Acute Stage Of Stroke Research Articles

Effects of Dehydration on Brain Perfusion and Infarct Core After Acute Middle Cerebral Artery Occlusion in Rats: Evidence From High-Field Magnetic Resonance Imaging.

Background: Dehydration is common among ischemic stroke patients and is associated with early neurological deterioration and poor outcome. This study aimed to test the hypothesis that dehydration status is associated with decreased cerebral perfusion and aggravation of ischemic brain injury.Methods: Diffusion-weighted imaging and arterial spin labeling perfusion MR imaging were performed on rats with middle cerebral artery occlusion (MCAO) by using a 9.4T MR imaging scanner to measure the volume of infarction and relative cerebral blood flow (rCBF) after infarction. Twenty-five rats were assigned to either a dehydration group or normal hydration group, and dehydration status was achieved by water deprivation for 48 h prior to MCAO.Results: The volume of the infarction was significantly larger for the dehydration group at the 4th h after MCAO (p = 0.040). The progression in the infarct volume between the 1st and 4th h was also larger in the dehydration group (p = 0.021). The average rCBF values of the contralateral normal hemispheres at the 1st and the 4th h were significantly lower in the dehydration group (p = 0.027 and 0.040, respectively).Conclusions: Our findings suggested that dehydration status is associated with the progression of infarct volume and decreases in cerebral blood flow during the acute stage of ischemic stroke. This preliminary study provided an imaging clue that more intensive hydration therapies and reperfusion strategies are necessary for the management of acute ischemic stroke patients with dehydration status.

Antihypertensive therapy in acute ischemic stroke: where do we stand?

Despite the proven benefits of strict blood pressure (BP) control on primary and secondary prevention of stroke, management of acute hypertensive response in the early post-stroke period is surrounded by substantial controversy. Observational studies showed that raised BP on ischemic stroke onset is prognostically associated with excess risk for early adverse events and mortality. By contrast, randomized controlled trials and recent meta-analyses showed that although antihypertensive therapy effectively controls elevated BP in the acute stage of ischemic stroke, this BP-lowering effect is not translated into improvement in the risk of death or dependency. On this basis, acute and aggressive BP responses within 24 h of stroke onset should be avoided and antihypertensive therapy is recommended only for patients presenting with acute ischemic stroke and BP > 220/120 mmHg or those with BP > 185/110 mmHg who are eligible for therapy with intravenous tissue plasminogen activator. By contrast, recent clinical trials showed that intensive BP lowering to levels < 140 mmHg for systolic BP is safe and lowers the risk of hematoma expansion in patients with acute intra-cerebral hemorrhage and this BP target is recommended by current international guidelines. Herein, we provide an overview of randomized trials and recent meta-analyses on the management of hypertension during the acute stage of ischemic stroke. We discuss several areas of uncertainty and conclude with perspectives for future research.

Using Smartphones to Collect Quantitative Data on Lower Limb Functionality in People Who Have Suffered a Stroke

GoalThe main objective was to use the inertial sensor integrated into a smartphone to collect quantitative data on lower limb functioning during execution of the timed up and go test and sit to stand test by people in the acute stage of stroke. The secondary objective was to analyze whether smartphones provide reliable quantitative data on performance of these functional tests. Material and MethodsCross-sectional analytical study involving 8 elderly people (M age = 67.50 years). Both tests were performed to parametrize and analyze the functionality, balance, and strength of lower limbs using an inbuilt inertial sensor of the smartphone. Time, difference in trunk position, angular displacement, angular velocity, and angular acceleration were measured and calculated for each stage at which both functional tests were divided. ResultsThe obtained results highlight the similarity in the angular displacement during the 2 stages into which the sitting-standing (flexion: 38.85° and extension: 38.10°) and the standing-sitting (flexion: 36.42° and extension: 36.45°) phases were divided. Mean velocities of .59 m/s and .61 m/s were registered during outward and return walking phases. The intra- and interobserver reliability of variables recorded with the inbuilt inertial sensor ranged from .860 to .897. ConclusionsBalance and muscle strength problems of stroke patients gave rise to the use of compensatory mechanisms when getting up from or sitting down in a chair and resulted in a reduction in walking speed that is sufficient to make walking in community contexts difficult. Smartphones has excellent reliability when used to quantify lower limb functioning in stroke patients.

