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

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

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

Distal intracranial occlusions can sometimes cause significant neurological deficits. Endovascular thrombectomy in these vessels may improve outcome but carry a higher risk of haemorrhagic complications due to the small calibre and tortuosity of the target vessel. We report two cases of isolated M2/3 artery occlusion causing dense hemiplegia that was successfully treated with stent retrieval thrombectomy. A “semi-deployment technique” of a 3 mm stentriever was employed at the M2/3 bifurcation of the middle cerebral artery. Partial stent unsheathing allowed adequate clot engagement while avoiding excessive tension by the stent metal struts along the tortuous course of a distal vessel. Complete revascularization was achieved after first-pass of the stent retriever without complication, resulting in good clinical outcome in both cases. The described semi-deployment technique reduces the radial and tractional force exerted by the stentreiver on small branches, and may reduce the risk of vessel laceration or dissection in distal vessel thrombectomy.
Arteries ; Endovascular Procedures ; Hemiplegia ; Lacerations ; Middle Cerebral Artery ; Stents ; Stroke ; Thrombectomy ; Traction

PURPOSE: Mechanical thrombectomy has become the standard of care for acute stroke caused by large vessel occlusion. As more patients are treated endovascularly, the number of older patients with tortuous vessels has risen. In these patients, catheterizing the internal carotid artery via a transfemoral approach can be very difficult or even impossible. Therefore, in selected patients, alternative strategies to the transfemoral approach have to be applied. MATERIALS AND METHODS: We report a case series of six patients undergoing mechanical thrombectomy via a combined transfemoral and transcarotid approach. Puncture of the carotid artery was conducted using roadmap guidance after an unsuccessful transfemoral attempt. Technical aspects and outcomes with this alternative approach were analyzed. RESULTS: Direct puncture of the carotid artery was achieved in five out of six patients (83%). In three out of six patients (50%), revascularization (modified Thrombolysis in Cerebral Infarction score ≥2b) was restored. No complications related to endovascular therapy were documented. One patient showed good neurological outcome (modified Rankin Scale [mRS] 5 at admission, mRS 1 at discharge). CONCLUSION: A combined transfemoral/transcarotid approach can be an alternative vascular access in patients with problematic vessel anatomy.
Carotid Arteries ; Carotid Artery, Internal ; Catheters ; Cerebral Infarction ; Humans ; Punctures ; Standard of Care ; Stroke ; Thrombectomy