Experimental And Clinical Study On Transient Ischemic Attack

PartⅠExperimental study on transient ischemic attackSection 1 Effects of platelet activation and tirofiban on oxidative stress-induced transient cerebral ischemia-like attack in miceObjective To explore the mechanism of transient cerebral ischemia-like attack(TIA-like attack) induced by oxidative stress in Kunming mice.Methods Mice model of TIA-like attack were established by intravenous injection of tert-butyl hydroperoxide (t-BHP, 0.11mol/L,0.75ml/kg) and hypoxia (the animal was put into a closed container 0.3L for 10 min). Tirofiban (0.25mg/kg) was given through vena caudalis before injection of t-BHP and hypoxia. Ninety-five Kunming mice were divided into 5 groups , including model group, tirofiban group and their corresponding groups for measurement of soluble P-selectin in serum before TIA-like attack (n = 20), control group (n = 15). The onset time of symptom,symptom score and serum P-selectin levels were determined in each group.Results Serum soluble level of P-selectin in the model group was significant higher than that in the control group before TIA-like attack [(4.17±0.18) vs (0.82±0.07)ng/ml, P<0.05], but there was no significant difference between the model group and the tirofiban group. The average time of symtom onset in the tirofiban group was later than that in the model group [(4.70±0.92) vs(3.75±1.12)days, P<0.05]. Symptom score was also lower on the fourth and fifth day in the tirofiban group than that in the model group(P<0.05).Conclusions Platelet activation and microthrombus were induced by oxidative stress in the mice model of TIA-like attack. Inflammatory response after platelet activation might also contribute to this model.Section 2 Effects Of endothelial dysfunction and ginkgo biloba extractin on xidative stress-induced transient cerebral ischemia-like attack in miceObjective To investigate the effects of vascular endothelial dysfunction on TIA-like attack induced by oxidative stress in Kunming mice.Methods: Mice model of TIA-like attack was established by intravenous injection of t-BHP(0.11mol/L,0.75ml/kg) and hypoxia (the animal was put into a closed container 0.3L for 10 min). Ginkgo biloba extract (EGb761) was given by intraperitoneal injection before injection of t-BHP and hypoxia. Ninety-three Kunming mice were divided into 7 groups, including model group, 10mg/kg and 20mg/kg EGb761 groups (n = 15), their corresponding groups for measurement of NOS (nitricoxide synthase), NO (nitric oxide), ET-1 (endothelin-1) in blood before TIA-like attack and control group (n = 12). The onset time of symptom,symptom score and blood levels of NO, ET-1 and NOS activity (before TIA-like attack) were determined in each group.Results Before TIA-like attack, the serum total NOS activity[(22.27±2.31)vs(27.17±3.27)U/ml, P<0.05] and NO level [(29.61±3.08)vs(43.43±4.24)umol/L, P<0.05]were significant lower in the model group than that in the control group, whereas the plasma level of ET-1 [(85.88±2.58)vs(50.07±4.40)ng/ml , P<0.05] was significant higher in the model group than that in the control group. There was no significant difference in serum iNOS (inducible nitric oxide synthase) activity between the model and the control group. EGb761 caused dose-dependent effects on mice model of TIA-like attack, such as increasing the serum level of NO and total NOS activity, decreasing the plasma level of ET-1, reducing the incidence of mice model, lowering the symptom score, delaying the time of symptom onset (P<0.05).Conclusions Vascular endothelial dysfunction and cerebral vasospasm induced by oxidative stress played an important role in the mice model of TIA-like attack.PartⅡClinical study on transient ischemic attackSection 1 Diffusion-Weighted MRI abnormolities and Clinical characteristics in patients with transient ischemic attackObjective We assessed the correlation between clinical characteristics and diffusion-weighted MRI (DWI) abnormalities in patients with transient ischemic attack (TIA) to further evaluate the usefulness of new definition of TIA.Methods A prospective