Writing Committee of Korean clinical practice guidelines for secondary prevention of stroke has reviewed recent randomized controlled trials of cilostazol published after the first edition of Korean clinical practice guidelines that considered evidences published before June 2007. Two clinical trials and 1 meta-analysis which compared cilostazol directly with aspirin in the prevention of stroke in patients with cerebral infarction or transient ischemic attack (TIA) were identified and included for the current guideline update. Review of findings indicates that cilostazol as compared to aspirin achieved a greater reduction of stroke as well as composite vascular events of stroke, myocardial infarction, and vascular death. For safety, cilostazol was associated with fewer major bleeding events than aspirin. Accordingly, new recommendations for cilostazol are made for prevention of stroke in the setting of noncardioembolic stroke or TIA. Changes in the guidelines necessitated by new evidences will be continuously reflected in future guidelines.
Aspirin ; Cerebral Infarction ; Hemorrhage ; Humans ; Ischemic Attack, Transient ; Myocardial Infarction ; Secondary Prevention ; Stroke ; Tetrazoles ; Writing

OBJECTIVE: The key point of anesthesia management in carotid endarterectomy (CEA) is to maintain adequate cerebral perfusion during carotid artery occlusion. Placement of shunt is one of the common surgical methods. This study analyzed the effects of different shunt strategies on cerebral infarction after carotid endarterectomy. METHODS: A total of 443 patients who underwent CEA under general anesthesia within 2 years were divided into imaging group (based on preoperative imaging data as the basis for shunt) and stump pressure group (based on intraoperative stump pressure as the basis for shunt). The preoperative demographic data, past medical history, degree of cervical vascular stenosis, blood pressure at each time point during the perioperative period, vascular blocking time, whether to place the shunt, postoperative hospital stay, cerebral infarction during hospitalization, and other adverse events were collected and compared between the two groups. On this basis, the preoperative and intraoperative conditions with significant differences were matched with propensity scores, and the influence of different shunt strategies on postoperative cerebral infarction was analyzed. RESULTS: In the study, 268 patients in the imaging group and 175 patients in the stump pressure group underwent CEA under general anesthesia. There were statistically significant differences in basic conditions and blood pressure at each time point between the two groups. After matching the propensity scores, 105 patients in each of the two groups were matched. The basic conditions of the patients before surgery and the difference in blood pressure of the two groups at each time point were not statistically significant. There was no significant diffe-rence in the incidence of postoperative cerebral infarction between the two groups (1.9% vs. 1.0%, P>0.999). The intraoperative shunt rate in the imaging group was lower than that in the stump pressure group (0 vs. 22.9%, P < 0.001). The postoperative hospital stay in the imaging group was 8 (7, 8) days, which was longer than the stump pressure group 5 (4, 6) days (P < 0.001). CONCLUSION The rate of the shunt was lower according to preoperative imaging examination than that according to the residual pressure in our hospital. There is no significant difference in the incidence of cerebral infarction during the postoperative hospital stay. The effect of different shunt strategies on cerebral infarction needs further study.
Anesthesia, General ; Blood Pressure ; Cerebral Infarction/prevention & control* ; Endarterectomy, Carotid/adverse effects* ; Humans ; Prostheses and Implants

BACKGROUND AND PURPOSE: Treatment with atorvastatin (80 mg) in stroke secondary prevention for patients with prior intracranial hemorrhage (ICH) has been associated with a higher frequency of ICH. The aim of this study was to determine whether 20 mg/day atorvastatin is linked to stroke recurrence in Chinese ischemic stroke patients with prior ICH. METHODS: A single-center retrospective cohort study was conducted, involving 354 cases from 395 Chinese in-patients who had ischemic stroke with prior ICH history in Beijing Chaoyang hospital from May 1, 2005 to October 31, 2010. Survivors were followed by telephone interviews for 12-60 months. Cox regression and Kaplan-Meier plot analysis were used to evaluate the effect of 20 mg/day atorvastatin on cerebral infarction and ICH recurrence. RESULTS: The overall rate of stroke recurrence was lower in the 20 mg/day atorvastatin group (chi2=6.687, p=0.022) than in the control group. The incidence of cerebral hemorrhage was increased by 20 mg/day atorvastatin for ischemic stroke cases with a history of ICH compared to those not receiving the drug, but the difference was not significant [hazard ratio (HR)=1.097, 95% confidence interval (CI)=0.800-1.243, p=0.980]. The incidence of ischemic stroke recurrence was significantly reduced in subjects receiving atorvastatin (HR=0.723, 95% CI=0.578-0.862, p=0.028), and the mean duration of all stroke recurrences was significantly prolonged, compared with those not exposed to the drug (chi2=5.351, p=0.021). The mean duration of ICH recurrence appeared to have shortened with atorvastatin, but the difference was not significant (chi2=0.680, p=0.480), and the mean duration of cerebral infarction recurrence was significantly prolonged (chi2=8.312, p=0.004). CONCLUSIONS: Medication with 20 mg/day atorvastatin may be beneficial in reducing ischemic stroke recurrence in ischemic stroke patients with a history of ICH and is not associated with an increased risk of ICH recurrence.
Atorvastatin Calcium ; Asian Continental Ancestry Group ; Cerebral Hemorrhage ; Cerebral Infarction ; Cohort Studies ; Heptanoic Acids ; Humans ; Incidence ; Interviews as Topic ; Intracranial Hemorrhages ; Pyrroles ; Recurrence ; Retrospective Studies ; Secondary Prevention ; Stroke ; Survivors

