scholarly journals An Imbalance Between RAGE/MR/HMGB1 and ATP1α3 is Associated with Inflammatory Changes in Rat Brain Harboring Cerebral Aneurysms Prone to Rupture

2021 ◽  
Author(s):  
Eiji Shikata ◽  
Takeshi Miyamoto ◽  
Tadashi Yamaguchi ◽  
Izumi Yamaguchi ◽  
Hiroshi Kagusa ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Morphological Changes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Cerebral Aneurysms ◽  
Vessel Diameter ◽  
Female Rats ◽  
Standard Diet ◽  
Mrna Levels ◽  
Inflammatory Changes

Abstract Background and Purpose: An aneurysmal subarachnoid hemorrhage is a devastating event. To establish an effective therapeutic strategy, its pathogenesis must be clarified, particularly the pathophysiology of brain harboring intracranial aneurysms (IAs). To elucidate the pathology in brain harboring IAs, we examined the significance of the receptor for advanced glycation end-products (RAGE)/mineralocorticoid receptor (MR) pathway and Na+/K+-ATPase (ATP1α3).Methods: Ten-week-old female rats were subjected to oophorectomy as well as hypertension and hemodynamic changes to induce IAs, and were fed a high-salt diet. Brain damage in these rats was assessed by inflammatory changes in comparison to sham-operated rats fed a standard diet.Results: Six weeks after IA induction (n = 30), irregular morphological changes, i.e., an enlarged vessel diameter and vascular wall, were observed in all of the left posterior cerebral arteries (Lt PCAs) prone to rupture. Approximately 20% of rats had ruptured IAs within 6 weeks. In brain harboring unruptured IAs at the PCA, the mRNA levels of RAGE and MR were higher, and that of ATP1α3 was lower than those in the sham-operated rats (p < 0.05, each). Immunohistochemically, elevated expression of RAGE and MR, and decreased expression of ATP1α3 were observed in the brain parenchyma adjacent to the Lt PCA, resulting in increased Iba-1 and S100B expression that reflected the inflammatory changes. There was no difference between the unruptured and ruptured aneurysm rat groups. Treatment with the MR antagonist esaxerenone abrogated these changes, and led to cerebral and vascular normalization and prolonged subarachnoid hemorrhage-free survival (p < 0.05).Conclusion: Regulation of the imbalance between the RAGE/MR pathway and ATP1α3 may help attenuate the damage in brain harboring IAs, and further studies are warranted to clarify the significance of the down-regulation of the MR/RAGE pathway and the up-regulation of ATP1α3 for attenuating the pathological changes in brain harboring IAs.

scholarly journals Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 598-604
Author(s):  
Valentina Opancina ◽  
Snezana Lukic ◽  
Slobodan Jankovic ◽  
Radisa Vojinovic ◽  
Milan Mijailovic
Keyword(s):  
Risk Factors ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Medical Center ◽  
White Blood Cells ◽  
Cerebral Aneurysms ◽  
International Normalized Ratio ◽  
Cross Sectional Study ◽  
Cross Sectional

AbstractIntroductionAneurysmal subarachnoid hemorrhage is a type of spontaneous hemorrhagic stroke, which is caused by a ruptured cerebral aneurysm. Cerebral vasospasm (CVS) is the most grievous complication of subarachnoid hemorrhage (SAH). The aim of this study was to examine the risk factors that influence the onset of CVS that develops after endovascular coil embolization of a ruptured aneurysm.Materials and methodsThe study was designed as a cross-sectional study. The patients included in the study were 18 or more years of age, admitted within a period of 24 h of symptom onset, diagnosed and treated at a university medical center in Serbia during a 5-year period.ResultsOur study showed that the maximum recorded international normalized ratio (INR) values in patients who were not receiving anticoagulant therapy and the maximum recorded white blood cells (WBCs) were strongly associated with cerebrovascular spasm, increasing its chances 4.4 and 8.4 times with an increase of each integer of the INR value and 1,000 WBCs, respectively.ConclusionsSAH after the rupture of cerebral aneurysms creates an endocranial inflammatory state whose intensity is probably directly related to the occurrence of vasospasm and its adverse consequences.