Abnormal Metabolic Connectivity in Rats at the Acute Stage of Ischemic Stroke.

Stroke at the acute stage is a major cause of disability in adults, and is associated with dysfunction of brain networks. However, the mechanisms underlying changes in brain connectivity in stroke are far from fully elucidated. In the present study, we investigated brain metabolism and metabolic connectivity in a rat ischemic stroke model of middle cerebral artery occlusion (MCAO) at the acute stage using 18F-fluorodeoxyglucose positron emission tomography. Voxel-wise analysis showed decreased metabolism mainly in the ipsilesional hemisphere, and increased metabolism mainly in the contralesional cerebellum. We used further metabolic connectivity analysis to explore the brain metabolic network in MCAO. Compared to sham controls, rats with MCAO showed most significantly reduced nodal and local efficiency in the ipsilesional striatum. In addition, the MCAO group showed decreased metabolic central connection of the ipsilesional striatum with the ipsilesional cerebellum, ipsilesional hippocampus, and bilateral hypothalamus. Taken together, the present study demonstrated abnormal metabolic connectivity in rats at the acute stage of ischemic stroke, which might provide insight into clinical research.

COGNITIVE IMPAIRMENT, THEIR DYNAMICS AND STRUCTURE IN THE ACUTE AND RECOVERY PERIODS OF STROKE, DEPENDING ON ARTERIAL HYPERTENSION SEVERITY AND DURATION

Relevance. Cognitive impairment is common in the post-stroke period. Different characteristics of arterial hypertension (AH), namely its severity, duration and variability of blood pressure, can affect the development of cognitive impairment in stroke patients.&#x0D; Objective: to investigate cognitive impairment, their dynamics and structure in acute and recovering stroke periods, depending on the arterial hypertension severity and duration.&#x0D; Materials and methods. 150 patients with a primary ischemic stroke and history of hypertension: 74 (49,3 %) women and 76 (50,7 %) men, the mean age (67,4±0,7) years have been examined. Neurological deficits was evaluated by the NIHSS scale. The cognitive status was evaluated by the MMSE scale at the end of an acute period of 21 days and 1 year. Diagnosis of hypertension was based on the clinical and instrumental examination results and medical documents. Daily blood pressure monitoring was using on admission and every 4 hours during 6 days of acute stroke stage. Mean SBP, mean DBP, maximum SBP and DBP, standard deviation (SD) of SBP and DBP were studied.&#x0D; Results. By the mean score on the MMSE scale, there are differences in patients during acute post-stroke period, depending on the severity of hypertension: 27,2±0,6 points in the case of hypertension stage 1, 24,3±0,6 in the case of hypertension stage 2 and 20,7±0,8 in case of AH stage 3, (p=0.001). By this indicator, patients with different AH duration were different: 26,4±0,9 points; 25,1±0,5 points; 20,5±0,7 points, respectively. The significance of these differences by the mean values of MMSE score was obtained in patients with a duration of AH less than 5 years and more than 10 years, as well as when comparing the group of "6-10 years" and "over 10 years" (p=0,001).&#x0D; Significant differences in the structure of cognitive deficits severity, depending on the hypertension stage and its duration, were observed only in patients with moderate and severe stroke (p=0,006).&#x0D; Cognitive deterioration a year after a stroke was observed in 40 (31,5 %) patients. They have significantly higher mean values SD 1-3, SD 1-6, SBP on the first day after a stroke, and duration of hypertension.&#x0D; Conclusions. The relationship between the degree of intellectual decline and the duration of hypertension (r=0,592, p=0,001), severity of hypertension (r=0,459, p=0,001) was found. The severity of the neurological deficiency affects the structure of cognitive impairment at discharge in patients with different severity and duration of hypertension, and higher mean values of the variability of blood pressure from 1 to 6 days, SBP on the first day after stroke and higher duration of hypertension in the history is associated with a negative dynamics of cognitive impairment in stroke patients in a year after stroke.

Clinical Significance of Acute and Serial Platelet Function Testing in Acute Ischemic Stroke.

