Research Related to Neural Protection of Hypoxic and Hyperoxic Preconditioning after Spinal Cord Injury (review) / 中国康复理论与实践

Repeated acute intermittent hypoxia promotes the expression of growth factors and neurotrophic factors, as well as the key molecules for neural protection and plasticity. Hypoxic preconditioning may improve the survival rate of transplant-ed stem cells and protect the neural function. Meanwhile, acute intermittent hypoxia can be an approach to improve re-spiratory function after spinal cord injury. Hyperbaric oxygen may improve the neural tolerance to hypoxia and isch-emia, to protect the structure of cells and tissues, and promote the neuranagenesis. It is important to study the role of hy-poxic and hyperoxic preconditioning in spinal cord injury.

Role of BDNF-trkB signaling pathway in ketamine treating diabetic neuropathic pain / 中国药理学通报

Aim Toinvestigatetheroleofbrain-de-rived neurotrophic factor(BDNF)-tyrosine receptor ki-nase B (trkB ) signaling pathway in the therapeutic effects of ketamine on diabetic neuropathic pain.Meth-ods Forty-eightWistarrats,aged3months,weighing 200~250 g,were equally randomized into 4 groups(n=12 ):control group (C group ), saline group (S group),ketamine group (K group)and ketamine +ANA-12 group (KA group ).Rats in S,K and KA groups were intraperitoneally injected with a single of streptozotocin(STZ)65 mg·kg-1 to construct diabetic neuropathic pain model.After twenty-eight days,rats in S,K and KA groups were intraperitoneally injected with saline, ketamine 10 mg·kg-1 and ketamine 10 mg·kg-1 +ANA-12 0. 5 mg·kg-1 for consecutive 7 days, respectively. On the 8th day, mechanical withdrawal threshold(MWT)of rats was measured.Af-ter that,the rats were immediately sacrificed,and dor-sal ganglion of lumbar spine and prefrontal cortex (PFC)were harvested for measuring BDNF,p-trkB/trkB,synaptophysin and spine density by Western blot andglogistaining.Results ComparedwithCgroup, rats in S group significantly decreased MWT,BDNF, p-trkB/trkB,synaptophysin and spine density in dorsal ganglion and PFC (P <0. 05 ).Compared with S group,rats in K group showed a significant increase of MWT,BDNF,p-trkB/trkB,synaptophysin and spine density in the all observed regions(P<0. 05 ).On the contrary,rats in KA group showed a significant de-crease of MWT and BDNF,p-trkB/trkB,synaptophys-in and spine density as compared with K group in all regions(P<0. 05 ).Furthermore,BDNF was positive-ly correlated with spine density in all regions (P <0.05).Conclusion BDNF-trkBsignalingpathway mediates ketamine-induced therapeutic effects in dia-betic neuropathic pain.

Analysis of clinical evaluation of response to treatment of Parkinson's disease with integrated Chinese and Western medicine therapy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To analyze the clinical evaluation of Parkinson's disease (PD) patients receiving integrated Chinese and Western medicine therapy.</p><p><b>METHODS</b>One hundred and twenty patients were enrolled and randomly allocated to a control group or treatment group. Patients in the two groups received placebo and Bushen Huoxue Granule (, BHG), respectively. Both groups received baseline levodopa and benserazide (Madopar). The effects of treatment were assessed monthly during the 9-month treatment. Means of evaluation included Unified PD Rating Scale (UPDRS) scores (II and III), sleep scale score, 10 m turn back test (getting up time, 10 m×2 times, and turning time), timing motor test (TMT)-left and TMT-right, which were treated as the dependent variables; and age, sex, duration of PD, Hoehn and Yahr (H-Y) stage and Madopar dosage of admitted PD patients were as the independent variables. Multiple linear regression was used to analyze these factors.</p><p><b>RESULTS</b>H-Y stage significantly affected UPDRS II score, UPDRS III score, and getting up time (P<0.01). Madopar dosage and H-Y stage significantly affected the 10 m×2 times (P<0.05 or <0.01). Madopar dosage significantly affected the sleep scale score (P<0.05). There were also significant correlations between age and TMT-left or TMT-right (P<0.01), and duration of PD and TMT-right (P<0.05).</p><p><b>CONCLUSIONS</b>The six assessed means of clinical evaluation (including UPDRS II and UPDRS III scores, sleep scale score, getting up time, 10 m×2 times, and turning time) are sensitive indexes in all PD patients. H-Y stage and Madopar dosage are the major factors influencing means of clinical assessment of PD treatment.</p>