Evaluation of Vasospasm after Subarachnoid Hemorrhage by Use of Multislice Computed Tomographic Angiography

Neurosurgery ◽  
2002 ◽  
Vol 51 (4) ◽  
pp. 939-943 ◽  
Author(s):  
Yasunari Otawara ◽  
Kuniaki Ogasawara ◽  
Akira Ogawa ◽  
Makoto Sasaki ◽  
Kei Takahashi
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Computed Tomographic Angiography ◽  
Computed Tomographic ◽  
Tomography System ◽  
Middle Cerebral Arteries ◽  
Multislice Images ◽  
Tomographic Angiography

Abstract OBJECTIVE Multislice computed tomographic angiography (CTA) can provide clearer vascular images, even of the peripheral arteries, than conventional CTA. Multislice CTA was compared with digital subtraction angiography (DSA) for the detection of cerebral vasospasm in patients with acute aneurysmal subarachnoid hemorrhage (SAH) to analyze whether multislice CTA can replace DSA in the detection of vasospasm after SAH. METHODS Within 72 hours after the onset of symptoms, multislice CTA and DSA were performed in 20 patients with SAH. Multislice CTA and DSA were repeated on Day 7 to assess cerebral vasospasm. Regions of interest were established in the proximal and distal segments of the anterior and middle cerebral arteries on both multislice CTA and DSA images, and the agreement between the severity of vasospasm on multislice CTA and DSA images was statistically compared. The multislice Aquilon computed tomography system (Toshiba, Inc., Tokyo, Japan) used the following parameters: 1 mm collimation and 3.5 mm per rotation table increment (pitch, 3.5). RESULTS The degree of vasospasm as revealed by multislice CTA correlated significantly with the degree of vasospasm revealed by DSA (P &lt; 0.0001). The agreement between the severity of vasospasm on multislice images obtained via CTA and DSA in the overall, proximal, and distal segments of the cerebral arteries was 91.6, 90.8, and 92.3%, respectively. CONCLUSION Multislice CTA can detect angiographic vasospasm after SAH with accuracy equal to that of DSA.

Equal contribution of increased intracranial pressure and subarachnoid blood to cerebral blood flow reduction and receptor upregulation after subarachnoid hemorrhage

2009 ◽  
Vol 111 (5) ◽  
pp. 978-987 ◽  
Author(s):  
Saema Ansar ◽  
Lars Edvinsson
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Intracranial Pressure ◽  
Sham Group ◽  
Cerebral Arteries ◽  
Mrna Levels ◽  
Saline Injection ◽  
Receptor Upregulation ◽  
Subarachnoid Blood

Object Cerebral ischemia remains the key cause of disability and death in the late phase after subarachnoid hemorrhage (SAH), and its pathogenesis is still poorly understood. The purpose of this study was to examine whether the change in intracranial pressure or the extravasated blood causes the late cerebral ischemia and the upregulation of receptors or the cerebral vasoconstriction observed following SAH. Methods Rats were allocated to 1 of 3 experimental conditions: 1) cisternal injection of 250 μl blood (SAH Group), 2) cisternal injection of 250 μl NaCl (Saline Group), or 3) the same procedure but without fluid injection (Sham Group). Two days after the procedure, the basilar and middle cerebral arteries were harvested, and contractile responses to endothelin (ET)–1 and 5-carboxamidotryptamine (5-CT) were investigated by means of myography. In addition, real-time polymerase chain reaction was used to determine the mRNA levels for ETA, ETB, and 5-HT1 receptors. Regional and global cerebral blood flow (CBF) were quantified by means of an autoradiographic technique. Results Compared with the sham condition, both SAH and saline injection resulted in significantly enhanced contraction of cerebral arteries in response to ET-1 and 5-CT. Regional and global CBF were reduced both in the Saline and SAH groups compared with the Sham Group. The mRNA levels for ETB and 5-HT1B receptors were upregulated after SAH and saline injection compared with the sham procedure. The effects in all parameters were more pronounced for SAH than for saline injection. Conclusions This study revealed that both the elevation of intracranial pressure and subarachnoid blood per se contribute approximately equally to the late CBF reductions and receptor upregulation following SAH.