BackgroundWe sought to investigate the clinical implications of platelet reactivity to aspirin and the variability in the platelet reactivity to aspirin during acute periods for the risk of vascular events in patients with acute ischemic stroke.Methods and ResultsThis was a single‐center, prospective, observational study. The aspirin reaction unit was blindly measured at the following two times: after 3 hours of aspirin loading and on the fifth day of aspirin administration. High on‐aspirin platelet reactivity (HAPR) was defined as an aspirin reaction unit ≥550 IU. The primary outcome measure was the 1‐year composite of stroke, myocardial infarction, and vascular death. A total of 805 patients (aged 66±12 years, 61% male) were analyzed in this study. Ninety‐nine of 805 (12.3%) patients and 78 of 558 (14.0%) patients had HAPR at the time of the fifth day of aspirin administration and after 3 hours of aspirin loading measurements, respectively. Patients with HAPR than normal on‐aspirin platelet reactivity at the fifth day of aspirin administration measurement were more likely to have experienced 1‐year vascular event. HAPR at the fifth day of aspirin administration measurement was independently associated with a greater risk of experiencing 1‐year vascular event (hazard ratio, 1.84; 95% confidence interval, 1.07–3.19). Moreover, persistently HAPR substantially increased the risk of 1‐year vascular events (hazard ratio, 3.11; 95% confidence interval, 1.23–7.86).ConclusionsThese results suggest that HAPR during the acute stage of ischemic stroke increases the risk of subsequent vascular events and that serial aspirin reaction unit measurements may identify patients with acute ischemic stroke who are at a higher risk for vascular events. Additional studies are warranted to determine the appropriate treatments for patients with acute ischemic stroke with HAPR.

Plasma Unesterified Fatty-Acid Profile Is Dramatically and Acutely Changed under Ischemic Stroke in the Mouse Model.

Although plasma biomarkers would facilitate rapid and accurate diagnosis of ischemic stroke for immediate treatment, no such biomarkers have been developed to date. In the present study, we tested our hypothesis that plasma unesterified fatty acids (FFA) are altered at early stages of acute ischemic stroke. Plasma was collected from mice 2 h after the permanent middle cerebral artery occlusion (pMCAo) onset, as well as from sham operated and control animals. After 2 h, pMCAo significantly changed the plasma FFA profile with the most dramatic 2- to 3-fold relative increase in very long n-3 and n-6 FFA including 20:4n-6, 22:4n-6, 22:5n-6, and 22:6n-3. Changes in the plasma FFA profile are consistent with FFA liberation from brain phospholipid hydrolyzed under ischemic insult. These results identify, for the first time, the plasma FFA profile as a potential biomarker for an early ischemic stroke within the therapeutic window for thrombolytic treatment. Further studies are required to confirm its specificity and sensitivity in clinical settings.

Phosphorylated recombinant HSP27 protects the brain and attenuates blood-brain barrier disruption following stroke in mice receiving intravenous tissue-plasminogen activator.

Loss of integrity of the blood-brain barrier (BBB) in ischemic stroke victims initiates a devastating cascade of events causing brain damage. Maintaining the BBB is important to preserve brain function in ischemic stroke. Unfortunately, recombinant tissue plasminogen activator (tPA), the only effective fibrinolytic treatment at the acute stage of ischemic stroke, also injures the BBB and increases the risk of brain edema and secondary hemorrhagic transformation. Thus, it is important to identify compounds that maintain BBB integrity in the face of ischemic injury in patients with stroke. We previously demonstrated that intravenously injected phosphorylated recombinant heat shock protein 27 (prHSP27) protects the brains of mice with transient middle cerebral artery occlusion (tMCAO), an animal stroke-model. Here, we determined whether prHSP27, in addition to attenuating brain injury, also decreases BBB damage in hyperglycemic tMCAO mice that had received tPA. After induction of hyperglycemia and tMCAO, we examined 4 treatment groups: 1) bovine serum albumin (BSA), 2) prHSP27, 3) tPA, 4) tPA plus prHSP27. We examined the effects of prHSP27 by comparing the BSA and prHSP27 groups and the tPA and tPA plus prHSP27 groups. Twenty-four hours after injection, prHSP27 reduced infarct volume, brain swelling, neurological deficits, the loss of microvessel proteins and endothelial cell walls, and mortality. It also reduced the rates of hemorrhagic transformation, extravasation of endogenous IgG, and MMP-9 activity, signs of BBB damage. Therefore, prHSP27 injection attenuated brain damage and preserved the BBB in tPA-injected, hyperglycemic tMCAO experimental stroke-model mice, in which the BBB is even more severely damaged than in simple tMCAO mice. The attenuation of brain damage and BBB disruption in the presence of tPA suggests the effectiveness of prHSP27 and tPA as a combination therapy. prHSP27 may be a novel therapeutic agent for ischemic stroke patients whose BBBs are injured following tPA injections.

