony glucoside on cerebral Notch signaling pathway in focal cerebral infarction rats / 西安交通大学学报(医学版)

Objective: To investigate the effects of total paeony glucoside on brain Notch signaling pathway in focal cerebral infarction rats. Methods: Stroke rats were prepared and divided into 5 groups: model group, low dosetotal peony glucoside group, medium dosetotal peony glucoside group, and high dosetotal paeony glucoside group, with 20 rats in each group. All groups received the medication for 20 days. The body weight, brain water content, cerebral infarction size, brain tissue NICD, Hes1 and Hes5 proteins and Hes1 and Hes5 mRNA expressions were measured in each group. Results: There was no significant difference in body weight before administration within these groups (P>0.05). After treatment, compared with those in the control group, the body weight significantly decreased (P<0.05); NICD, Hes1 and Hes5 significantly increased; Hes1 and Hes5mRNA significantly increased in the model group (P<0.05). Compared with those in the model group, the body weight significantly increased (P<0.05); the NICD, Hes1 and Hes5 significantly decreased; Hes1 and Hes5mRNA significantly decreased (P<0.05) in a dose-dependent manner. Conclusion: Total peony glucoside can treat focal cerebral infarction by inhibiting Notch signaling pathway in rat brain tissue.

Effects of Exercise or Electroacupuncture Preconditioning on Neurological Deficits and Expression of Laminin in Rats with Cerebral Infarction / 中国康复理论与实践

Objective To investigate the effect of electroacupuncture or exercise preconditioning on neurological function after focal ce-rebral infarction in rats and the possible mechanism. Methods A total of 24 male Sprague-Dawley rats were randomly divided into model group (n=6), sham group (n=6), exercise preconditioning group (n=6) and electroacupuncture preconditioning group (n=6). The model group and the sham group did not accept any treatment, while the exercise preconditioning group and the electroacupuncture precondition-ing group accepted treadmill training and electroacupuncture for two weeks, respectively. Their middle cerebral arteries were occluded with modified Longa's approach, except the sham group that was ligated the same arteries but did not result in infarction. They were evaluated with Neurologic Severity Scores (NSS) 24 hours after modeling, and the laminin expression in the ischemic area was detected with Western blotting. Results There was no neurological deficit in the sham group. The NSS was lower in both preconditioning groups than in the model group (P0.05). The expression of laminin was the most in the sham group, and was more in both preconditioning groups than in the model group (P0.05). Conclusion Preconditioning with exercise or electroacupuncture can both reduce the neurological deficits in rats after focal cerebral infarction, which may associate with the protection of laminin from inhibition in early stage.

Retinoic acid protects from experimental cerebral infarction by upregulating GAP-43 expression

The aim of this study was to investigate whether exogenous retinoic acid (RA) can upregulate the mRNA and protein expression of growth-associated protein 43 (GAP-43), thereby promoting brain functional recovery in a rat distal middle cerebral artery occlusion (MCAO) model of ischemia. A total of 216 male Sprague Dawley rats weighing 300–320 g were divided into 3 groups: sham-operated group, MCAO+vehicle group and MCAO+RA group. Focal cortical infarction was induced with a distal MCAO model. The expression of GAP-43 mRNA and protein in the ipsilateral perifocal region was assessed using qPCR and immunocytochemistry at 1, 3, 7, 14, 21, and 28 days after distal MCAO. In addition, an intraperitoneal injection of RA was given 12 h before MCAO and continued every day until the animal was sacrificed. Following ischemia, the expression of GAP-43 first increased considerably and then decreased. Administration of RA reduced infarction volume, promoted neurological functional recovery and upregulated expression of GAP-43. Administration of RA can ameliorate neuronal damage and promote nerve regeneration by upregulating the expression of GAP-43 in the perifocal region after distal MCAO.