Detection of Microemboli by Transcranial Doppler Ultrasonography in Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2002 ◽  
Vol 50 (5) ◽  
pp. 1026-1031 ◽  
Author(s):  
Jose G. Romano ◽  
Alejandro M. Forteza ◽  
Mauricio Concha ◽  
Sebastian Koch ◽  
Roberto C. Heros ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Transcranial Doppler ◽  
Doppler Ultrasonography ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Statistical Significance ◽  
Cerebral Arteries ◽  
Transcranial Doppler Ultrasonography ◽  
Control Subjects

Abstract OBJECTIVE: To determine the frequency and characteristics of microembolic signals (MES) in subarachnoid hemorrhage (SAH). METHODS: Twenty-three patients with aneurysmal SAH were monitored with transcranial Doppler ultrasonography for the presence of MES and vasospasm. Each middle cerebral artery was monitored for 30 minutes three times each week. Patients were excluded if they had traumatic SAH or cardiac or arterial sources of emboli. Monitoring was initiated 6.3 days (1–16 d) after SAH and lasted 6.6 days (1–13 d). Eleven individuals without SAH or other cerebrovascular diseases who were treated in the same unit served as control subjects. Each patient underwent monitoring of both middle cerebral arteries a mean of three times; therefore, 46 vessels were studied (a total of 138 observations). Control subjects underwent assessment of each middle cerebral artery once, for a total of 22 control vessels. RESULTS: MES were detected for 16 of 23 patients (70%) and 44 of 138 patient vessels (32%) monitored, compared with 2 of 11 control subjects (18%) and 2 of 22 control vessels (9%) (P &lt; 0.05). MES were observed for 83% of patients with clinical vasospasm and 54% of those without clinical vasospasm. Ultrasonographic vasospasm was observed for 71 of 138 vessels monitored; MES were observed for 28% of vessels with vasospasm and 36% of those without vasospasm. Aneurysms proximal to the monitored artery were identified in 38 of 138 vessels, of which 34% exhibited MES, which is similar to the frequency for vessels without proximal aneurysms (31%). Coiled, clipped, and unsecured aneurysms exhibited similar frequencies of MES. CONCLUSION: MES were common in SAH, occurring in 70% of cases of SAH and one-third of all vessels monitored. Although MES were more frequent among patients with clinical vasospasm, this difference did not reach statistical significance. We were unable to demonstrate a relationship between ultrasonographic vasospasm and MES, and the presence of a proximal secured or unsecured aneurysm did not alter the chance of detection of MES. Further studies are required to determine the origin and clinical relevance of MES in SAH.

ENDOVASCULAR AND SURGICAL TREATMENT OF RUPTURED CEREBRAL ANEURYSMS IN PEDIATRIC PATIENTS

Neurosurgery ◽  
2008 ◽  
Vol 63 (5) ◽  
pp. 859-866 ◽  
Author(s):  
Michael F. Stiefel ◽  
Gregory G. Heuer ◽  
Anuj K. Basil ◽  
John B. Weigele ◽  
Leslie N. Sutton ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Clinical Condition ◽  
Pediatric Patients ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multidisciplinary Treatment ◽  
Cerebral Aneurysms ◽  
Posterior Circulation ◽  
Anterior Circulation ◽  
Fisher Grade ◽  
Good Clinical Condition