Hirudotherapy in the treatment of cerebrovascular disease: Past and present

The article summarizes and presents data on the historical experience of medical leeches, numbering more than 30 centuries. The paper reviews the historical and empirical basis of hirudotherapy in the clinical practice worldwide. The peculiarities of hirudotherapy in different countries (USA, Europe, Russia) have been studied at the present time. The therapeutic effects of hirudotherapy in clinical practice are due to the well-investigated saliva content of the medical leech, as well as the local and systemic reflex action on the body in response to the bloodsucking and hemorrhage. We analyze pathogenesis mechanisms of hirudotherapy. Hirudotherapy can reduce ischemia, hypoxia and normalize microcirculation. Hirudotherapy is effective in different groups of patients with cerebrovascular diseases. A number of studies confirm the effectiveness of hirudotherapy in the treatment of patients with essential hypertension, chronic impairment of cerebral circulation, acute stage of ischemic stroke, as well as in post-stroke rehabilitation. There is sufficient evidence for the use of hirudotherapy in cases of cerebrovascular disease for complementary method in the complex treatment and for the prevention of acute cerebrovascular events.

Progressive Assessment of Ischemic Injury to White Matter Using Diffusion Tensor Imaging: A Preliminary Study of a Macaque Model of Stroke.

Background:Previous Diffusion Tensor Imaging (DTI) studies have demonstrated the temporal evolution of stroke injury in grey matter and white matter can be characterized by DTI indices. However, it still remains not fully understood how the DTI indices of white matter are altered progressively during the hyperacute (first 6 hours) and acute stage of stroke (≤ 1 week). In the present study, DTI was employed to characterize the temporal evolution of infarction and white matter injury after stroke insult using a macaque model with permanent ischemic occlusion.Methods and materials:Permanent middle cerebral artery (MCA) occlusion was induced in rhesus monkeys (n=4, 10-21 years old). The brain lesion was examined longitudinally with DTI during the hyperacute phase (2-6 hours, n=4), 48 hours (n=4) and 96 hours (n=3) post-occlusion.Results:Cortical infarction was seen in all animals. The Mean Diffusivity (MD) in lesion regions decreased substantially at the first time point (2 hours post stroke) (35%, p <0.05, compared to the contralateral side) and became pseudo-normalized at 96 hours. In contrast, evident FA reduction was seen at 48 hours (39%, p <0.10) post-stroke. MD reduction in white matter bundles of the lesion area was much less than that in the grey matter during the hyper-acute phase but significant change was observed 4 hours (4.2%, p < 0.05) post stroke . Also, MD pseudonormalisation was seen at 96 hours post stroke. There was a significant correlation between the temporal changes of MD in white matter bundles and those in whole lesion areas during the entire study period. Meanwhile, no obvious fractional anisotropy (FA) changes were seen during the hyper-acute phase in either the entire infarct region or white matter bundles. Significant FA alteration was observed in entire lesion areas and injured white matter bundles 48 and 96 hours post stroke. The stroke lesion in grey matter and white matter was validated by pathological findings.Conclusion: The temporal evolution of ischemic injury to the grey matter and white matter from 2 to 96 hours after stroke onset was characterized using a macaque model and DTI. Progressive MD changes in white matter bundles are seen from hyperacute phase to acute phase after permanent MCA occlusion and temporally correlated with the MD changes in entire infarction regions. MD reduction in white matter bundles is mild in comparison with that in the grey matter but significant and progressive, indicating it may be useful to detect early white matter degeneration after stroke.