Effects of Huoxue Xifeng Decoction on Endothelin-1 and Nitric Oxide Levels of Focal Cerebral Infarction Rats / 中国中医药信息杂志

Objective To observe the effects of Huoxue Xifeng Decoction (HXD) on endothelin-1 (ET-1) and nitric oxide (NO) levels in the blood and brain tissue of focal cerebral infarction (FCI) rats. Methods Forty male Wistar rats were randomized into 5 groups:sham-operation, FCI model and HXD-high, HXD-middle, HXD-low dose groups, with 8 rats in each group. The model of FCI rats was established by photo-chemistry method, and intragastric administration were continue 7 days before operation. HXD-high, HXD-middle, HXD-low dose groups were given HXD 20, 10, 5 g/(kg?d) respectively, and other groups were given the same volume distilled water. Blood and brain tissue samples were gotten 24 h after operation, and radio-immunity method was used to measure ET-1 level, spectrophotometric method was used to measure NO level. Results Compared with FCI model group, HXD decreased ET-1 level in plasma and brain tissue after infarction, and decreased NO level in the brain tissue, increased NO level in serum (P

Effect of Reduced Glutathione on Expression of Malondialdehyde,Glutathione Peroxidase and Superoxide Dismutase after Focal Cerebral Infarction in Rats / 中国康复理论与实践

@#ObjectiveTo observe the effect of reduced glutathione(GSH) on expression of malondialdehyde(MDA),glutathione peroxidase(GSH-PX) and superoxide dismutase(SOD) after focal cerebral infarction in rats.MethodsRat models of middle cerebral artery occlusion(MCAO) were estabilished with thread after 2-hour ischemia and 6-hour reperfusion.Rats were divided at random into three groups,i.e.,sham-operated,control and treatment group(with GSH 1200 mg/kg) respectively.After the rats model was performed,neurology deficit score,the size of brain infarct region and the change of brain tissue pathologic were evaluated.Contents of MDA and activity of SOD and GSH-PX were detected with spectrophotometer.ResultsCompared with the control group,GSH can ameliorate neurological deficit score and decrease infarct volume induced by MCAO.GSH may reduce contents of MDA and improve activity of SOD and GSH-PX in brain tissue.ConclusionGSH may reduce contents of MDA and improve activity of SOD and GSH-PX so as to enhance capability of eliminating oxygen free radical,and play a neuroprotective effect after cerebral focal ischemia reperfusion.

Differences in p53 Protein Expression between Delayed and Completed Focal Cerebral Infarction in Rats

OBJECTIVE: We investigate and compare geometric patterns and degree of p53 protein expression in a peri-infarction area between two different types of cerebral infarction, delayed and completed focal cerebral infarctions. METHODS: For the delayed focal cerebral infarction group(Group 1 ; n=8), right middle cerebral artery(MCA) and bilateral common carotid artery(CCA) were ligated temporarily for thirty minutes, and their brains were obtained after 72 hours. For the completed focal cerebral infarction group(Group2 ; n=11), right MCA and CCA were occluded permanently, and contralateral CCA was occluded for thirty minutes, and their brains were obtained after 24 hours. RESULTS: The infarction volume was significantly larger in Group 2(267.2+/-29.6mm3) than that of Group 1(10.4+/-2.7mm3)(p<0.001). The width of p53 protein positive area was significantly longer in Group 1(107.8+/-60.5micro meter) than that in Group 2(75.0+/-7.1micro meter)(p<0.05). The density of p53 positive cell was more compact in group 2(48.2+/-1.7cells/HPF) than group 1(28.3+/-9.1cells/HPF)(p<0.001). CONCLUSION: It is suggested that the decreased p53 protein expression in the delayed infarction has certain roles other than apoptosis. The degree of p53 protein expression in the completed focal cerebral infarction seems to be closer to a critical level of gene expression that might determine cell death.

Influence of Brain Edema on the Antiischemic Effect of D-CPPene in Rat Focal Cerebral Infarction

