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

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

A 35-year-old female visited emergency department for a sudden onset of headache with vomiting after management for abortion at local department. Neurological examination revealed drowsy mentality without focal neurological deficits. CT showed 3.2×3.4 cm hyperdense intraventricular mass with intraventricular hemorrhage. The intraventricular hemorrhage was found in lateral, 3rd, and 4th ventricles. MRI showed well enhancing intraventricular mass abutting choroid plexus in the trigone of the right lateral ventricle. CT angiography showed tortuous prominent arteries from choroidal artery in tumor. Her neurological status deteriorated to stupor and contralateral hemiparesis during planned preoperative workup. Urgent transtemporal and transcortical approach with decompressive craniectomy for removal of intraventricular meningioma with hemorrhage was done. Grossly total removal of ventricular mass was achieved. Pathological finding was meningotheliomatous meningioma of World Health Organization (WHO) grade I. The patient recovered to alert mentality and no motor deficit after intensive care for increased intracranial pressure. However, visual field defect was developed due to posterior cerebral artery territory infarction. The visual deficit did not resolve during follow up period. Lateral ventricular meningioma with spontaneous intraventricular hemorrhage in pregnant woman is very uncommon. We report a surgical case of lateral ventricular meningioma with rapid neurological deterioration for intraventricular hemorrhage.
Adult ; Angiography ; Arteries ; Choroid ; Choroid Plexus ; Critical Care ; Decompressive Craniectomy ; Emergency Service, Hospital ; Female ; Follow-Up Studies ; Fourth Ventricle ; Headache ; Hemorrhage ; Humans ; Infarction ; Intracranial Pressure ; Lateral Ventricles ; Magnetic Resonance Imaging ; Meningioma ; Neurologic Examination ; Paresis ; Posterior Cerebral Artery ; Pregnancy ; Pregnant Women ; Stupor ; Visual Fields ; Vomiting ; World Health Organization

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

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: To determine the correlation between cerebral blood flow (CBF) on arterial spin labeling (ASL) MRI and the degree of postoperative revascularization assessed on digital subtraction angiography in children with moyamoya disease (MMD). MATERIALS AND METHODS: Twenty-one children (9 boys and 12 girls; mean age, 8.4 ± 3.6 years; age range, 3–16 years) with MMD who underwent both pseudocontinuous ASL MRI at 1.5T and catheter angiography before and after superficial temporal artery encephaloduroarteriosynangiosis were included in this retrospective study. The degree of revascularization in the middle cerebral artery (MCA) territory was evaluated on external carotid angiography and was graded on a 3-point scale. On ASL CBF maps, regions of interest were manually drawn over the MCA territory of the operated side at the level of the centrum semi-ovale and over the cerebellum. The normalized CBF (nCBF) was calculated by dividing the CBF of the MCA territory by the CBF of the cerebellum. Changes in nCBFs were calculated by subtracting the preoperative nCBF values from the postoperative nCBF values. The correlation between nCBF changes measured with ASL and the revascularization grade from direct angiography was evaluated. RESULTS: The nCBF value on the operated side increased after the operation (p = 0.001). The higher the degree of revascularization, the greater the nCBF change was: poor revascularization (grade 1), −0.043 ± 0.212; fair revascularization (grade 2), 0.345 ± 0.176; good revascularization (grade 3), 0.453 ± 0.182 (p = 0.005, Jockheere-Terpstra test). The interobserver agreement was excellent for the measured CBF values of the three readers (0.91–0.97). CONCLUSION: The nCBF values of the MCA territory obtained from ASL MRI increased after the revascularization procedure in children with MMD, and the degree of nCBF change showed a significant correlation with the degree of collateral formation evaluated via catheter angiography.
Angiography ; Angiography, Digital Subtraction ; Catheters ; Cerebellum ; Cerebral Revascularization ; Cerebrovascular Circulation ; Child ; Female ; Humans ; Magnetic Resonance Imaging ; Middle Cerebral Artery ; Moyamoya Disease ; Perfusion ; Retrospective Studies ; Temporal Arteries

OBJECTIVE: Coiled aneurysms are known to recanalize over time, making follow-up evaluations mandatory. Although de novo intracranial aneurysms (DNIAs) are occasionally detected during routine patient monitoring, such events have not been thoroughly investigated to date. Herein, we generated estimates of DNIA development during long-term observation of coiled cerebral aneurysms, focusing on incidence and the risk factors involved. MATERIALS AND METHODS: In total, 773 patients undergoing coil embolization of intracranial aneurysms between 2008 and 2010 were reviewed retrospectively. Their medical records and radiologic data accrued over the extended period (mean, 52.7 ± 29.7 months) were analyzed. For the detection of DNIA, follow-up magnetic resonance angiography and/or conventional angiography were used. The incidence of DNIAs and related risk factors were analyzed using Cox proportional hazards regression and Kaplan-Meier product-limit estimator. RESULTS: In 19 (2.5%) of the 773 patients with coiled aneurysms, DNIAs (0.56% per patient-year) developed during continued long-term monitoring (3395.3 patient-years). Of these, 9 DNIAs (47.4%) were detected within 60 months, with 10 (52.6%) emerging thereafter. The most common site involved was the posterior communicating artery (n = 6), followed by the middle cerebral artery (n = 5) and the basilar top (n = 4). Multivariate analysis indicated that younger age (< 50 years) (hazard ratio [HR] = 1.045; p = 0.010) and recanalization of coiled aneurysms (HR = 2.560; p = 0.047) were significant factors in DNIA formation, whereas female sex, smoking, and hypertension fell short of statistical significance. Cumulative survival rates without DNIA were significantly higher in older subjects (> 60 years; p < 0.001) and in the absence of post-coiling aneurysm recurrence (p = 0.006). CONCLUSION: In most patients with coiled aneurysms, development of DNIAs during long-term monitoring is rare. However, younger patients (< 50 years) or patients with recurring aneurysms appear to be predisposed to DNIAs.
Aneurysm ; Angiography ; Arteries ; Embolization, Therapeutic ; Female ; Follow-Up Studies ; Humans ; Hypertension ; Incidence ; Intracranial Aneurysm ; Magnetic Resonance Angiography ; Medical Records ; Middle Cerebral Artery ; Monitoring, Physiologic ; Multivariate Analysis ; Recurrence ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking ; Survival Rate