Effects of glycemic variability and hyperglycemia in acute ischemic stroke on post-stroke cognitive impairments

AimsWe aimed to investigate the effect of glycemic variability in the acute stage of stroke on the development of post-stroke cognitive impairment (PSCI). MethodsPatients who underwent blood glucose tests at least five times within 7 days after acute ischemic stroke were included. Factors related to glycemic variability (standard deviation (SD), coefficient of variance (CV), and mean absolute glucose (MAG)) were calculated; neuropsychological assessments were administered 3 months after stroke. PSCI was defined as a score of less than −2 SDs for age-, sex-, and education-adjusted means in at least one cognitive domain. ResultsA total of 354 patients were enrolled. PSCI was identified in 74 (20.9%) subjects. In the diabetic group (n = 87), MAG was a significant predictor for PSCI (adjusted OR, 1.94; 95% CI, 1.11–3.42); however, it was not significant in the non-diabetic group, although PSCI exhibited an increasing tendency within higher SD and MAG tertiles. Moreover, hyperglycemia demonstrated a detrimental effect on PSCI, regardless of diabetes status; this effect did not appear in poorly-controlled diabetic patients with HbA1c ≥ 8.0%. ConclusionsGlycemic variability and hyperglycemia during acute ischemic stroke were identified as novel predictors for PSCI. Although this result is not evidence of a causal relationship, our study suggests that monitoring glycemic index and controlling its variability during the acute phase of ischemic stroke may help to prevent poor cognitive outcomes.

Korean Red Ginseng Pretreatment Protects Against Long-Term Sensorimotor Deficits After Ischemic Stroke Likely Through Nrf2.

Endogenous neuroprotective mechanisms by which the brain protects itself against noxious stimuli and recovers from ischemic damage are key targets of stroke research, ultimately facilitating functional recovery. Transcriptional factor Nrf2, enriched in astrocytes, is a master regulator of endogenous defense systems against oxidative stress and inflammation. Korean Red Ginseng (Ginseng), one most widely used herbal medicine, has exhibited promising potentials in neuroprotection. Our study aimed to determine whether the standardized Ginseng extract pretreatment could attenuate acute sensorimotor deficits and improve long-term functional recovery after ischemic stroke though Nrf2 pathway and whether reactive astrogliosis is associated with such effect. Adult Nrf2−/− and matched wildtype control (WT) mice were pretreated with Ginseng orally for 7 days prior to permanent distal middle cerebral artery occlusion (pdMCAO). Using an optimized method that can accurately assess either severe or mild pdMCAO-induced sensorimotor deficits, neurobehavioral tests were performed over 28 days. The progression of lesion volume and the evolution of astrocytic and microglial activation were determined in the acute stage of ischemic stroke after pdMCAO (0–3 days). Nrf2-downstream target antioxidant genes expression levels was assessed by Western blot. We found that Ginseng pretreatment ameliorated acute sensorimotor deficits and promoted long-term functional recovery, prevented the acute enlargement of lesion volume (36.37 ± 7.45% on day 3), attenuated reactive astroglial progression but not microglia activation, and enhanced the induction of Nrf2-downstream target proteins after ischemic insult in WT mice, an effect which was lost in Nrf2 knockouts. The spatiotemporal pattern of reactive astrogliosis evaluation correlated well with acute ischemic damage progression in an Nrf2-dependent fashion during the acute phase of ischemia. In contrast, Nrf2 deficiency mice exhibited exacerbated ischemic condition compared to WT controls. Together, Ginseng pretreatment protects against acute sensorimotor deficits and promotes its long-term recovery after pdMCAO, at least partly, through Nrf2 activation, highlighting the potential efficacy of oral consumption of Ginseng for stroke preventative intervention in patients who are at great risk of recurrent stroke or transient ischemic attack. The attenuated reactive astrogliosis contributes to the Nrf2 pathway related neuroprotection against acute ischemic outcome and substantially long-term sensorimotor deficits in the context of ischemic stroke under pdMCAO.

