Severe ischemic stroke carries a high rate of disability and death. The severity of stroke is often assessed by the degree of neurological deficits or the extent of brain infarct, defined as severe stroke and large infarction, respectively. Critically severe stroke is a life-threatening condition that requires neurocritical care or neurosurgical intervention, which includes stroke with malignant brain edema, a leading cause of death during the acute phase, and stroke with severe complications of other vital systems. Early prediction of high-risk patients with critically severe stroke would inform early prevention and treatment to interrupt the malignant course to fatal status. Selected patients with severe stroke could benefit from intravenous thrombolysis and endovascular treatment in improving functional outcome. There is insufficient evidence to inform dual antiplatelet therapy and the timing of anticoagulation initiation after severe stroke. Decompressive hemicraniectomy (DHC) <48 h improves survival in patients aged <60 years with large hemispheric infarction. Studies are ongoing to provide evidence to inform more precise prediction of malignant brain edema, optimal indications for acute reperfusion therapies and neurosurgery, and the individualized management of complications and secondary prevention. We present an evidence-based review for severe ischemic stroke, with the aims of proposing operational definitions, emphasizing the importance of early prediction and prevention of the evolution to critically severe status, summarizing specialized treatment for severe stroke, and proposing directions for future research.
Humans ; Ischemic Stroke/pathology* ; Brain Edema/surgery* ; Stroke/prevention & control* ; Brain/pathology* ; Brain Infarction/pathology* ; Treatment Outcome

Cerebral ischemia-reperfusion injury(CIRI) is an important factor hindering the recovery of ischemic stroke patients after blood flow recanalization. Mitochondria, serving as the "energy chamber" of cells, have multiple important physiological functions, such as supplying energy, metabolizing reactive oxygen species, storing calcium, and mediating programmed cell death. During CIRI, oxidative stress, calcium overload, inflammatory response, and other factors can easily lead to neuronal mitochondrial dyshomeostasis, which is the key pathological link leading to secondary injury. As reported, the mitochondrial quality control(MQC) system, mainly including mitochondrial biosynthesis, kinetics, autophagy, and derived vesicles, is an important endogenous mechanism to maintain mitochondrial homeostasis and plays an important protective role in the damage of mitochondrial structure and function caused by CIRI. This paper reviewed the mechanism of MQC and the research progress on MQC-targeting therapy of CIRI in recent 10 years to provide theoretical references for exploring new strategies for the prevention and treatment of ischemic stroke with traditional Chinese medicine.
Brain Ischemia/prevention & control* ; Calcium/metabolism* ; Humans ; Ischemic Stroke ; Mitochondria/pathology* ; Reactive Oxygen Species/metabolism* ; Reperfusion Injury/prevention & control*

Stroke classified into ischemic and hemorrhagic subtypes, is among the most devastating diseases for human being. Certain drugs could increase the blood viscosity, thereby increasing the potential risk of ischemia. Anti-platelet and anti-coagulation drugs, as the treatment of first choice, increase the risk of intracranial hemorrhage and death. Here, we are the first to propose the concept of drug-related stroke, and discuss the treatment strategy for patients who are complicated with intracranial hemorrhage or plan to receive neurosurgical operation during either anti-platelet or anti-coagulation medication. We hope to arouse the attention for drug related stroke among the clinicians and offer recommendation for clinical intervention.
Drug-Related Side Effects and Adverse Reactions ; pathology ; Humans ; Intracranial Hemorrhages ; complications ; Stroke ; chemically induced ; prevention & control ; 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

OBJECTIVETo investigate the protective effect of ulinastatin (UTI) against acute lung injury induced by heatstroke in mice.

METHODSSixty C57/BL6 mice were randomly divided into 6 groups, with 10 mice in each: control group, heatstroke group, UTI pretreatment group, saline pretreatment group, UTI post-treatment group, saline post-treatment group. The control mice were housed at a controlled room temperature of (22∓1) degrees; celsius, and the other groups were placed inside a temperature and humidity controlled chamber pre-set at 37 degrees; celsius and 60%. The two UTI groups were intraperitoneally injected with UTI at 5×10(4) U/kg 10 min before or after heat stress, and the two saline groups were given then equal amounts of saline in the same manner. The core body temperature of mice was monitored by a mercury thermometer every 30 min in the first 1.5 h during heating. The core temperature was measured, then every 15 min until it reached 42.7 degrees; celsius, which was taken as the onset of heatstroke. The animals were allowed to recover passively at ambient temperature for 6 h. The lung histopathological changes, protein concentration in BALF, lung wet/dry weight ratios, lung water content, and pulmonary microvascular permeability were assayed after 6 h of recovery at 37 degrees;celsius.

RESULTSCompared with the control group, the heatstroke model group and two saline groups displayed more severe lung damage and pathological morphology changes, and the lung wet/dry weight ratio, protein concentration in BALF, lung water content and pulmonary microvascular permeability were also significantly increased. These effects were significantly alleviated in UTI treated group. Pretreat ment with UTI significantly prolonged the time to Tc≥42.7 degrees; celsius but had no effect on lung injury induced by heatstroke.

CONCLUSIONUTI can reduce the pulmonary edema and inflammatory exudation in acute lung injury caused by heatstroke.

