BACKGROUND: Insufficient cerebral perfusion is suggested to play a role in the development of Alzheimer disease (AD). However, there is a lack of direct evidence indicating whether hypoperfusion causes or aggravates AD pathology. We investigated the effect of chronic cerebral hypoperfusion on AD-related pathology in humans. METHODS: We enrolled a group of cognitively normal patients (median age: 64 years) with unilateral chronic cerebral hypoperfusion. Regions of interest with the most pronounced hypoperfusion changes were chosen in the hypoperfused region and were then mirrored in the contralateral hemisphere to create a control region with normal perfusion. 11C-Pittsburgh compound-positron emission tomography standard uptake ratios and brain atrophy indices were calculated from the computed tomography images of each patient. RESULTS: The median age of the 10 participants, consisting of 4 males and 6 females, was 64 years (47-76 years). We found that there were no differences in standard uptake ratios of the cortex (volume of interest [VOI]: P = 0.721, region of interest [ROI]: P = 0.241) and grey/white ratio (VOI: P = 0.333, ROI: P = 0.445) and brain atrophy indices (Bicaudate, Bifrontal, Evans, Cella, Cella media, and Ventricular index, P > 0.05) between the hypoperfused regions and contralateral normally perfused regions in patients with unilateral chronic cerebral hypoperfusion. CONCLUSION Our findings suggest that chronic hypoperfusion due to large vessel stenosis may not directly induce cerebral β-amyloid deposition and neurodegeneration in humans.
Aged ; Alzheimer Disease/pathology* ; Amyloid beta-Peptides/metabolism* ; Arteries ; Atrophy ; Brain/metabolism* ; Cerebral Cortex/metabolism* ; Cerebrovascular Circulation ; Constriction, Pathologic/pathology* ; Female ; Humans ; Magnetic Resonance Imaging/methods* ; Male ; Middle Aged ; Positron-Emission Tomography/methods*

Objective: Exposure to microgravity results in postflight cardiovascular deconditioning in astronauts. Vascular oxidative stress injury and mitochondrial dysfunction have been reported during this process. To elucidate the mechanism for this condition, we investigated whether mitochondrial oxidative stress regulates calcium homeostasis and vasoconstriction in hindlimb unweighted (HU) rat cerebral arteries. Methods: Three-week HU was used to simulate microgravity in rats. The contractile responses to vasoconstrictors, mitochondrial fission/fusion, Ca Results: An increase of cytoplasmic Ca Conclusion The present results suggest that mitochondrial oxidative stress enhances cerebral vasoconstriction by regulating calcium homeostasis during simulated microgravity.
Animals ; Calcium/metabolism* ; Cerebral Arteries ; Homeostasis ; Male ; Mitochondria/physiology* ; Myocytes, Smooth Muscle/physiology* ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Vasoconstriction/physiology* ; Weightlessness Simulation

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.
Animals ; Brain ; Carotid Arteries ; Cerebral Infarction ; Connexin 43 ; Imatinib Mesylate ; Ischemia ; Learning ; Memory ; Mice ; Motor Activity ; Neuroprotection ; Phosphotransferases ; Reperfusion ; Reperfusion Injury ; STAT3 Transcription Factor ; Transducers ; Walking

The present study was designed to examine whether Ramipril (an inhibitor of angiotensin-converting enzyme) affected spontaneous hypertension-induced injury of cerebral artery by regulating connexin 43 (Cx43) expression. Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were randomly divided into WKY, WKY + Ramipril, SHR, and SHR + Ramipril groups (n = 8). The arterial pressure was monitored by the tail-cuff method, and vascular function in basilar arteries was examined by pressure myography. Hematoxylin-eosin (HE) staining was used to show vascular remodeling. The expression and distribution of Cx43 was determined by using immunofluorescence and immunohistochemistry analysis. The protein and mRNA levels of Cx43 were examined by Western blot and real-time PCR analysis, respectively. The results showed that chronic Ramipril treatment significantly attenuated blood pressure elevation (P < 0.01, n = 8) and blood vessel wall thickness in SHR (P < 0.01, n = 8). The cerebral artery contraction rate in the SHR group was higher than that in the WKY group (P < 0.05, n = 8). The cerebral artery contraction rate in the SHR + Ramipril group was lower than that in the SHR group (P < 0.05, n = 8). Pretreatment with 2-APB (Cx43 non-specific blocker) or Gap26 (Cx43 specific blocker) significantly decreased the vasoconstriction rate, while pretreatment with AAP10 (Cx43 non-specific agonist) significantly increased the vasoconstriction in the SHR + Ramipril group (P < 0.05, n = 8). In addition, the expression of Cx43 mRNA and protein in cerebral arteries of SHR group was higher than that of WKY group (P < 0.05, n = 8). The mRNA and protein expression of Cx43 in cerebral arteries of SHR + Ramipril group was significantly lower than that of SHR group (P < 0.05, n = 8). These results suggest that Ramipril can down-regulate the expression of Cx43 mRNA and protein in cerebral arterial cells of SHR, lower blood pressure, promote vasodilation, and improve arterial damage and vascular dysfunction caused by hypertension.
Animals ; Blood Pressure ; Cerebral Arteries ; drug effects ; metabolism ; Connexin 43 ; metabolism ; Hypertension ; drug therapy ; Ramipril ; pharmacology ; Random Allocation ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Vascular Remodeling

