Total flavonoid of Litsea coreana leve exerts anti-oxidative effects and alleviates focal cerebral ischemia/reperfusion injury

In this study, we hypothesized that total flavonoid of Litsea coreana leve （TFLC） protects against focal cerebral ischemia/reperfusion injury. TFLC （25, 50, 100 mg/kg） was administered orally to a rat model of focal ischemia/reperfusion injury, while the free radical scavenging agent, edaravone, was used as a positive control drug. Results of neurological deficit scoring, 2,3,5-triphenyl tetrazolium chloride staining, hematoxylin-eosin staining and biochemical tests showed that TFLC at different doses significantly alleviated cerebral ischemia-induced neurological deficits and histopathological changes, and reduced infarct volume. Moreover, it suppressed the increase in the levels of nitrates plus nitrites, malondialdehyde and lactate dehydrogenase, and it diminished the reduction in glu- tathione, superoxide dismutase and catalase activities induced by cerebral ischemia/reperfusion injury. Compared with edaravone, the protective effects of TFLC at low and medium doses （25, 50 mg/kg） against cerebral ischemia/reperfusion injury were weaker, while the protective effects at high dose （100 mg/kg） were similar. Our experimental findings suggest that TFLC exerts neuroprotective effects against focal cerebral ischemia/reperfusion injury in rats, and that the effects may be asso- ciated with its antioxidant activities.

Immediate effects of scalp acupuncture with twirling reinforcing manipulation on hemiplegia following acute ischemic stroke: a hidden association study

Data mining has the potential to provide information for improving clinical acupuncture strategies by uncovering hidden rules between acupuncture manipulation and therapeutic effects in a data set. In this study, we performed acupuncture on 30 patients with hemiplegia due to acute ischemic stroke. All participants were pre-screened to ensure that they exhibited immediate responses to acupuncture. We used a twirling reinforcing acupuncture manipulation at the specific lines between the bilateral Baihui（GV20） and Taiyang（EX-HN5）. We collected neurologic deficit score, simplified Fugl-Meyer assessment score, muscle strength of the proximal and distal hemiplegic limbs, ratio of the maximal H-reflex to the maximal M-wave（Hmax/Mmax）, muscle tension at baseline and immediately after treatment, and the syndromes of traditional Chinese medicine at baseline. We then conducted data mining using an association algorithm and an artificial neural network backpropagation algorithm. We found that the twirling reinforcing manipulation had no obvious therapeutic difference in traditional Chinese medicine syndromes of ＂Deficiency and Excess＂. The change in the muscle strength of the upper distal and lower proximal limbs was one of the main factors affecting the immediate change in Fugl-Meyer scores. Additionally, we found a positive correlation between the muscle tension change of the upper limb and Hmax/Mmax immediate change, and both positive and negative correlations existed between the muscle tension change of the lower limb and immediate Hmax/Mmax change. Additionally, when the difference value of muscle tension for the upper and lower limbs was 〉 0 or 〈 0, the difference value of Hmax/Mmax was correspondingly positive or negative, indicating the scalp acupuncture has a bidirectional effect on muscle tension in hemiplegic limbs. Therefore, acupuncture with twirling reinforcing manipulation has distinct effects on acute ischemic stroke patients with different symptoms or stages of disease. Improved muscle tension in the upper and lower limbs, reflected by the variation in the Hmax/Mmax ratio, is crucial for recovery of motor function from hemiplegia.

Effects of tanshinone Ⅱ sodium sulfonate plus cinepazide maleate on the hemorrheologic indexes and blood lipids in patients with acute cerebral infarction