OBJECTIVE: The model of focal ischemia that involves occlusion of middle cerebral artery(MCA) is one of the most commonly used methods in the rat, which can be considered to be equivalent to a focal cerebral infarction in man. Infarction size is often used as the standard to assess potential therapeutic regimens in models of focal cerebral infarction. In practice, scientists have estimated infarction volume by a variety of methods. One of the fundamental problems in measuring infarction volume is the enlargement of infarcted tissue by edema. To minimize the error of overestimation that may be caused by edema, several methods have been proposed. METHOD:The author assessed the antiischemic effect of a competitive N-methyl-D-aspartate(NMDA) antagonist, D-(E)-4-(3-phosphonoprop-2-enyl) piperazine-2carboxylic acid(D-CPPene) in MCA occlusion model in the rat. Four different morphometric analysis were used to measure infarction volume a real measurement, the Swanson's method designed to minimize the error of overestimation, a measurement using a diagram, percentage method (infarction volume divided by the volume of ipsilateral hemisphere), which were to elucidate the effects of each method upon measuring the infarction volume regarding the possible influence of edema. The animals were sacrificed 24 hours after MCA occlusion and the amount of ischemic brain damage was assessed by 8 predetermined coronal planes. RESULT: Post-occlusion treatment of D-CPPene which was initiated 15 minutes after MCA occlusion, produced reduction of infarction volume to about 40% compared to the control(p<0.05). The volume of infarction determined by a real measurement was much larger than that by the Swanson's or diagram method(p<0.05), about 70% larger in the control and 2 times larger in the treated group. However, there was no significant difference in the measured volume between the Swanson's and diagram methods. The protection rate which was obtained by subtracting the infarction volume of the treated from that of the control, was larger by the Swanson's and diagram method than by a real measurement and percentage method. CONCLUSION: These results demonstrate that a competitive NMDA antagonist, D-CPPene which was administered 15 minutes after post-occlusion, has a significant neuroprotective effect on ischemic brain damage in focal cerebral infarction. But it appears to have no specific protective effect on ischemic brain edema. The overestimation of infarction volume at the peak time of brain edema could be substantially reduced by not only the Swanson's method but also the diagram method.

Effect of Cervical Sympathectomy on Ischemic Brain Damage Induced by Focal Cerebral Infarction in Rats / 대한마취과학회지

BACKGROUND: Recently Umeyama et al. reported that cerebral blood flow is definitely increased on the ipsilateral side after the blockade of stellate ganglion. Considering that the most obvious solution to the problem of poor cerebral blood flow is to augment the flow, cervical sympathectomy may reduce the volume and extent of the brain damage by increasing the cerebral blood flow. We studied the effects of cervical sympathectomy on ischemic brain damage in a middle cerebral artery occlusion model in rats. METHOD: The experimental animals were divided into three groups. In the sham-operated control group (n=7), middle cerebral artery was occluded without cervical sympathectomy. In the experimental group I (n=7), cervical sympathectomy was performed 5 minutes before middle cerebral artery occlusion. In the experimental group II (n=7), cervical sympathectomy was performed 5 minutes after middle cerebral artery occlusion. The neurological grade of each experimental animal was evaluated at 24 hours post occlusion and then the animals were sacrificed. The brain was cut into coronal sections. The volume of infarct was computed and the edema volume was calculated. RESULTS: 1. There were no differences in the physiological variables in all groups. 2. Cervical sympathectomy, compared with the controls, significantly reduced the volume of infarct (P<0.05). 3. There was no significant difference in ischemic brain edema between each group. 4. The neurologic deficit was less severe in sympathectomized groups compared with the control group (P<0.05). And neurological grades were significantly correlated with the volume of infarction (P<0.05). CONCLUSION: These results suggest that cervical sympathectomy may improve the neurologocal deficit and reduce the infarct volume measured 24 hours following induction of focal cerebral infarction.

Therapeutic Effect of Postischemic Selective Brain Cooling on Ischemic Brain Damage and Edema in focal Cerebral Infarction

The present study investigates the effect of temporary selective brain cooling(SBC) on ischemic brain damage and edema on permanent middle cerebral artery(MCA) occlusion in the rat. Eighteen adult male Sprague-Dawley rats weighing 300-400g were used under halothane anesthesia. The brain temperature was monitored in the left caudate nucleus through a burr hole in the middle of the left coronal suture. All animals underwent left MCA occlusion via subtemporal approach. During the surgery, the physiological variables including mean arterial blood pressure were monitored continuously. Three groups of animals were studied: group 1. Normothermic brain themperature control(n=6) ; group 2, brain cooling for 30min(n=6) ; and group 3, brain cooling for 60min(n=6). In all groups, rectal temperature was maintaind 36.5 degrees C~37 degrees C, and in groups 2 and 3, brain temperature was lowered to less than 34 degrees C by active cooling. 15 min following MCA occlusion. After the brain cooling treatment, anesthesia was discontinued, and the animals were returned to the cage. Twenty-four hours following MCA occlusion, the rats were sacrificed. The volume of ischemic damage and edema was obtained by frozen section technique. There were no significant differences in all physiological parameters between normothermic and hypothermic animals, except the brain temperature. Postischemic SBC for either 30 or 60min significantly reduced the volume of infarction in the cerebral hemisphrere by 14%(p<0.05) or by 27%(p<0.01) respectively and also attenuated neurologic deficits observed at 24 hour postocclusion. However the volume of ischemic brain edema was not significantly reduced and the ratio of volume of brain edema/infarction increased signficantly in groups 2(p<0.05) and 3(p<0.05) compared with group 1. The present study demonstrates that postischemic temporary BSC can attenuate hemispheric infarction in a permanent focal cerebral ichemia model in the rat. However, ischemic brain edema appears not to be attenuated at all. The mechanisms of hypothermic protection and its clinical application are discussed.