Subarachnoid hemorrhage (SAH) usually occurs due to aneurysmal rupture of intracranial arteries and its typical computed tomography (CT) findings are increased attenuation of cisterns and subarachnoid spaces. However, several CT findings mimicking SAH are feasible in diverse conditions. They are so-called as pseudo-SAH, and this report is a case of pseudo-SAH which is misdiagnosed as aneurysm rupture accompanied by bilateral chronic subdural hematoma (cSDH). A 42-year-old male with severe headache visited our institute. Non-contrast brain CT images showed increased attenuation on basal cistern, and cSDH on both fronto-temporo-parietal convexity with midline shifting. Trans-femoral cerebral angiography was done and we confirmed small aneurysm at right M1 portion of middle cerebral artery. Under diagnosis of SAH, we planned an operation in order to clip aneurysmal neck and remove cSDH. cSDH was removed as planned, however, there was no SAH and we also couldn't find the rupture point of aneurysm. Serial follow-up CT showed mild cumulative cSDH recurrence, but the patient was tolerant and had no neurologic deficit during hospitalization. We have checked the patient via out-patient department for 6 months, there are no significant changes in volume and density of cSDH and the patient also have no neurologic complications.
Adult ; Aneurysm ; Arteries ; Brain ; Brain Edema ; Cerebral Angiography ; Diagnosis ; Follow-Up Studies ; Headache ; Hematoma, Subdural, Chronic ; Hemorrhage ; Hospitalization ; Humans ; Intracranial Hypertension ; Male ; Middle Cerebral Artery ; Neck ; Neurologic Manifestations ; Outpatients ; Recurrence ; Rupture ; Subarachnoid Hemorrhage ; Subarachnoid Space

OBJECTIVE: Endovascular treatment (EVT) outcomes for acute M2 segment of middle cerebral artery occlusion remains unclear because most results are obtained from patients with large artery occlusion in the anterior circulation. The objective of this study was to assess procedural outcomes for acute M2 occlusion and compare outcomes according to thrombus location (M1 vs. M2).METHODS: A systematic review was performed for online literature published from January 2004 to December 2016. Primary outcome was successful recanalization rate and symptomatic intracranial hemorrhage (S-ICH) after the procedure. A fixed effect model was used if heterogeneity was less than 50%.RESULTS: Eight articles were included. EVT showed successful recanalization rate of 69.1% (95% confidence interval [CI], 54.9–80.4%) and S-ICH rate of 6.1% (95% CI, 4.5–8.3%). The rates of good clinical outcome at 3 months and mortality were 59.4% (95% CI, 49.9–68.2%) and 14.9% (95% CI, 11.4–19.3%), respectively. According to thrombus location (M1 vs. M2), successful recanalization (odds ratio [OR], 1.539; 95% CI, 0.293–8.092; p=0.610) and S-ICH (OR, 1.313; 95% CI, 0.603–2.861; p=0.493) did not differ significantly. Good clinical outcome was more evident in M2 occlusion after EVT than that in M1 occlusion (OR, 1.639; 95% CI, 1.135–2.368; p=0.008). However, mortality did not differ significantly according to thrombus location (OR, 0.788; 95% CI, 0.486–1.276; p=0.332).CONCLUSION: EVT seems to be technically feasible for acute M2 occlusion. Direct comparative studies between EVT and medical treatment are needed further to find specific beneficiary group after EVT in patient with M2 occlusion.
Arteries ; Humans ; Infarction ; Infarction, Middle Cerebral Artery ; Intracranial Hemorrhages ; Middle Cerebral Artery ; Mortality ; Population Characteristics ; Stroke ; Thrombectomy ; Thrombosis

OBJECTIVE: This study aimed to analyze intracranial vessels using brain computed tomography angiography (CTA) and scoring systems to diagnose brain death and predict poor neurologic outcomes of postcardiac arrest patients.METHODS: Initial brain CTA images of postcardiac arrest patients were analyzed using scoring systems to determine a lack of opacification and diagnose brain death. The primary outcome was poor neurologic outcome, which was defined as cerebral performance category score 3 to 5. The frequency, sensitivity, specificity, positive predictive value, negative predictive value, and area under receiver operating characteristic curve for the lack of opacification of each vessel and for each scoring system used to predict poor neurologic outcomes were determined.RESULTS: Patients with poor neurologic outcomes lacked opacification of the intracranial vessels, most commonly in the vein of Galen, both internal cerebral veins, and the mid cerebral artery (M4). The 7-score results (P=0.04) and 10-score results were significantly different (P=0.04) between outcome groups, with an area under receiver operating characteristic of 0.61 (range, 0.48 to 0.72). The lack of opacification of each intracranial vessel and all scoring systems exhibited high specificity (100%) and positive predictive values (100%) for predicting poor neurologic outcomes.CONCLUSION: Lack of opacification of vessels on brain CTA exhibited high specificity for predicting poor neurologic outcomes of patients after cardiac arrest.
Angiography ; Brain Death ; Brain ; Cerebral Arteries ; Cerebral Veins ; Heart Arrest ; Humans ; Hypothermia ; ROC Curve ; Sensitivity and Specificity

