PURPOSE: This study was done to identify whether pre-conditioning exercise has neuroprotective effects against cerebral ischemia, through enhance brain microvascular integrity. METHODS: Adult male Sprague-Dawley rats were randomly divided into four groups: 1) Normal (n=10); 2) Exercise (n=10); 3) Middle cerebral artery occlusion (MCAo), n=10); 4) Exercise+MCAo (n=10). Both exercise groups ran on a treadmill at a speed of 15 m/min, 30 min/day for 4 weeks, then, MCAo was performed for 90 min. Brain infarction was measured by Nissl staining. Examination of the remaining neuronal cell after MCAo, and microvascular protein expression on the motor cortex, showed the expression of Neuronal Nuclei (NeuN), Vascular endothelial growth factor (VEGF) & laminin. RESULTS: After 48 hr of MCAo, the infarct volume was significantly reduced in the Ex+MCAo group (15.6+/-2.7%) compared to the MCAo group (44.9+/-3.8%) (p<.05), and many neuronal cells were detected in the Ex+MCAo group (70.8+/-3.9%) compared to the MCAo group (43.4+/-5.1%) (p<.05). The immunoreactivity of laminin, as a marker of microvessels and Vascular endothelial growth factor (VEGF) were intensively increased in the Ex+MCAo group compared to the MCAo group. CONCLUSION: These findings suggest that the neuroprotective effects of exercise pre-conditioning reduce ischemic brain injury through strengthening the microvascular integrity after cerebral ischemia.
Animals ; Brain Infarction/pathology ; Disease Models, Animal ; Infarction, Middle Cerebral Artery/metabolism/pathology/*prevention & control ; Laminin/metabolism ; Male ; Microvessels/metabolism ; Neurons/metabolism ; *Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Stroke/prevention & control ; Vascular Endothelial Growth Factor A/metabolism

It has been suggested that propofol has the protective effect on cerebral ischemia-reperfusion injury. The aim of this study is to evaluate the effect of propofol pretreatment on incomplete forebrain ischemia-reperfusion injury in rats. Thirty Sprague-Dawley rats were anesthetized with isoflurane in oxygen and randomly allocated into propofol group (n=13) and saline group (n=17). In propofol group, propofol was pretreated in a step-down scheme before inducing forebrain ischemia by occlusion of both common carotid arteries and arterial hypotension. After ischemia (20 min) and reperfusion (30 min), rats were decapitated. Brain was sliced to obtain coronal slices of 4-12 mm from frontal pole, which were reacted with 2% 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) for 10 min to differentiate the damaged tissues from normal tissues. Median (interquartile range) values of the average percent infarct area were 0.0 (8.6)% and 20.1 (41.2)% in propofol and saline groups, respectively. There was significant difference between the groups. In conclusion, propofol may have a protective effect on incomplete forebrain ischemia-reperfusion injury.
Animal ; Brain Ischemia/prevention & control* ; Brain Ischemia/pathology ; Cerebral Infarction/prevention & control ; Cerebral Infarction/pathology ; Disease Models, Animal ; Free Radical Scavengers/pharmacology* ; Mitochondria/enzymology* ; Neuroprotective Agents/pharmacology* ; Oxidative Phosphorylation ; Propofol/pharmacology* ; Prosencephalon/metabolism ; Prosencephalon/injuries ; Prosencephalon/drug effects* ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/prevention & control* ; Reperfusion Injury/pathology ; Tetrazolium Salts

OBJECTIVETo investigate the protective effect of leptin against cerebral ischemia/reperfusion injury in mice.

METHODSMouse models of transient focal cerebral ischemia were established by occlusion of the right middle cerebral artery for 2 h followed by 24 h reperfusion. The infarct volume and neurological deficit scores following leptin treatment were determined using TTC staining and the Longa's score, respectively, to evaluate the protective effect of leptin against ischemic cerebral injury. The levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and nitric oxide (NO) in the brain tissue were measured by colorimetry. The histopathological changes in the brain were observed with HE staining, and the expression of glial fibrillary acidicprotein (GFAP) was detected by immunohistochemistry.