Effect of Methylprednisolone on Ischemic Damage and Neurologic Deficit in Focal Cerebral Infarction in the Rat

Oxygen free radical-mediated lipid peroxidation has been implicated in the pathophysiology of various central nervous system injuries. Therapeutic use of methylprednisolone, a potent steroid and lipid peroxidation inhibitor, has been suggested in spinal cord and brain injuries. However, its neuroprotective effect against ischemic cell injury in cerebral ischemia still remains controversial. The present study was conducted to evaluate anti-ischemic effects of methylprednisolone in a middle cerebral artery occlusion model in rats. The experimental animals were divided into two group : The first group was vehicle-treated control(n=6), and the other was drug-treated group(n=6). In the drug-treated group, the animals received high doses of methylprednisolone(30 mg/kg of bolus followed by 5 mg/kg/h of maintenance dose) immediately after MCA coolusion until 24 hours post occlusion. Methylprednisolone did not exert any influence upon the physiological parameters during the surgery. However, the serum glucose level increased significantly during the survival period in the drug-treated animals(at 2 and 24 hours post occlusion : p0.1). Methylprednisolone did not improve neurologic deficits either. The present study demonstrates that high doses of methylprednisolone does not exert any bebeficial effect on the volume of ischemic damage in acute cerebral infarction, and secondary consequences of glucocorticoid-elevated serum glucose levels which may act to exacerbate ischemic lactic acidosis could be one of the mechanism of this negative effect.

Measurement of Regional Tissue Water and Ionic Concentrations During the Evolution of Infraction and the Therapeutic Value of Nimodipine in Rat Middle Cerebral Artery Occlusion Model of Ischemia

The evolution of infarction in the rat middle cerebral artery(MCA) occlusion model was examined by atomic absorption spectrometric measurements of Na, K and Ca concentrations in brain tissue sample. At 2, 4, 6, 8, and 24 hours after MCA occlusion and sham occlusion the brain tissue samples were obtained. Tissue water concentrations were estimated from dry-wet weight measurement. The effects of nimodipine(2 microgram/kg/min for 10 min) administered intra-venously at 4 hours(Group A), 6 hours(Group B), and 9 hours(Group C) after MCA occlusion were investigated on both the size of infarction and tissue water, Na, K, Ca concentrations at 24 hours. The result were as follows : 1) Normal concentrations of water, Na, K, and Ca averaged 0.793+/-0.009ml, 54.06+/-4.18 micromole, 81.04+/-3.44 micromole, and 3.578+/-0.712 micromole/gm wet weight. At the infarct site by 24 hours, the changes of tissue water and ionic concentrations were conspicuously evident so that water increased by more than 10%(p<0.005), Na increased by more than 120%(p<0.005), K decreased by more than 75%(p<0.005), and Ca increased by more than 200%(p<0.005). 2) The remarkable shifts of Na, K, and Ca concentrations occurred at 4-6 hours so that 60-85% of the ionic shifts developed by 6 hours. This characteristics of chronological ionic changes correlated well with the findings of 2% TTC staining during the evolution of infarction. Water concentrations increased rapidly at 2-4 hours so that nearly 80% of water shift developed by 4 hours. 3) In group A(administered at 4 hours), nimodipine treatment significantly reduced both the ionic shifts at the infarct site and the size of infarction compared with non-treated rats(p<0.05). 4) In group B(administered at 6 hours), nimodipine treatment did not significantly reduce the ionic shifts but did reduce the size of infarction compared with non-treated rats(p<0.05). In group C(administered at 8 hours), nimodipine treatment significantly reduce neither the ionic shifts nor the size of infarction. In summary it was concluded that the progressive changes in tissue water and ionic concentrations developed at the infarct sites and the critical period of the changes was between 4 and 6 hours, and nimodipine treatment was effective when administered within 4 hours. The results suggested that measurement of tissue ionic concentrations could be used as an alternative method for assessing tissue damage and a reliable method to quantify the tissue damage. This method may be useful for determining the time window for therapeutic protocol, as well as for evaluating therapeutic effects.