Abstract OBJECTIVE Pediatric cerebral aneurysms are rare. There are very few recent studies that focus on the multidisciplinary treatment of ruptured aneurysms. We reviewed our pediatric endovascular and surgical experience with ruptured cerebral aneurysms. METHODS Pediatric patients aged 16 years and younger who were admitted with a diagnosis of aneurysmal subarachnoid hemorrhage and treated at the Children's Hospital of Philadelphia were included in this analysis. RESULTS Twelve patients with 13 aneurysms (4 male patients and 8 female patients; age range, 4 months–16 years; mean age, 5.1 years), were admitted with subarachnoid hemorrhage during the past 12 years. The majority of patients were admitted in good clinical condition; 31% were in Hunt and Hess Grade II, and 31% were in Hunt and Hess Grade III. The remaining patients were in poor clinical condition and were in Hunt and Hess Grade IV (23%) or Grade V (15%). Computed tomography revealed that 15% of the patients were in Fisher Grade 2, 23% were in Fisher Grade 3, and 62% were in Fisher Grade 4. Endovascular techniques were used in the treatment of 5 aneurysms, and microsurgery was used in the treatment of 8 aneurysms. In the endovascular group, aneurysm sizes ranged from 2 to 35 mm (mean, 12.6 mm); 3 aneurysms were in the anterior circulation, and 2 were in the posterior circulation. In the microsurgery group, 6 aneurysms were in the anterior circulation, and 2 were in the posterior circulation; sizes ranged from 3 to 15 mm (mean, 6.8 mm). Sixty-nine percent of the patients were independent at follow-up. CONCLUSION Contemporary endovascular and microsurgical techniques can be used effectively to treat ruptured cerebral aneurysms in pediatric patients. In the time period studied, the techniques were equally effective when used in the appropriate patients.

The significance of morphological changes in cerebral arteries after subarachnoid hemorrhage

1990 ◽  
Vol 72 (4) ◽  
pp. 626-633 ◽  
Author(s):  
Marc R. Mayberg ◽  
Tomohisa Okada ◽  
Don H. Bark
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Whole Blood ◽  
Vessel Wall ◽  
Structural Changes ◽  
Morphological Changes ◽  
Cerebral Arteries ◽  
Cross Sectional Area ◽  
Ultrastructural Changes ◽  
Sectional Area ◽  
Cross Sectional

✓ A porcine model was developed to allow quantitative assessment of morphological changes in cerebral arteries after subarachnoid hemorrhage and to determine the significance of structural changes in producing arterial narrowing. Whole blood was selectively applied to the middle cerebral artery (MCA) of seven pigs. After 10 days, vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. The MCA's exposed to whole blood for 10 days showed prominent luminal narrowing associated with profound ultrastructural changes affecting all layers of the vessel wall. Morphometric analysis, however, demonstrated that significant reductions in the luminal cross-sectional area (−55.8% ± 12.5%, p < 0.005) and increases in radial wall thickness (75.1% ± 10.5%, p < 0.005) were associated with only minimal increase in the cross-sectional area of the vessel wall (12.5% ± 15%,p < 0.025). By stereological analysis, the volume density of individual components of the arterial wall was unchanged in MCA's exposed to blood. Vessels exposed to blood showed a 44% reduction in smooth-muscle cell immunoreactive actin and increased collagen in the extracellular matrix of the vessel wall. These data suggest that structural changes in cerebral arteries after subarachnoid hemorrhage do not directly contribute to vessel narrowing through increases in wall mass. Nevertheless, such changes may reflect pathological mechanisms which act to augment prolonged vasoconstriction or inhibit the maintenance of normal vascular tone.

The Natural History of Cerebral Aneurysms

2017 ◽  
Author(s):  
David Hasan
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Morbidity And Mortality ◽  
Neurological Dysfunction ◽  
Contributing Factors ◽  
Intracellular Adhesion Molecule ◽  
History Of ◽  
Very High

Subarachnoid hemorrhage (SAH) secondary to rupture of cerebral aneurysms represents a relatively small fraction of strokes (5%) but morbidity and mortality associated with aneurysm rupture remain very high despite advances in the treatment of aneurysmal SAH. Cerebral vasospasm (CV) is the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage, as well as delayed neurological dysfunction 1 to 2 weeks after rupture. Endothelial dysfunction is one of the primary contributing factors to CV following aneurysmal SAH, and this is associated with alterations in intracellular adhesion molecule-1 (ICAM-1), matrix metalloproteinases (MM), and the blood-brain barrier[p63].

scholarly journals Morphological changes of intracranial pressure quantifies vasodilatory effect of verapamil to treat cerebral vasospasm