BACKGROUND: Achondroplasia is one of the most common types of dwarfism and is inherited as an autosomal dominant disease. The patients with achondroplasia suffer from various complications such as craniofacial, central nervous system, spinal, respiratory and cardiac anomalies.CASE DESCRIPTION: We report a case of a 35-year-old man with achondroplasia who visited the emergency room with right hemiplegia and aphasia within 6 hours after onset. An Initial CT angiography showed the total occlusion of a left internal cerebral artery due to the thrombus. We treated the patient with endovascular thrombectomy using “Solumbra technique” with balloon guiding catheter. The procedure was successful and result was completely recanalized with Thrombolysis in Cerebral Infarction (TICI) scale 3 and the weakness also improved from grade II to grade IV.CONCLUSION: Acute ischemic stroke patients with achondroplasia could be treated with mechanical thrombectomy.
Achondroplasia ; Adult ; Angiography ; Aphasia ; Catheters ; Central Nervous System ; Cerebral Arteries ; Cerebral Infarction ; Dwarfism ; Emergency Service, Hospital ; Hemiplegia ; Humans ; Stroke ; Thrombectomy ; Thrombosis

We present the case of a 23-year-old man who suddenly collapsed during a physical altercation with his friends while in a drunken state. The post-mortem computed tomography (CT) with angiography revealed acute basal subarachnoid hemorrhage with rupture of the left middle cerebral artery. On autopsy, the head, face, mandible and neck showed multifocal hemorrhages with fracture of the hyoid bone, and the pathologic findings of the brain was consistent with CT findings. However, the vascular rupture site was not observed macroscopically. On histologic examination, a microscopic focal rupture was identified at the proximal portion of the middle cerebral artery, and possibility of arteriopathy was considered. This case illustrates that other parts of intracerebral arteries (other than the vertebral arteries) can be the culprit of rupture in the case of traumatic basal subarachnoid hemorrhage, and the post-mortem angiographic findings can be helpful in targeting the site of vascular injury. Furthermore, meticulous sampling of intracranial vessels could help find the vascular rupture site and identify any histologic findings suspicious of arteriopathy. Therefore, we suggest that post-mortem angiography can be an effective and adjunctive tool for a tailored approach in finding the vascular injury, and that histologic examination of both the intracranial and extracranial arteries be important to medicolegally ensure the death of traumatic basal subarachnoid hemorrhage and to examine presence of arteriopathy as a predisposing factor.
Angiography ; Arteries ; Autopsy ; Brain ; Causality ; Forensic Pathology ; Friends ; Head ; Hemorrhage ; Humans ; Hyoid Bone ; Mandible ; Middle Cerebral Artery ; Neck ; Rupture ; Subarachnoid Hemorrhage ; Subarachnoid Hemorrhage, Traumatic ; Vascular System Injuries ; Young Adult

BACKGROUND AND PURPOSE: We investigated whether the intracranial arterial calcification status reflects the overall cerebral atherosclerosis burden. METHODS: Patients with acute cerebral infarction who were admitted to a single university hospital stroke center and underwent brain computed tomography angiography (CTA) between May 2011 and December 2015 were included. We reviewed their demographic, clinical, and imaging data. Cerebral artery calcification was assessed from the cavernous portion of both internal carotid arteries, and patients were categorized into three groups according to the calcification status. The cerebral atherosclerosis score was calculated as the sum of the degree of stenosis of the major intracranial and extracranial arteries on brain CTA. RESULTS: In total, 1,161 patients were included (age=67±13 years, mean±standard deviation), of which 517 were female. Intracranial arterial calcification and atherosclerosis were detected in 921 patients. The cerebral atherosclerosis score tended to increase with the calcification status (no calcification=2.0±3.0, mild=3.8±3.8, severe=6.5±4.8; p < 0.001 in analysis of variance followed by the Bonferroni test). Multivariable logistic regression analysis including age, sex, vascular risk factors, body mass index, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and calcification status showed that intracranial calcification was independently associated with an advanced cerebral atherosclerosis burden in a dose-dependent manner (compared to no calcification: odds ratio=2.0 and 95% confidence interval=1.1–3.4 for mild calcification, and odds ratio=4.7 and 95% confidence interval=2.7–8.3 for severe calcification). CONCLUSIONS: This study found that the calcification status of the cavernous portion of an internal carotid artery can reflect the overall cerebral atherosclerosis burden.
Angiography ; Arteries ; Atherosclerosis ; Body Mass Index ; Brain ; C-Reactive Protein ; Carotid Artery, Internal ; Cerebral Arteries ; Cerebral Infarction ; Constriction, Pathologic ; Female ; Glomerular Filtration Rate ; Humans ; Intracranial Arteriosclerosis* ; Logistic Models ; Risk Factors ; Stroke ; Vascular Calcification