Acute Lung Injury ; drug therapy ; physiopathology ; Animals ; Body Temperature ; Bronchoalveolar Lavage Fluid ; chemistry ; Edema ; prevention & control ; Glycoproteins ; therapeutic use ; Heat Stroke ; physiopathology ; Lung ; pathology ; Mice ; Mice, Inbred C57BL

Cardiac embolism continues to be a leading etiology of ischemic strokes worldwide. Although pathologies that result in cardioembolism have not changed over the past decade, there have been significant advances in the treatment and stroke prevention methods for these conditions. Atrial fibrillation remains the prototypical cause of cardioembolic strokes. The availability of new long-term monitoring devices for atrial fibrillation detection such as insertable cardiac monitors has allowed accurate detection of this leading cause of cardioembolism. The non-vitamin K antagonist oral anticoagulants have improved our ability to prevent strokes for many patients with non-valvular atrial fibrillation (NVAF). Advances in left atrial appendage closure and the U.S. Food and Drug Administration approval of the WATCHMAN (Boston Scientific) device for stroke prevention in NVAF patients who have an appropriate rationale for a nonpharmacological alternative, have revolutionized the field and provided a viable option for patients at higher hemorrhagic risk. The role of patent foramen ovale closure for secondary prevention in selected patients experiencing cryptogenic ischemic strokes at a relatively young age has become clearer thanks to the very recent publication of long-term outcomes from three major studies. Advances in the management of infective endocarditis, heart failure, valvular diseases, and coronary artery disease have significantly changed the management of such patients, but have also revealed new concerns related to assessment of ischemic versus hemorrhagic risk in the setting of antithrombotic use. The current review article aims to discuss these advances especially as they pertain to the stroke neurology practice.
Anticoagulants ; Atrial Appendage ; Atrial Fibrillation ; Coronary Artery Disease ; Embolism ; Endocarditis ; Foramen Ovale, Patent ; Heart Failure ; Humans ; Neurology ; Pathology ; Publications ; Secondary Prevention ; Stroke* ; United States Food and Drug Administration

The present study is to assess the prophylactic effect of quinacrine (QA) , an anti-malarial drug, against heatstroke in rats. Conscious rats were orally given equal volume normal saline or QA (dissolved in normal saline and final dosage for rats was 4.5, 9.0 and 18 mg x kg(-1)). An hour later rats were put into a warm water circulated hot chamber (41.0 +/- 0.5) degrees C. Rectal temperature (core temperature, T(co)) of rats in hot chamber was continuously monitored by a thermocouple. T(co) and survival time of rats showed that QA pre-treatment postponed the hyperthermia, and increased the survival time of rats in hot chamber. Primary striatum neurons' culture from new born rats was maintained with D-MEM and 10% FBS. After immuno-cytochemistry identification with antibodies against neural specific proteins, culture received 20 micromol x L(-1) QA only for 1 h and followed by 43.0 degrees C heat treatment for another hour, or 20 micromol x L(-1) QA for 1 h followed by 43.0 degrees C heat treatment for another hour. Control culture received heat treatment only. Cultures were labeled with the fluorescent indicator DPH and the relative membrane fluidity of neurons was measured with the help of fluorescent polarized spectrophotometer. [3H] Arachidonic acid (AA) labeled membrane of E. Coli cells was used as substrate to determine cPLA2 activity of neurons. Gas chromatography and mass spectrum were also employed to detect on the level of fatty acids level in rat striatum neurons. Results from cells indicated that inhibition of cPLA2, reduction the release of active fatty acids such as AA, and possibly, stabilization of the cell membrane which was disturbed by hot treatment, may contribute to the mechanism underlying heat protection and heatstroke preventive effects of quinacrine.
Animals ; Cells, Cultured ; Corpus Striatum ; drug effects ; pathology ; Fatty Acids ; metabolism ; Heat Stroke ; metabolism ; physiopathology ; prevention & control ; Hot Temperature ; adverse effects ; Male ; Membrane Fluidity ; drug effects ; Neurons ; enzymology ; metabolism ; physiology ; Phospholipases A2 ; metabolism ; Quinacrine ; pharmacology ; Rats ; Rats, Wistar

Periodontal disease is a predictor of stroke and cognitive impairment. The association between the number of lost teeth (an indicator of periodontal disease) and silent infarcts and cerebral white matter changes on brain CT was investigated in community-dwelling adults without dementia or stroke. Dental examination and CT were performed in 438 stroke- and dementia-free subjects older than 50 yr (mean age, 63 +/- 7.9 yr), who were recruited for an early health check-up program as part of the Prevention of Stroke and Dementia (PRESENT) project between 2009 and 2010. In unadjusted analyses, the odds ratio (OR) for silent cerebral infarcts and cerebral white matter changes for subjects with 6-10 and > 10 lost teeth was 2.3 (95% CI, 1.38-4.39; P = 0.006) and 4.2 (95% CI, 1.57-5.64; P < 0.001), respectively, as compared to subjects with 0-5 lost teeth. After adjustment for age, education, hypertension, diabetes mellitus, hyperlipidemia, and smoking, the ORs were 1.7 (95% CI, 1.08-3.69; P = 0.12) and 3.9 (95% CI, 1.27-5.02; P < 0.001), respectively. These findings suggest that severe tooth loss may be a predictor of silent cerebral infarcts and cerebral white matter changes in community-dwelling, stroke- and dementia-free adults.
Age Factors ; Aged ; Alzheimer Disease/diagnosis ; Brain/*radiography ; Cross-Sectional Studies ; Dementia/pathology/prevention & control ; Diabetes Complications/diagnosis ; Female ; Humans ; Hyperlipidemias/complications ; Hypertension/complications ; Interviews as Topic ; Male ; Middle Aged ; Odds Ratio ; Periodontal Diseases/complications/*diagnosis ; Predictive Value of Tests ; Risk Factors ; Stroke/pathology/prevention & control ; Tomography, X-Ray Computed ; Tooth Loss