Recurrence of Cerebral Infarction Associated Aspirin Resistance or Chinese Medical Constitutions: a Correlation Study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the correlation between the recurrence of cerebral infarction and aspirin resistance (AR)/Chinese medical (CM) constitutions.</p><p><b>METHODS</b>Totally 413 cerebral infarction patients took Aspirin Enteric-coated Tablet (100 mg per day) while receiving routine therapy, 5 days at least in a week. They were followed-up for 12 months. Aspirin sensitivity (AS) was determined using turbidimetry. CM constitutions among patients with different AS were compared. Ratios of AR patients and AS patients of different CM constitutions in cerebral infarction recurrent patients were compared. Platelet membrane glycoproteins (GP) II b HPA-3 gene polymorphism was detected by polymerase chain reaction (PCR) method. Correlation between recurrence of cerebral infarction and AR, bb genotypes, CM constitutions times AS were analyzed by Logistic regression.</p><p><b>RESULTS</b>Totally 11 patients dropped out, 101 (25.12%)with recurrent cerebral infarction and 301 (74.88%) without recurrent cerebral infarction. There were 152 (37.81%) AR patients and 250 (62.19%) AS patients. AR accounted for 26.6% (80/ 301) and AS accounted for 73.4% (221/301) in non-recurrent cerebral infarction patients. AR accounted for 71.3% (72/101) and AS accounted for 28.7% (29/101) in recurrent cerebral infarction patients. There was statistical difference in AR and AS ratios (χ2 = 64.287, P = 0.000). The proportion of yin deficiency constitution (YDC) was the largest [28.3% (43/152)] in AR patients. The proportion of blood stasis constitution (BSC) was the largest [23.6% (59/250)] in AS patients. There was statistical difference in CM constitutions between AR patients and AS patients (χ2 = 21.574, P < 0.01). The former 4 recurrent rates occurred in AR patients of YDC, BSC, damp-phlegm constitution (DPC), qi deficiency constitution (QDC). YDC occupied the first place [22.4% (34/152)]. The former 4 recurrent rates occurred in AS patients of BSC, QDC, DPC, damp-heat constitution (DHC). BSC occupied the first place [3.2% (2/250)]. Compared with non-recurrent cerebral infarction patients and AS patients, bb gene occurred most often, but aa gene and ab gene occurred obviously lesser in non-recurrent cerebral infarction patients and AR patients (χ2 = 20.171, χ2 = 55.139, P < 0.01). AR and bb gene were positively correlated with recurrent cerebral infarction (OR = 18.423, P = 0.000; OR = 1.304, P = 0.028). Body constitutions interacted with AS (OR = 0.707, P = 0.000).</p><p><b>CONCLUSIONS</b>Recurrent cerebral infarction was closely related to AR and constitutional types. The recurrence rate was higher in AR patients of YDC. GP I b HPA-3 bb genotype might be a risk factor for AR and recurrent cerebral infarction.</p>

Role of mitochondrial permeability transition pore of hippocampai neurons in process of hydrogen-rich saline attenuating global cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the role of mitochondrial permeability transition pore (mPTP) of hippocampal neurons in process of hydrogen-rich saline attenuating global cerebral ischemia-reperfusion (I/R) injury in rats.Methods Seventy-two male Sprague Dawley rats,weighing 250-300 g,were randomly divided into six groups ( n =12 each):sham operation group (group S),cerebral ischemia-reperfusion group (group IR),normal saline group (group NS),hydrogen-rich saline group (group H),atractyloside group (group A) and hydrogen-rich saline + atractyloside group (group HA).Global cerebral I/R injury was produced by four-vessel occlusion method.Bilateral vertebral arteries were cauterized.Then bilateral common carotid arteries were occluded for 15min and followed by reperfusion.In groups H and HA,hydrogen-rich saline 5 ml/kg was injected intraperitoneally immediately after reperfusion,while equal volume of normal saline was injected in the other four groups.The rats in groups A and HA received intracerebroventricular injection of atractyloside 15 μl 10 min before reperfusion,while groups NS and H received intracerebroventricular injection of equal volume of normal saline.After the neurological behavior was evaluated at 24 h of reperfusion,8 rats in each group were sacrificed and the hippocampi were immediately isolated and homogenized followed by density gradient centrifugation.The opening degree of mPTP was assayed with spectrophotometry and the mitochondrial membrane potential (MMP) was detected with Rhodamine 123 method.Four rats in each group were killed at 72 h of reperfusion and the brains were removed for microscopic examination of the area CA1 of the hippocampus and determination of the number of normal pyramidal neurons.Results Compared with group S,the neurological behavior was compromised,MMP was decreased and mPTP opening degree was enhanced in the other five groups ( P ＜ 0.05).The neurological behavior was better,MMP was increased and mPTP opening degree was decreased in groups H and HA as compared with group IR ( P ＜ 0.05).Compared with group H,the neurological behavior was compromised,MMP was decreased and mPTP opening degree was enhanced in group HA ( P ＜ 0.05).Compared with group IR,the number of normal pyramidal neurons at 72 h of reperfusion in the CA1 region of the hippocampus was higher in group HA ( P ＜0.05).The injury of the CA1 region of the hippocampus at 72 h of reperfusion was attenuated in group H as compared with groups IR,NS,A and HA.Conclusion Hydrogen-rich saline can attenuate global cerebral I/R injury throngh inhibiting the mPTP opening and reducing the dissipation of MMP,thus maintaining the mitochondrial function.

Effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion neurons in mice with oxaliplatin-induced neuropathic pain / 中华麻醉学杂志

Objective To investigate the effects of gabapentin on high-voltage-activated calcium currents in dorsal root ganglion (DRG) neurons in mice with oxaliplatin-induced neuropathic pain (NP). Methods Pathogen-free male Kunming mice aged 6 weeks weighing 20-25 g were used in this study. NP was induced by injection of intraperitoneal oxaliplatin 3 mg/kg. Successful induction of NP was defined as the mechanical paw withdrawal threshold (MWT) measured at 3 d after oxaliplatin administration decreased to 40% of the baseline ( before administration of oxaliplatin). Forty-one mice in which NP was successfully induced were randomly divided into 2 groups: NP group ( n = 20) and gabapentin group (group G, n = 21 ). Another 10 normal mice served as control group (group C). At 3 days after oxaliplatin administration, gabapentin 100 mg/kg was injected intraperitoneally once a day for 3 consecutive days in group G, while C and NP groups received the equal volume of normal saline.MWT to von Fray filament stimulation was measured immediately before and 1-3 days after gabapentin administration (T1-4). After the last measurement of MWT, bilateral L4.5 DRG was collected and neurons were isolated. The high-voltage-activated calcium currents were recorded using whole-cell patch-clamp technique. The peak current density and the voltage where half of the current was activated ( Va1/2 ) or inactivated ( Vi 1/2 ) were calculated. Results Compared with group C, MWT at T1-4 was decreased, the peak current density and Vi1/2 were significantly increased in group NP, and MWT at T1 was decreased in group G ( P ＜ 0.05). There was no significant difference in the peak current density, Vi1/2 and Va1/2 between C and G groups ( P ＞ 0.05). MWT at T2-4 was significantly increased, while the peak current density and Vi1/2 were significantly decreased in group G compared with group NP (P ＜ 0.05). Conclusion Gabapentin can reduce oxaliplatin-induced NP in mice through inhibiting high-voltage-activated calcium currents and promoting the inactivation of the channels in DRG neurons.

Effects of hydrogen-rich saline combined with mild hypothermia on cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To investigate the effect of hydrogen-rich saline combined with mild hypothermia on cerebral ischemia-reperfusion (IR) injury in rats. Methods Fifty male SD rats, aged 9-10 weeks, weiging 250-300 g, were randomly divided into 5 groups (n= 10 each): sham operation group (group S), group IR, hygrogen-rich saline group (group H), mild hypothermia group (group M) and hydrogen-rich saline + mild hypothermia group (group HM). In group IR, H, M and HM cerebral IR was induced by 15 min ligation of bilateral carotid artery followed by 6 h reperfusion. In group H and HM intraperitoneal hydrogen-rich saline 5 ml/kg was injected immediately after reperfusion, while the equal volume of normal saline was injected instead of hydrogen-rich saline in the other three groups. At the same time, the rectal temperature was maintained at 37-38 ℃ in group S,IR and M, while it was reduced to 32-34 ℃ by physical method within 15 min, lasting for 6 h, in group M and HM. The animals were sacrificed after 6 h of reperfusion, and then the hippocampus was removed for microscopic examination. The expression of HO-1 and content of MDA and TNF-α were determined by Western blot. Results The cerebral IR injury was attenuated in group H, M and HM compared with group IR, with the slightest injury in group HM. The expression of HO-1 and content of MDA and TNF-α were significantly higher in group IR, H, M and HM than in group S. The expression of HO-1 was significantly higher, while the content of MDA and TNF-α were lower in group H, M and HM than in group IR, and in group HM than in group H and M. There was no significant difference in the expression of HO-1 and content of MDA and TNF-α between group H and M. Conclusion Hydrogen-rich saline combined with mild hypothermia can attenuate cerebral I/R injury in rats via up-regulating the expression of HO-1 and decreasing the content of MDA and TNF-α in hippocampus.

Novel quantitative method for evaluating oxygen/glucose deprivation-induced injury of hippocampal slices / 浙江大学学报·医学版

OBJECTIVE: To establish a simple, sensitive in vitro method to evaluate oxygen/glucose deprivation (OGD)-induced injury of brain hippocampal slices in rats. METHODS: Rat hippocampal slices were incubated in 2% 2, 3, 5-triphenyltetrazolium chloride (TTC) solution after oxygen/glucose deprivation. They were then soaked in a measured volume of ethanol and dimethylsulfoxide (50:50) to extract the TTC formazan Product which was then measured by spectrophotometry. OGD induced LDH release was simultaneously measured. RESULTS: Progressive prolongation of OGD induced hippocampal injury resulted in decreased formazan coloration as determined by spectrophotometry. There was a parallel increase in LDH release, thus a negative correlation in these two products was noted. (r=-0.933,P <0.01). The injury was attenuated in the brain slices pre-treated with nimodipine, dexamethasone, and ketamine, but not ONO-1078. CONCLUSION: Solvent extraction and spectrophotometric quantification of formazan represents an objective measurement of OGD-induced injury of rat hippocampal slices.