RESULTSLeptin treatment markedly reduced cerebral infarct volume and neurological deficits induced by transient ischemia. The LDH, MDA and NO levels in the brain tissues were significantly decreased after leptin treatment, which also alleviated the histopathological injury, maintained the normal morphology of the astrocytes and increased the expression of GFAP.

CONCLUSIONLeptin produces obvious protective effect against cerebral ischemia/reperfusion injury by inhibiting lipid peroxidation, stabilizing the internal environment and adjusting the activity of the astrocytes.

Animals ; Brain ; drug effects ; pathology ; Brain Ischemia ; Infarction, Middle Cerebral Artery ; metabolism ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Leptin ; pharmacology ; Male ; Malondialdehyde ; metabolism ; Mice ; Nitric Oxide ; metabolism ; Reperfusion Injury ; metabolism ; pathology ; prevention & control ; Time Factors

AIMTo study the effect of 3,4-oxo-isopropylidene-shikimic acid (ISA) against arteriovenous shunt and middle cerebral artery thrombosis (MCAT) in rats.

METHODSArteriovenous shunt model was adopted to measure thrombus weight; The neurologic deficit (ND) and the infarct size (IS) of the middle cerebral thrombosis (MCAT) model induced by FeCl3 were observed; The effect of ISA on platelet aggregation rate of rat and rabbit by giving ISA in vivo and in vitro was studied.

RESULTSISA 25, 50, 100 and 200 mg.kg-1 ig was shown to reduced the weight of thrombus in arteriovenous shunt model; ISA 50, 100 and 200 mg.kg-1 ig for 2 times in 24 hours, attenuated the ND of rats subjected to MCAT; ISA 100 and 200 mg.kg-1 reduced IS of rats after MCAT by 27.8% and 31.6%, respectively; ISA 50, 100 and 200 mg.kg-1 ig inhibited platelet aggregation of normal rats; ISA 10(-3)-10(-5) mol.L-1, inhibited rabbit platelet aggregation in vitro.

CONCLUSIONISA inhibited thrombosis by anti-platelet-aggregation.

Animals ; Brain ; pathology ; Disease Models, Animal ; Fibrinolytic Agents ; pharmacology ; therapeutic use ; Infarction, Middle Cerebral Artery ; blood ; pathology ; prevention & control ; Male ; Platelet Aggregation ; drug effects ; Rabbits ; Random Allocation ; Rats ; Rats, Wistar ; Shikimic Acid ; analogs & derivatives ; chemistry ; isolation & purification

OBJECTIVETo tentatively establish a diagnosis and treatment mode for effectively controlling the progress of cerebral microlesions (CM) and preventing the incidence of cerebral infarction (CI) by comparing different intervention modes for treating CM.

METHODSUsing a prospective, nonrandomized, controlled trial, 408 subjects with multiple CM were assigned to the Chinese medical pharmacy intervention group (Group A, 100 case), the aspirin intervention group (Group B, 104 cases), the negative control group (Group C, 100 cases), and the non-intervention group (Group D, 104 cases). No intervention was given to those in Group D. Patients in the other 3 groups were intervened by life style and routine therapies of vasculogenic risk factors. Those in Group A took Guizhi Fuling Pill (GFP) and earthworm powder additionally. Those in Group B took aspirin additionally. They were routinely followed-up. The CM, the changes of vasculogenic risk factors, and the incidence rate of CI were compared among the 4 groups.

RESULTSThe total effective rate of CM was 66.67% in Group A, obviously higher than that of Group B (52.32%), Group C (42.86%), and Group D (37.04%), respectively. It was obviously higher in Group B than in Group D, showing statistical difference (P <0.01, P <0.05). After treatment, the serum levels of LDL-C, TC, and TG were obviously lower in Group A than in Group B (P <0.05); the serum levels of LDL-C and TC were obviously lower in Group A than in Group C (P <0.01); the systolic pressure was obviously lower in Group A than in Group D (P <0.05). The systolic pressure and the serum TC level were obviously lower in Group C than in Group D (P <0.05). The incidence rate of CI was 2.17% (2/92 cases) in Group A, obviously lower than that of Group C (11.36% ,10/88 cases) and Group D (14.44%, 13/90 cases), showing statistical difference (P <0.05). But there was no statistical difference between Group A and Group B (6.74% ,6/89 cases) (P >0.05).