C-Reactive Protein Can Be an Early Predictor of Poststroke Apathy in Acute Ischemic Stroke Patients

Apathy is a multidimensional syndrome referring to a primary lack of motivation that occurs frequently in survivors of stroke. Higher C-reactive protein (CRP) level was associated with higher apathy scores among Alzheimer disease cases. However, data on the relationship between CRP levels and apathy in patients with stroke are lacking. So, we hypothesized an association between CRP and poststroke apathy (PSA). Two hundred ninety-two consecutive patients with stroke were recruited within 7 days after stroke. Apathy symptoms were assessed at baseline and at 1, 3, and 6 months after stoke using the Apathy Evaluation Scale-Clinical (AES-C). Demographic and clinical information were obtained using the National Institutes of Health Stroke Scale (NIHSS) scores, Barthel Index (BI) scores, Mini-Mental State Examination (MMSE) scores, Hamilton Depression Scale (HAMD) scores, and Hamilton Anxiety Scale (HAMA) scores. CRP was measured at baseline. The presence and the location of infarcts were evaluated using magnetic resonance imaging. Apathy at baseline was significantly associated with body mass index (BMI), NIHSS, BI, MMSE, HAMD, and CRP (P < .05) upon admission. PSA at 6 months was significantly associated with elevated CRP concentrations, high AES-C score, and low BI score (P < .05) upon admission. The AES-C scores peaked 3 months after stroke, but then abated over 6 months. CRP, BMI, MMSE, depression, and disability are closely related to apathy during the acute stage of ischemic stroke. Lower BI scores, higher CRP concentrations, and apathy in acute stroke phase increased the risk of PSA at 6 months.

Limb remote ischemic post-conditioning mitigates brain recovery in a mouse model of ischemic stroke by regulating reactive astrocytic plasticity

Maladaptive alterations of astrocytic plasticity may cause brain edema in the acute stage of stroke and glial scar formation in the recovery stage. The present study was designed to investigate the potential regulation of limb remote ischemic post-conditioning (RIPC) on astrocytic plasticity in experimental cerebral ischemia-reperfusion injury. Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 1 h in C57BL/6 mice, who were treated with RIPC immediately after reperfusion. The results showed that RIPC decreased hemispheric swelling, infarct volume and brain atrophy, and increased neurological function recovery and survival rates of ischemic mice at 3 and 14 d after cerebral ischemia-reperfusion, respectively. Moreover, the proportion of astrocyte subtypes was adjusted by RIPC treatment, demonstrated by decreased expression of the fibrous type (glial fibrillary acidic protein, GFAP) and increased expression of the protoplasmic type (glutamine synthetase, GS) in the ipsilateral side of the mouse brain at 14 d after cerebral ischemia-reperfusion. RIPC treatment adjusted the proportion of GFAP subtypes by downregulating the protein level of GFAPα, as well as upregulating the GFAPδ/GFAPα ratio in the ipsilateral side at 3 and 14 d after reperfusion. Notably, RIPC inhibited the phosphorylation of signal transducer and activators of transcriptions 3 (p-STAT3) in the ipsilateral side at 3 and 14 d after cerebral ischemia-reperfusion. Taken together, the results show that RIPC treatment could regulate reactive astrocytic plasticity and inhibition of STAT3 phosphorylation to promote neurological function recovery following ischemic stroke.

Exploring Chinese medicine and Western medicine group modules in acute phase of ischemic stroke disease

Under the theoretical guidance of "combination of disease and syndrome， correspondence between syndrome and prescription， and dynamic space-time"， 11 135 acute ischemic stroke patients were collected from hospital information system(HIS) of many 3A grade hospitals of traditional Chinese medicine. Complex network analysis was adopted to obtain the core syndrome elements in different periods of acute ischemic stroke patients， and it was found that the core syndrome elements were blood stasis syndrome， phlegm， endogenous wind， Yin deficiency， Qi deficiency， heat， hyperactivity of liver Yang， liver， and kidney of patients in hospital for the first day， and during 8-14 d in hospitalization， the core syndrome elements were blood stasis， phlegm， Yin deficiency， Qi deficiency， endogenous wind， hyperactivity of liver Yang， liver， and kidney. The data with "improved" and "cured" treatment outcomes were adopted for complex network analysis and correlation analysis to identify the Chinese and Western medicine group modules in patients with different disease conditions in different phases after hospitalization. It was found that the Chinese and Western medicine modules within 14 d after hospitalization mainly included "blood-activating and stasis-dissolving module "consisted by "anti-platelet drug + circulation-improving medicine(or anticoagulant drug and anti-fibrinogen drug， et al) + blood-activating and stasis-dissolving drugs"， as well as "stasis-dissolving and phlegm-reducing module" consisted by "anti-platelet drugs + circulation-improving medicine(or anticoagulant drug and anti-fibrinogen drug， et al) + phlegm refreshing drug". The core Chinese and Western medicine modules in patients with urgent and general conditions within 7 d after hospitalization mainly used "blood-activating and stasis-dissolving module" and "stasis-dissolving and phlegm-reducing module". Three or more Chinese medicine and Western medicines module with more than 1% utilization rate was not found in the patients with critical disease condition in admission. The urgent， general and critically ill patients in admission mainly used "blood-activating and stasis-dissolving module" in 8-14 d. From the real world medical big data research， it was found that the combined use of Chinese and Western medicines were consistent with "combination of disease and syndrome， correspondence between syndrome and prescription， and dynamic space-time" theory， and multiple multidimensional dynamic Chinese medicine and Western medicine group modules of "patient-syndrome-drug-time-effective" at the acute ischemic stroke stage were dug out， forming the method of Chinese and Western medicine combination research based on electrical medical big data.