BACKGROUNDA recent study demonstrated that the inflammatory response accompanying necrotic brain injury played an important role in stroke. Thus, inhibition of this response may help to stop the expansion of infarcts. It has been also shown that the spleen, a major peripheral immune organ, plays a role in stroke-induced immune responses. This study aimed to establish rat models of middle cerebral artery occlusion (MCAO) and to investigate the effect of splenectomy and possible mechanisms in that rat models.

METHODSInfarct size in a stroke model was measured with the Nissl body staining method, numbers of inflammatory cells in ischemic regions were detected by immunofluorescence staining, and inflammatory factors were assayed by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR) in brain homogenates and sera. The significance of differences was determined by one-way analysis of variance (ANOVA) followed by the least significant difference post hoc test.

RESULTSInfarct size in the brain of rats that underwent splenectomies 2 weeks before permanent MCAO ((34.93 ± 3.23)%) was over 50% smaller than that of rats subjected to the stroke surgery alone ((74.33 ± 2.36)%, P < 0.001; (77.30 ± 2.62)%, P < 0.001). Lower numbers of T cells, neutrophils, and macrophages in brain tissue and lower levels of pro-inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, were observed in rats that underwent splenectomies, compared with the two other groups, but splenectomized rats showed higher levels of the anti-inflammatory factor IL-10 in the brain.

CONCLUSIONThe mechanism(s) by which splenectomy protects brain from damage induced by stroke may correlate with the decreased numbers of inflammatory cells and changes in inflammatory cytokines.

Animals ; Cerebral Infarction ; prevention & control ; Cytokines ; secretion ; Inflammation ; prevention & control ; Male ; Rats ; Rats, Sprague-Dawley ; Splenectomy ; Stroke ; complications ; T-Lymphocytes ; immunology

Adult ; Cerebral Infarction ; etiology ; prevention & control ; Female ; Humans ; Immunosuppressive Agents ; adverse effects ; Intracranial Hemorrhages ; etiology ; prevention & control ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Tacrolimus ; adverse effects

OBJECTIVETo test whether folic acid offers protection of the brain tissue against acute cerebral infarction in rats.

METHODSSprague-Dawley rats were divided into control (n=8), pre-treatment (n=12) and treatment (n=16) groups, all having routine feed for 7 days. The rats in the control and treatment groups were given normal saline daily, and those in the pre-treatment group received folic acid suspension daily. All the rats were then subject to middle cerebral artery occlusion (MCAO) for 24 h followed by reperfusion. On and after the operation day, the rats in the control group were given normal saline and those in the other two groups were given folic acid suspension daily. Neural function deficiency was evaluated on a daily basis after the operation, and on day 6 after the operation, brain biopsy was performed for examination with TTC staining. Monocyte chemokine -1 (MCP-1) in both normal and infarct tissues was measured by ELISA.

RESULTSOn day 6 after the operation, the neural function deficiency scores of the control, pre-treatment and treatment groups were 4.56∓3.63, 2.94∓2.94 and 1.00∓1.00, and the percentages of the infarct area (to the whole brain area) were (44.23∓10.06)%, (20.64∓6.78)% and (14.61∓13.51)%, respectively. The contents of MCP-1 in the infarct area of the brain tissues were 168.58∓107.21 ng/L, 152.91∓64.78 ng/L, and 97.74∓46.19 ng/L in the 3 groups, respectively.