CONCLUSIONSGFP combined earthworm powder could treat CM, control vasculogenic risk factors, and finally prevent the incidence of CI. Standard Chinese medical intervention mode showed the optimal effects in treating CM and preventing the incidence of CI, and perhaps it could be spread clinically.

Adult ; Aged ; Aged, 80 and over ; Aspirin ; therapeutic use ; Brain ; pathology ; Cerebral Infarction ; drug therapy ; pathology ; prevention & control ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy ; Prospective Studies ; Risk Factors ; Treatment Outcome

PURPOSE: This study was undertaken to determine the neuroprotective effect of granulocyte stimulating factor (G-CSF) on neonatal hypoxic-ischemic brain injury. MATERIALS AND METHODS: Seven-day-old male newborn rat pups were subjected to 110 minutes of 8% oxygen following a unilateral carotid artery ligation. Apoptosis was identified by performing terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining and flow cytometry with a combination of fluorescinated annexin V and propidium iodide (PI) and JC-1 (5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide). The extent of cerebral infarction was evaluated at 2 weeks after recovery. RESULTS: With a single dose (50microgram/kg) of G-CSF treatment immediately after hypoxic-ischemic insult, hypoxia-ischemia induced increase in TUNEL-positive cells, annexinV+/PI- and JC-1 positive apoptotic cells in the ipsilateral cerebral cortex was significantly reduced at 24 hours, measured by flow cytometry, and the extent of cerebral infarction at 2 weeks after recovery was also significantly attenuated compared to the hypoxia-ischemia control group. CONCLUSION: Our data suggest that G-CSF is neuroprotective by inhibiting apoptosis, thereby reducing the ensuing cerebral infarction in a newborn rat pup model of cerebral hypoxia-ischemia (HI).
Animals ; Apoptosis/*drug effects ; Brain/pathology ; Cerebral Infarction/pathology/prevention & control ; Flow Cytometry ; Granulocyte Colony-Stimulating Factor/*pharmacology/therapeutic use ; Hypoxia-Ischemia, Brain/*drug therapy/pathology ; In Situ Nick-End Labeling ; Male ; Organ Size ; Protective Agents/*pharmacology/therapeutic use ; Rats ; Rats, Sprague-Dawley ; Weight Gain

OBJECTIVETo study the protective effect of ligusticum chuanxiong phthalides on cerebral ischemia in rats and its related mechanism of action.

METHODMiddle cerebral artery occlusion (MCAO) model, thrombosis formation, platelet aggregation and hemorrheological parameters were measured to evaluate the protective effect of ligusticum chuanxiong phthalides.

RESULTLigusticum chuanxiong phthalides could markedly decrease the infarct size and behavior deficits score, inhibit the thrombus formation and platelet aggregation, ameliorate hemorrheological parameters with a dose-dependent manner in rats.

CONCLUSIONLigusticum chuanxiong phthalides has protective effects on focal cerebral ischemia in rats, and its mechanism may be relevant to its inhibition of platelet-dependent thrombosis and amelioration of hemorrheological parameters.

Animals ; Benzofurans ; isolation & purification ; pharmacology ; Blood Viscosity ; drug effects ; Brain Ischemia ; blood ; pathology ; Dose-Response Relationship, Drug ; Hematocrit ; Infarction, Middle Cerebral Artery ; blood ; pathology ; Ligusticum ; chemistry ; Male ; Neuroprotective Agents ; pharmacology ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Rats ; Rats, Wistar ; Venous Thrombosis ; prevention & control

OBJECTIVETo investigate the effects of caffeic acid ester fraction (Caf) from Erigeron breviscapus, mainly composed of dicaffeoylquinic acids (diCQAs), on microglial activation in vitro and focal cerebral ischemia in vivo.