Abstract TP368: Effectiveness and Safety of Luseogliflozin, Sodium-Glucose Cotransporter2 Inhibitor, to Treat Hyperglycemia in an Acute Stroke Stage

Introduction: Hyperglycemia found at arrival or after admission must be treated as soon as possible in acute stroke patients, because hyperglycemia impairs their clinical outcome. However, it hasn’t been established how to treat it. Hypothesis: Sodium-glucose cotransporter-2 (SGLT2) inhibitors can lower blood glucose level soon and safely in an acute stroke stage. Patients and Methods: We included acute stroke patients 1) who were admitted between September 2015 and June 2017, 2) who could orally take food after admission, 3) who presented fasting blood glucose level of higher than 150 mg/dl on the 3rd day, and 4) who received the SGLT2 inhibitor of luseogliflozin 2.5mg on the 3rd day to lower blood glucose level. We excluded patients undergoing enteral feeding or insulin therapy. We didn’t use sulfonylureas nor glinides. We provided food with appropriate calorie, determined according to Harris-Benedict equation, including carbohydrates (carbo) adjusted to 40% of the target calorie. We evaluated blood glucose level, urine glucose and urine ketones at arrival and on the 6th day. Results: Fifty-six patients matched our criteria. On admission, their average age was 71 years, average body mass index was 24.1 kg/m2, their average HbA1c was 7.6 %, blood glucose level was 192 mg/dl and creatinine clearance was 64.6 ml/min. Patients take food with average 1400 kcal including carbo of 140 g/day. Average three days after starting luseogliflozin treatment, their average fasting blood glucose level was improved to 117 mg/dl, 54 patients (96%) presented positive urine glucose and 29 patients (52%) positive urine ketones. No symptoms of hypoglycemia or ketoacidosis occurred. Conclusion: Luseogliflozin coupled with food including carbo of average 140 g/day could lower blood glucose level soon and safely in acute stroke patients with appropriate conditions.

Abstract 66: Practical Application of Serial Measurement of Cardiac Troponin I for Risk Stratification in Acute Ischemic Stroke

Background: Serum cardiac troponin can be increased in acute ischemic stroke and regarded as a prognostic marker after stroke as similar as coronary artery disease (CAD). However, interpretation of troponin elevation in ischemic stroke patients is complex. Therefore, the aim of this study was to elucidate the possible causes and long-term prognostic value of troponin elevation in ischemic stroke patients. Methods: In a prospective, single center cohort study, we performed serial measurement of serum troponin and 12-lead electrocardiogram (ECG) at 48 hours after stroke onset followed by admission. Based on troponin I level at 48 hours, patients were categorized into 3 groups; elevated (≥0.04 ng/mL), minimally elevated (0.040-0.010 ng/mL) and non-detectable (&lt;0.010 ng/mL) level. Comorbidities with possible impact on troponin elevation were documented based on either historical information or abnormalities in disease-related biomarkers. The primary endpoint was death and major adverse cardiac and cerebrovascular event (MACCE). Results: Among 1092 consecutive patients during 2-year period, 145 patients (13.3%) and 335 patients (30.7%) had a positive and minor elevation troponin. Multivariable analysis identified six-comorbidities included atrial fibrillation (AF), hypertrophic myocardium (HM), heart failure (HF), chronic kidney disease (CKD), active cancer and possibly ischemic heart disease (IHD), and composite neurological factor (defined as moderate to severe deficits or insular lesions) associated with troponin elevation. In a multivariate Cox model, minimally and elevated troponin were independently associated with death (hazard ratio [HR]: 1.77, 95% confidence interval [CI]: 1.07-2.91 for minor elevation and HR: 3.63, 95% CI: 2.13-6.19 for positive troponin) and combined endpoints of MACCE. Conclusions: Troponin elevation even minor elevation are associated with mortality and MACCE in patients with acute stage of ischemic stroke.

