Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
Brain Ischemia/pathology* ; Cell Death ; Humans ; Ischemic Stroke ; Reperfusion Injury/pathology* ; Stroke/pathology* ; Tissue Plasminogen Activator/therapeutic use*

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*

OBJECTIVE: We wanted to differentiate between transient ischemic attack (TIA) and minor stroke using fractional anisotropy and three-dimensional (3D) fiber tractography. MATERIALS AND METHODS: The clinical data, conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) were obtained for 45 TIA patients and 33 minor stroke patients. The fractional anisotrophy ratio (rFA) between the lesion and the mirrored corresponding contralateral normal tissue was calculated and analyzed. The spatial relationship between the lesion and the corticospinal tract (CST) was analyzed and the lesion sizes in the minor stroke patients and TIA patients were compared. RESULTS: Twenty-two of the 45 TIA patients (49%) revealed focal abnormalities following DWI. The rFA was significantly lower (p < 0.05) in the stroke patients (0.71 +/- 0.29) compared to that of the TIA patients (1.05 +/- 0.37). The CST was involved in almost all stroke lesions, but it was not involved in 68% of the TIA lesions. The TIA patients had significantly lower CST injury scores (3.25 +/- 1.75) than did the stroke patients (8.80 +/- 2.39) (p = 0.004). CONCLUSION: Our data indicate that TIA and minor stroke can be identified by analyzing the rFA and the degree of CST involvement, and this may also allow more accurate prediction of a patient's long-term recovery or disability.
Aged ; Anisotropy ; Area Under Curve ; Chi-Square Distribution ; Diagnosis, Differential ; Diffusion Tensor Imaging/*methods ; Female ; Humans ; Image Interpretation, Computer-Assisted ; *Imaging, Three-Dimensional ; Ischemic Attack, Transient/*pathology ; Male ; Middle Aged ; ROC Curve ; Sensitivity and Specificity ; Stroke/*pathology

BACKGROUND: Several western studies have found an occurrence of abnormal angiographic findings in 60-80% of patients with carotid artery territory transient ischemic attack(below carotid TIA) and showed that the location of pathology was frequent in extracranial portion of carotid artery. No accurate studies have been accomplished in our country and some racial differences may exist. So we studied the angiographic findings in patients with carotid TIA. METHODS: Thirty two patients with carotid TIA were included, but patients with non-atherosclerotic origin were excluded. MRI and MRA were checked simultaneously in all patients within 7 days after the last TIA. We evaluated the location, type and degree of the angiographic abnormalities and defined clinical factors related to the presence of vascular lesions. The criteria of significant abnormal findings were stenosis of more than 50%, ulceration or irregularity of carotid territory arteries contralateral to clinical symptoms. RESULTS: Thirteen(40.6%) patients showed significant angiographic abnormalities related with the symptoms of TIA, and M1 portion of middle cerebral artery was the most frequent site, in 7 of 13 patients(53%). Patients with TIAs lasted less than 30 min.(P=0.011) and with TIAs occurred more than 4 times a day(P=0.029), had more frequent angiographic abnormalities. But there were no significant differences according to the presence of related acute cerebral infarction, gender and risk factors of stroke. CONCLUSIONS: In our study, the prevalence of angiographic abnormality and the location of vascular lesion were concordant with the Japanese studies but quite different with the western studies, and we suggest that this may be due to differences in dietary life and race.
Angiography* ; Arteries ; Asian Continental Ancestry Group ; Carotid Arteries ; Cerebral Infarction ; Constriction, Pathologic ; Continental Population Groups ; Humans ; Ischemic Attack, Transient* ; Magnetic Resonance Imaging ; Middle Cerebral Artery ; Pathology ; Prevalence ; Risk Factors ; Stroke ; Ulcer

OBJECTIVE: The purpose of this study was to correlate permeability parameters measured with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a clinical 3-tesla scanner with extravasation of Evans blue in a rat model with transient cerebral ischemia. MATERIALS AND METHODS: Sprague-Dawley rats (n = 13) with transient middle cerebral artery occlusion were imaged using a 3-tesla MRI with an 8-channel wrist coil. DCE-MRI was performed 12 hours, 18 hours, and 36 hours after reperfusion. Permeability parameters (K(trans), v(e), and v(p)) from DCE-MRI were calculated. Evans blue was injected after DCE-MRI and extravasation of Evans blue was correlated as a reference with the integrity of the blood-brain barrier. Correlation analysis was performed between permeability parameters and the extravasation of Evans blue. RESULTS: All permeability parameters (K(trans), v(e), and v(p)) showed a linear correlation with extravasation of Evans blue. Among them, K(trans) showed highest values of both the correlation coefficient and the coefficient of determination (0.687 and 0.473 respectively, p < 0.001). CONCLUSION: Permeability parameters obtained by DCE-MRI at 3-T are well-correlated with Evans blue extravasation, and K(trans) shows the strongest correlation among the tested parameters.
Animals ; Blood-Brain Barrier/pathology ; Capillary Permeability ; Contrast Media ; Disease Models, Animal ; Evans Blue/analysis ; Ischemic Attack, Transient/*diagnosis ; Magnetic Resonance Imaging/instrumentation/*methods ; Male ; Rats ; Rats, Sprague-Dawley ; Stroke/diagnosis