2020 ◽  
Vol 12 (8) ◽  
pp. 802-808 ◽  
Author(s):  
Xiuyun Liu ◽  
Jeffrey R Vitt ◽  
Steven W Hetts ◽  
Koa Gudelunas ◽  
Nhi Ho ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Cerebral Vasospasm ◽  
Morphological Changes ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Delayed Cerebral Ischemia ◽  
Continuous Assessment ◽  
Cerebral Vasoconstriction ◽  
Before And After ◽  
Cerebral Vasodilation

IntroductionAfter aneurysmal subarachnoid hemorrhage (SAH), both proximal and distal cerebral vasospasm can contribute to the development of delayed cerebral ischemia. Intra-arterial (IA) vasodilators are a mainstay of treatment for distal arterial vasospasm, but no methods of assessing the efficacy of interventions in real time have been established.ObjectiveTo introduce a new method for continuous intraprocedural assessment of endovascular treatment for cerebral vasospasm.MethodsThe premise of our approach was that distal cerebral arterial changes induce a consistent pattern in the morphological changes of intracranial pressure (ICP) pulse. This premise was demonstrated using a published algorithm in previous papers. In this study, we applied the algorithm to calculate the likelihood of cerebral vasodilation (VDI) and cerebral vasoconstriction (VCI) from intraprocedural ICP signals that are synchronized with injection of the IA vasodilator, verapamil. Cerebral blood flow velocities (CBFVs) on bilateral cerebral arteries were studied before and after IA therapy.Results192 recordings of patients with SAH were reviewed, and 27 recordings had high-quality ICP waveforms. The VCI was significantly lower after the first verapamil injection (0.47±0.017) than VCI at baseline (0.49±0.020, p<0.001). A larger dose of injected verapamil resulted in a larger and longer VDI increase. CBFV of the middle cerebral artery increases across the days before the injection of verapamil and decreases after IA therapy.ConclusionThis study provides preliminary validation of an algorithm for continuous assessment of distal cerebral arterial changes in response to IA vasodilator infusion in patients with vasospasm and aneurysmal SAH.

Predicting Delayed Ischemic Deficits after Aneurysmal Subarachnoid Hemorrhage Using a Transient Hyperemic Response Test of Cerebral Autoregulation

Neurosurgery ◽  
2000 ◽  
Vol 47 (4) ◽  
pp. 819-826 ◽  
Author(s):  
Joseph M. K. Lam ◽  
Peter Smielewski ◽  
Marek Czosnyka ◽  
John D. Pickard ◽  
Peter J. Kirkpatrick
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Transcranial Doppler ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Neurological Deficits ◽  
Fisher Exact Test ◽  
Exact Test ◽  
Response Test ◽  
Baseline Values ◽  
Hyperemic Response

Abstract OBJECTIVE To assess whether the development of delayed ischemic deficits (DIDs) after aneurysmal subarachnoid hemorrhage can be predicted using transcranial Doppler ultrasonography and the transient hyperemic response test (THRT). METHODS An increase in the middle cerebral artery peak flow velocity (FV) of more than 9% of baseline values after 5 to 9 seconds of carotid artery compression was defined as a normal THRT result, indicating good autoregulatory reserve. The transcranial Doppler criteria for vasospasm were a FV of more than 120 cm/s and a Lindegaard ratio of more than 3. Twenty patients with no immediate postoperative neurological deficits were studied. The FVs at all of the major cerebral arteries were measured daily after surgery, and the THRT results were assessed bilaterally. RESULTS Five of six patients with abnormal THRT results in the first examination after surgery (primary THRT impairment) developed DIDs; none of the remaining patients developed DIDs (Fisher exact test, P = 0.0004). All five patients with DIDs initially exhibited low FVs but all subsequently developed increases in FVs to values of more than 150 cm/s and four exhibited FVs of more than 200 cm/s. The time of onset of DIDs corresponded to the time of onset of moderate vasospasm (FV &gt; 150 cm/s). None of the patients with initially normal THRT results developed DIDs, although four patients did exhibit late (secondary) THRT impairment, which was associated with FVs of more than 120 cm/s. CONCLUSION When the effects of primarily impaired (after surgery) autoregulation are magnified by vasospasm, the risk of DIDs seems to be very high. Vasospasm alone does not seem to cause DIDs. The development of DIDs could therefore be predicted using the THRT for patients after aneurysm clipping.

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