What Do Experimental Models Teach Us About Comorbidities in Stroke?

There is a general consensus that animal models do not perfectly represent human conditions. This is not derived from any specific event, such as an ischemic episode, but rather reflects inherent differences in the physiology, anatomy, and metabolism among different species. Disparities among species also arise from differences in assessing functional recovery in stroke. Humans place a priority in regaining function in speech, cognition, and limb control, but these functions are not always readily translatable in animal models. Moreover, because functional recovery depends on the stroke type and location, induction of an ischemic lesion in a predefined area of an animal model, at best, reflects only a subtype of human stroke. Nevertheless, certain clinical pathophysiology features of stroke, such as acute outcomes and inflammatory/immune responses, are shared in animal models.1 Combined with complementary knowledge from in vitro studies, animal models can provide valuable insight into stroke pathology at a systems level. Analyses of translational inefficiencies in stroke model systems have led to the identification of underlying issues, which include, but are not limited to, rigor in experimental design, internal and external validity, negative bias, and insufficient statistical power. Together, these inefficiencies have steered collaborative international efforts in preclinical research to overcome these challenges.2 An additional issue of importance is the insufficient understanding of stroke pathophysiology beyond the acute phase and the primary reliance on infarct volume in reporting acute outcomes. Together with a lack of inclusion of comorbidities in animal models of stroke, the development of clinical protocols based on findings from normal metabolic animals may contribute to translational failures. In light of a recent concerted effort to address the future of translational stroke research,3 this review focuses on underlying translational issues and discusses insights gained from stroke models inclusive of comorbidities in the preclinical literature. ### Stroke Pathology: A Moving Target With Multiple Components Despite …

Increased Inflammatory Response in Old Mice is Associated with More Severe Neuronal Injury at the Acute Stage of Ischemic Stroke.

Stroke occurs mostly in patients with advanced age. Elderly patients have a less favorable prognosis compared with young adult patients. To understand the underlying mechanisms, we tested our hypothesis that an increased inflammatory response to acute ischemic injury in old stroke mice leads to more severe brain damage and behavioral dysfunction. An ischemic stroke model was created in 2- and 12-month-old C57BL/6 mice through permanent occlusion of the left distal middle cerebral artery (dMCAO). Infarct/atrophy volumes were quantified by staining the brain sections with Cresyl Violet. Sensorimotor function was assessed using the corner test and adhesive removal test. Quantification of CD68+ cells in the peri-infarct region was performed at 1, 3 and 14 days after dMCAO. Interleukin-6 (IL-6), interleukin-1 β (IL-1β) and vascular endothelial growth factor (VEGF) levels in the ischemic brain tissue were measured using ELISA. Western blot was used to determine the expression levels of tight junction proteins, claudin-5 and zonula occludens (ZO)-1. Blood-brain barrier permeability was measured by Evans blue (EB) extravasation. Gelatinase B (MMP-9, type IV collagenase) was measured by gel zymography. Compared to 2-month-old mice, 12-month-old mice had more severe behavioral deficits at both the acute and chronic stages of stroke. Compared with the 2-month-old mice, 12-month-old mice had larger infarct/atrophy volumes at 1 and 14 days after dMCAO, higher levels of IL-6 and IL-1β, higher MMP9 activity, and lower levels of claudin-5 and ZO-1 at 1 and 3 days after dMCAO. 12-month-old mice also had more CD68+ cells in the peri-infarct region at 1, 3 and 14 days after dMCAO and more EB leakage at 3 days after dMCAO. A higher inflammatory response at the acute stage of ischemic stroke in old mice is associated with more severe neuronal injury and long-term behavioral dysfunction.

Internal carotid artery repair in acute stage of ischemic stroke after thrombolysis

Internal carotid artery repair in acute stage of ischemic stroke after thrombolysis