analysis was performed on all TIA patients who had undergone a MRI scan after symptom onset and entered in the hospital during April 2006～September 2007. The relationship between patients'clinical presentation and DWI abnormalities was then analyzed. Results DWI-detected abnormalities were present in 40 of 84 cases (47.6%). Nineteen of the 22 patients with symptoms lasting equal or more than 1 hour had DWI lesions. Patients with positive DWI scans were more likely to have had symptom duration≥1 hour, aphasia and motor deficits than patients with negative DWI scans. Intracranial large-artery disease and vulnerable plaque were more common in patients with DWI abnormalities. In 31 of 40 cases, a DWI abnormality was present on both DWI and conventional imaging except that 7 patients were identified retrospectively.Conclusions TIA patients with symptom duration≥1 hour are more likely to have TIA-related infarcts. Intracranial large-artery disease and vulnerable plaque are the main cause of DWI abnormalities in patients with TIA. The new definition of TIA is not only useful for rapid evaluation and treatment of patients with TIA, but also helpful in diagnosising TIA accurately. On the other hand, its generalization is limited by the reliance on imaging techniques.Section 2 Short-term prognosis of TIA patients with diffusion-weighted MRI abnormalitiesObjective To investigate the relationship between the results of diffusion-weighted imaging and short-term prognosis of patients with TIA.Methods Clinical data, diffusion-weighted MRI (DWI) and magnetic resonance angiography (MRA) findings were collected in a cohort of hospitalized TIA patients from April 2006 to September 2007. The ABCD score was applied to all patients. Then the relationship between the results of DWI and stroke occurred during the 90-day follow-up was analyzed.Results A total of 35 (30.7%) patients had cerebral infarction within 90 days after symptoms onset, while 24(21.1%)patients occurred within 7 days. By multiple logistic regression analysis, ABCD score (odds ratio[OR],2.75; 95% confidence interval [CI],1.35～5.59; P<0.05) was an independent predictor of 7-day risk of stroke. At the same time , ABCD score (OR,3.19; 95%CI,1.47～6.92; P<0.05), DWI abnormalities (OR,9.37;95%CI,1.42～61.66;P < 0.05), and extracranial large-artery disease (OR,7.92;95%CI,1.22～51.44; P<0.05) were each independently associated with 90-day risk of stroke.Conclusions TIA patients with DWI abnormalities indicate an increased risk for future stroke. The ABCD score and extracranial large-artery disease were also helpful in detecting TIA patients at higher risk of stroke during the 90-day follow-up.Section 3 A comparative study on clinical characteristics of transient ischemic attack with diffusion-weighted MRI abnormalities and ischemic strokeObjective To establish similarities and differences among TIA with DWI abnormalities(transient symptoms associated with infarction,TSI),TIA without DWI abnormalities, and ischemic stroke (IS).Methods Demographic, Clinical, and in-hospital outcome data were collected in 84 consecutive TIA patients and a contemporaneous group of 45 completed stroke patients. All underwent diffusion-weighted imaging (DWI) and magnetic resonance angiography (MRA) on admission. Intracranial artery disease and infarct volume were determined in each group. Then the clinical and imaging features among them were analyzed.Results TIA-related infarcts were smaller than those associated with IS (mean, 1.63 vs 10.34 cm3; P<0.05), but a substantial overlap in infarct size was exist between the two groups. Intracranial large-arterial occlusive disease was more common in IS patients. There were 2 recurrent TIAs and 11 strokes (27.5%) among patients with TSI; 4 recurrent TIAs and 1 strokes (2.3%) among TIA patients without DWI abnormalities; and 1 recurrent stroke (2.2%) and no TIAs among IS patients. Patients with TSI were at significantly higher risk of in-hospital recurrent stroke (P<0.05).Conclusions TSI may be a separate clinical entity with unique features separate from TIA without DWI abnormalities and IS.