BACKGROUND： The severity of cerebral infarction is associated with the increase of blood viscosity caused by hyperfibrinogenemia and hyperlipidemia, etc. Thus it has become one of the target for treating cerebral infarction to decrease blood viscosity by integrated Chinese and western medicine. OBJECTIVE： To investigate the influence and clinical therapeutic effects of cinepazide maleate combined with tanshinone Ⅱ A sodium sulfonate on the hemorrheologic indexes and blood lipids of patients with acute cerebral infarction, and compare the results with those of simple cinepazide maleate treatment. DESIGN： A non-randomized case-controlled observation. SETTINGS： Hebei North University; the Second Affiliated Hospitals of Hebei North University; the Third Affiliated Hospitals of Hebei North University, PARTICIPANTS： Eighty-six inpatients with cerebral infarction were selected from the infirmary, the Second and Third Affiliated Hospitals of Hebei North University from September 2004 to October 2006. They were all diagnosed to have acute cerebral infarction by CT or MRI, and accorded with the diagnostic standards for acute cerebral infarction set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995. Meanwhile, 40 teachers and medical staff of voluntary physical examinees were selected as the control group. Informed contents were obtained from all the patients and their relatives. METHODS： The patients were divided into combined treatment group （n=43） and simple treatment group （n=3）. In the combined treatment group, the patients were administrated with 160 mg cinepazide maleate injection （Beijing Four-ring Pharmaceutical, Co.,Ltd, No. H200220125; 80 mg/2 mL） added in 5% glucose, and 40 mg tanshinone Ⅱ sodium sulfonate （Shanghai No.1 Biochemical ＆ Pharmaceutical Co.,Ltd., No. H31022558, 10 mg/2 mL） added in 250 mL normal saline. In the simple treatment group, the patients were only administrated with cinepazide maleate 320 mg added in 5% glucose or 250 mL normal saline. They were treated for 1 or 2 courses, once a day, and 14 days as a course. The patients were detected before treatment and at 14 and 28 days after treatment respectively. ① Determination of hemorrheologic indexes： Whole blood viscosity was determined with LBY-N6B automatic hemorrheologic meter; Plasma viscosity with LBY-F200B automatic plasma viscosity meter; Volume of fibrinogen was determined by the method of 12.5% sodium nitrate depositing biuret reaction. ② Determination of blood lipids： The serum levels of total cholesterol （TC）, triglyceride （TG）, low density lipoprotein cholesterol （LDL-C） and high density lipoprotein cholesterol （HDL-C） were determined. ③ Severity of neurological deficit： The total score of neurological deficit score （NDS） ranged from 0 to 45 points, 0 - 15 points was taken as mild, 16 - 30 points as moderate and 31 - 45 points as severe.④ Evaluation of curative effects： Generally cured： NDS decreased by 91% - 100%, and disabled severity of grade 0; Significantly improved： NDS decreased by 46% - 90%, and disabled severity of grades 1 - 3; Improved： NDS decreased by 18% - 45%; No change： NDS decreased by less than 18%; Aggravated： NDS increased by more than 18%. Generally cured and significant improved were taken as significant effect. ⑤ The adverse events and side effects after medication were observed. MAIN OUTCOME MEASURES： ① Results of hemorrheologic indexes and blood lipids; ② NDS results in the combined treatment group and simple treatment group; ③ Therapeutic effects and adverse events. RESULTS： All the 86 patients with cerebral infarction and 40 healthy controls were involved in the analysis of results. ① Results of hemorrheologic indexes and blood lipids： The hemorrheologic indexes and blood lipids before treatment were manifested as abnormalities to different extents in both the combined treatment group and simple treatment group; The hemorrheologic indexes after treatment were obviously improved in both groups. But the hemorrheologic indexes were improved more obviously in the combined treatment group as compared with those in the simple treatment group （P 〈 0.05）; The levels of TC, TG and LDL-C after treatment in the combined treatment group were obviously lowered （P 〈 0.05）, whereas those in the simple treatment group were not significantly changed （P 〉 0.05）. ② NDS results： The NDS scores at 14 and 28 days after treatment in the combined treatment group [（6.23±2.34）, （4.27± 1.83） points] were obviously lower than those in the simple treatment group [（8.76±3.41）, （6.65±2.49） points, P 〈 0.05]. ③ Therapeutic effects and side effects： The total significant effective rates in the combined treatment group and simple treatment group were 93% and 81% respectively. In the combined treatment group, 1 case suffered from palpitation, dizziness and agrypnia. In the simple treatment group, 1 case suffered from palpitation, dizziness and agrypnia, 1 case had itch of skin. All the above symptoms disappeared gradually after the transfusing speed was adjusted to be slower. No drug withdrawal occurred in the patients due to the adverse events. CONCLUSION： Cinepazide maleate combined with tanshinon can obviously improve the abnormalities of hemorrheologic indexes and blood lipids and nerve function in patients with acute cerebral infarction, and its curative effect is faster than that of simple cinepazide maleate treatment.

Effect of post-stroke sensory disorders on the recovery processes of motor function and activity of daily living A non-randomized synchronical controlled trial