CONCLUSIONFolic acid can protect brain tissue against acute cerebral infarction in rats.

Animals ; Cerebral Infarction ; drug therapy ; Female ; Folic Acid ; therapeutic use ; Infarction, Middle Cerebral Artery ; drug therapy ; Neuroprotective Agents ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Thrombolytic Therapy

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

OBJECTIVE: To explore the impact on cerebral protection of Trichostatin A (TSA) preconditioning in rats with middle cerebral artery occlusion (MCAO); the relationship between cerebral protection of TSA and interleukin-1 beta (IL-1β); and the impact of age on the mechanism of cerebral protection of TSA. METHODS: The modified suture method was used to create stable a MCAO model. A total of 96 male SD rats were assigned randomly to four groups: a control group, a dimethyl sulfoxide (DMSO) preconditioned group, a low-dose (0.03 mg/kg) TSA-preconditioned group, and a high-dose (0.1 mg/kg) TSA-preconditioned group. Each group included four sub-groups for reperfusion for 6, 12, 24 and 48 hours, respectively, 6 rats per sub-group. An additional, eighteen healthy, male Sprague Dawley (SD) rats that received TSA preconditioning (0.1 mg/kg) were divided into three groups based on their age: young, mid-age, and old, One-way analysis of variance was used to compare the differences between groups, and the Spearman rank correlation was used to examine relationships between IL-1β concentrations in blood and cerebrospinal fluid and cerebral infarction volume. RESULTS: The cerebral infarction volume of rats in the high-dose TSA group was less than that of the other 3 groups (P<0.05). The IL-1β in blood and the cerebrospinal fluid of rats in the highdose TSA group was lower than that in control and DMSO groups (P<0.05); for the low-dose TSA group IL-1β levels were statistically the same as in controls. The Spearman rank coefficients were 0.841 and 0.618 for cerebral infarction volume correlate to blood IL-1β and to cerebrospinal fluid IL-1β, respectively (P<0.05). No statistical differences were found in cerebral infarction volume and IL-1β levels in blood or cerebrospinal fluid (P>0.05). CONCLUSION High-dose TSA preconditioning reduces cerebral infarction volume and decreases IL- 1β levels in blood and cerebrospinal fluid; age does not affect these parameters.
Animals ; Histone Deacetylase Inhibitors ; therapeutic use ; Hydroxamic Acids ; therapeutic use ; Infarction, Middle Cerebral Artery ; physiopathology ; Interleukin-1beta ; metabolism ; Ischemic Preconditioning ; methods ; Male ; Rats ; Reperfusion Injury ; prevention & control

BACKGROUND: Cilostazol leads to inhibition of platelet aggregation and to vasodilatation. It is widely used for the secondary prevention of cerebral infarction. However, headache is a well-known adverse effect of cilostazol, and these headaches may be caused by the vasodilation of the cerebral artery. The goal of our study was to assess the frequency and severity of headaches following cilostazol treatment and to evaluate factors related to the development of these headaches. METHODS: Seventy patients with cerebral infarction were included in this study. We measured the carotid intima media thickness (IMT), the distensibility of the carotid artery (CAD), the brachial ankle index (ABI), and the brachial ankle pulse wave velocity (PWV) in order to quantify the degree of atherosclerosis and arterial stiffness. Patients were then given 100 mg of cilostazol in tablet form twice daily. For three days, we evaluated headache incidence and severity using a verbal rating scale (0-10). RESULTS: Twenty three (32.9%) patients reported headache during cilostazol medication and 7 patients had severe headache. Women were more likely to develop headaches than men (p=0.03). In addition, the mean IMT was lower in subjects with cilostazol-induced headache than in the headache-free subjects (0.8+/-0.1 vs 1.01+/-0.2 mm, p=0.001), while CAD was higher in these subjects (0.3+/-0.1 vs 0.25+/-0.1, p=0.03). There was no difference in PWV and ABI. CONCLUSIONS: Lower carotid IMT, increased CAD, and female gender may be associated with the development of cilostazol-induced headache in patients with cerebral inafarction, but not the systemic arterial stiffness.
Animals ; Ankle ; Atherosclerosis ; Carotid Arteries ; Carotid Intima-Media Thickness ; Cerebral Arteries ; Cerebral Infarction ; Female ; Headache ; Humans ; Incidence ; Male ; Platelet Aggregation ; Pulse Wave Analysis ; Secondary Prevention ; Tetrazoles ; Vascular Stiffness ; Vasodilation