METHODSThe production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) induced by lipopolysaccharide (LPS) treatment in rat primary cultured microglia were measured by Griess reaction or enzyme-linked immunosorbent assay. Cell viability of cortical neurons was measured using AlamarBlue reagent. The behavioral tests and the infarct area of brain were used to evaluate the damage to central nervous system in rat middle cerebral artery occlusion (MCAO) model of cerebral ischemia. Real time polymerase chain reaction was used to determine the expression of inducible nitric oxide synthase (iNOS), TNF-α and IL-1β mRNA in ischemic cerebral tissues.

RESULTSCaf inhibited the production of NO, TNF-α and IL-1β induced by LPS treatment in primary microglia in a dose-dependent manner. Exposure of cortical neurons to conditioned medium from Caf-treated microglia increased neuronal cell viability (P<0.01) compared with conditioned medium from LPS-treated alone. In MCAO rat model of cerebral ischemia, Caf could significantly improve neurobehavioural performance and reduce percentage infarct volume compared with the vehicle group (P<0.05). Caf could also significantly inhibit the up-regulation of iNOS, TNF-α, and IL-1β gene expressions in ischemic cerebral tissues.

CONCLUSIONCaf could suppress microglial activation, which may be one mechanism of its neuroprotective effect against ischemia.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Brain Ischemia ; complications ; drug therapy ; pathology ; prevention & control ; Caffeic Acids ; chemistry ; pharmacology ; Chemical Fractionation ; Chromatography, High Pressure Liquid ; Erigeron ; chemistry ; Gene Expression Regulation ; drug effects ; Infarction, Middle Cerebral Artery ; complications ; pathology ; Interleukin-1beta ; genetics ; metabolism ; Microglia ; drug effects ; metabolism ; pathology ; Neuroprotective Agents ; chemistry ; pharmacology ; therapeutic use ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Plant Extracts ; pharmacology ; Quinic Acid ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

OBJECTIVETo observe the effect of Yirong Oral Liquid (YROL) on reperfusion injury in rats with cerebral infarction undergoing thrombolysis.

METHODSClinical reperfusion under thrombolysis was simulated by applying thrombolysis on reversible local cerebral ischemic rat model. In the rat model, effect of YROL on parameters concerning anti-oxidation capability, cerebral edema and ultrastructure of brain were observed.

RESULTSYROL could alleviate the cerebral edema after reperfusion, markedly increase the activity of superoxide dismutase in blood plasma, decrease the content of malonyldialdehyde, inhibit the post-reperfusion lipid peroxidation, and significantly reduce the ischemia/reperfusion injury of nerve cells in brain of rat.

CONCLUSIONYROL has definite protecting effect on brain.

Animals ; Cerebral Infarction ; drug therapy ; pathology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Malondialdehyde ; blood ; Neuroprotective Agents ; therapeutic use ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Superoxide Dismutase ; blood ; Thrombolytic Therapy ; Urokinase-Type Plasminogen Activator ; therapeutic use

OBJECTIVETo observe the effect of cyclovirobuxinum-D (CVB-D) on cerebral ischemia-reperfusion injury in rats and explore its mechanisms.

METHODOne hundred and twenty rats were randomly divided into three CVB-D groups (2, 1, 0.5 mg x kg(-1)), Nimodipine group (2 mg x kg(-1)), model group and sham operated group, 20 rats each group. Rat cerebral ischemia-reperfusion injury model was induced by middle cerebral artery occlusion, the nerve injury symptoms was evaluated, the level of SOD and MDA in brain tissue were determined, the concentration of intracellar Ca2+ of brain was measured, and the pathological change of brain was also observed.

RESULTCVB-D could improve the nerve injury symptoms, reduce the infarction area of brain, the concentration of intracellar Ca2+ and the level of MDA, increase the activity of SOD, and decrease the pathological change of brain.

CONCLUSIONCVB-D has protective effect on cerebral ischemia-reperfusion injury in rats.

Animals ; Brain ; drug effects ; metabolism ; pathology ; Buxus ; chemistry ; Calcium ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Infarction, Middle Cerebral Artery ; complications ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; etiology ; metabolism ; prevention & control ; Superoxide Dismutase ; metabolism