BACKGROUND： In the rehabilitation of stroke patients, clinicians usually concentrate on motor problems, such as spasm of limbs and restriction of joint motion, while sensory and perceptive problems are almost always neglected, although they are just as important. One such area is the sensory disorder. OBJECTIVE： To evaluate the motor function and activities of daily living in stroke patients with and without sensory disorders after treatment of integrated western and Chinese medicine. DESIGN： A non-randomized synchronically controlled trial. SETTING： First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine. PARTICIPANTS： Totally 500 stroke inpatients were selected from the Department of Acupuncture and Massage, the First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine from January 2003 to December 2004. They all had suffered from stroke in the last 4 weeks and accompanied by sensory disorder of the ipsilateral limb to different severity. The patients were all accorded with the Diagnostic and Efficacy Evaluative Standards for Stroke （in trial） set by the Encephalopathy Emergency Assistant Group, the State Administration of Traditional Chinese Medicine in 1995, and they were diagnosed by imaging examination. The patients were stratified into sensory disorder group （n =220） and normal sense group （n =280）. Informed consent for the detected items and therapeutic program was obtained from the relatives of all the participants. The study was approved by the hospital ethical committee. METHODS： All the patients were treated with acupuncture of Xing Nao Kai Qiao for restoring consciousness and inducing resuscitation, assisted by traditional Chinese medicine and western medicine specific to corresponding symptoms. The therapeutic principles were restoring consciousness and inducing resuscitation, nourishing liver and kidney, and dredging meridian. In addition, the patients were given western medical treatments for decreasing intracranial pressure, thrombolysis, reducing blood viscosity, anticoagulation, anti-arteriosclerosis, ameliorating microcirculation, also administrated with activator for nerve cells. MAIN OUTCOME MEASURES： （1） The severity of motor function deficit was evaluated using clinical neurological deficit score for stroke patients set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995; （2） The activities of daily living was evaluated with Barthel Index, the higher the score, the better the independence, and the less the dependence. RESULTS： All the 500 stroke patients were involved in the final analysis of results. （1） The neurological deficit scores before treatment had no significant difference between the two groups （P 〉 0.05）, but the scores after treatment were significantly decreased as compared with those before treatment in both groups （t =6.59, 12.43, P 〈 0.01）. The neurological deficit score after treatment in the normal sense group was significantly lower than that in the sensory disorder group （t =1.63, P 〈 0.05）. （2） The scores of activities of daily living after treatment were significantly increased as compared with those before treatment in both groups （t =16.03, 25.10, P 〈 0.01）. The scores of activities of daily living in the normal sense group were higher than those in the sensory disorder group both before and after treatment （t =6.07, 14.26, P 〈 0.05）. CONCLUSION： Sensory disorders have obvious negative effects on the recovery of motor function and activities of daily living of stroke patients.

CLINICAL STUDY ON TREATMENT OF ACUTE ISCHEMIC STROKE WITH ACUPUNCTURE OF ACUPOINTS OF THE PERICARDIUM MERIDIAN AND THE HEART MERIDIAN

Objective: To research the protective effect of acupuncture on the cardiac performance and cerebral function in acute ischemic stroke (AIS) patients. Methods: Forty AIS patients were randomly divided into acupuncture group (n=20) and medication group (n=20) according to their admission sequence. Acupoints, bilateral Neiguan (PC 6) and Tongli (HT 5) were punctured with Gauge-28 filiform needles, once daily, with 10 sessions being a therapeutic course. Patients of the medication group were treated with oral administration of persantine and aspirin as well as intravenous drip of 20% mannitol, low molecular dextran and compound Danshen (red sage root) injectio. Cerebral infarction volume, ECG (heart rate, ST Ⅱ and T Ⅱ), plasma CGRP, thromboxane (TX) B 2 and 6-Keto-prostanglandin (PG) F1a and scores of the neurological deficit were used as the indexes. Results: After 2 courses of treatment, self comparison of pre-and post treatment of each group showed that the therapeutic effects of acupuncture in reducing infarction volume ( P<0.01), lowering heart rate (HR, P<0.01) and ST Ⅱ ( P<0.01), raising T Ⅱ wave amplitude ( P<0.01), elevating plasma CGRP ( P<0.001) and 6-keto-PGF 1a ( P<0.01) and reducing plasma TXB 2 ( P< 0.01) were superior to those of medication group. Conclusion: Acupuncture of acupoints of the Pericardium Meridian and Heart Meridian has a significant protective action on the cardiac performance and cerebral function in acute ischemic stroke patients.

Therapeutic time window of flurbiprofen axetil＇s neuroprotective effect in a rat model of transient focal cerebral ischemia

Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.

Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

Background Our previous papers indicate that flurbiprofen axetil （FA）, a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y （PPAR-y） after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley （SD） rats were randomly assigned into six groups （n=8 in each group）： animals in group ischemia/reperfusion （I/R） only received 120-minute transient middle cerebral artery occlusion （tMCAO）; animals in group I/R ＋FA were administered FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋FA＋GW9662 were administered GW9662 （a PPAR-Y inhibitor, 1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset and FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋GW9662 were administered GW9662 （1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R ＋DMSO were administered 3% DMSO （vehicle of GW9662, 1 ml/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score （NDS） were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） 10 g/L staining. Results NDS was significantly increased in group I/R＋FA （12.0 （10.0-15.0））, group I/R＋FA＋GW9662 （10.0 （8.0-12.0））, and in group I/R＋FA＋DMSO （12.0 （9.0-14.0）） at 72 hours after reperfusion compared with those in group I/R （7.5 （6.0-10.0））. NDS was conspicuously different between group I/R＋FA （12.0 （10.0-15.0）） and group I/R＋FA＋GW9662 （10.0 （8.0-12.0））. MBIVP in group I/R （（45.82±8.83）%） was significantly greater than that in group I/R＋FA （（23.52±9.90）%）, group I/R＋FA＋GW9662 （（33.17±7.15）%）; MBIVP in group I/R＋FA （（23.52±9.90）%） was significantly smaller than that in group I/R＋FA＋GW9662 （（33.17±7.15）%）. Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.