scholarly journals Requisite ischemia for spreading depolarization occurrence after subarachnoid hemorrhage in rodents

2016 ◽  
Vol 37 (5) ◽  
pp. 1829-1840 ◽  
Author(s):  
Fumiaki Oka ◽  
Ulrike Hoffmann ◽  
Jeong Hyun Lee ◽  
Hwa Kyoung Shin ◽  
David Y Chung ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Laser Speckle ◽  
Neurological Outcomes ◽  
Spreading Depolarization ◽  
Arterial Blood ◽  
Electrophysiological Recordings ◽  
Ischemic Tissue

Spontaneous spreading depolarizations are frequent after various forms of human brain injury such as ischemic or hemorrhagic stroke and trauma, and worsen the outcome. We have recently shown that supply-demand mismatch transients trigger spreading depolarizations in ischemic stroke. Here, we examined the mechanisms triggering recurrent spreading depolarization events for many days after subarachnoid hemorrhage. Despite large volumes of subarachnoid hemorrhage induced by cisternal injection of fresh arterial blood in rodents, electrophysiological recordings did not detect a single spreading depolarization for up to 72 h after subarachnoid hemorrhage. Cortical susceptibility to spreading depolarization, measured by direct electrical stimulation or topical KCl application, was suppressed after subarachnoid hemorrhage. Focal cerebral ischemia experimentally induced after subarachnoid hemorrhage revealed a biphasic change in the propensity to develop peri-infarct spreading depolarizations. Frequency of peri-infarct spreading depolarizations decreased at 12 h, increased at 72 h and normalized at 7 days after subarachnoid hemorrhage compared with sham controls. However, ischemic tissue and neurological outcomes were significantly worse after subarachnoid hemorrhage even when peri-infarct spreading depolarization frequency was reduced. Laser speckle flowmetry implicated cerebrovascular hemodynamic mechanisms worsening the outcome. Altogether, our data suggest that cerebral ischemia is required for spreading depolarizations to be triggered after subarachnoid hemorrhage, which then creates a vicious cycle leading to the delayed cerebral ischemia syndrome.

scholarly journals Spontaneous subarachnoid hemorrhage of unknown origin: hospital course and long-term clinical and angiographic follow-up

2015 ◽  
Vol 122 (3) ◽  
pp. 663-670 ◽  
Author(s):  
Ali M. Elhadi ◽  
Joseph M. Zabramski ◽  
Kaith K. Almefty ◽  
George A. C. Mendes ◽  
Peter Nakaji ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
External Ventricular Drain ◽  
Delayed Cerebral Ischemia ◽  
Unknown Origin ◽  
Unknown Etiology ◽  
Neurological Outcomes ◽  
Spontaneous Subarachnoid Hemorrhage

OBJECT Hemorrhagic origin is unidentifiable in 10%–20% of patients presenting with spontaneous subarachnoid hemorrhage (SAH). While the patients in such cases do well clinically, there is a lack of long-term angiographic followup. The authors of the present study evaluated the long-term clinical and angiographic follow-up of a patient cohort with SAH of unknown origin that had been enrolled in the Barrow Ruptured Aneurysm Trial (BRAT). METHODS The BRAT database was searched for patients with SAH of unknown origin despite having undergone two or more angiographic studies as well as MRI of the brain and cervical spine. Follow-up was available at 6 months and 1 and 3 years after treatment. Analysis included demographic details, clinical outcome (Glasgow Outcome Scale, modified Rankin Scale [mRS]), and repeat vascular imaging. RESULTS Subarachnoid hemorrhage of unknown etiology was identified in 57 (11.9%) of the 472 patients enrolled in the BRAT study between March 2003 and January 2007. The mean age for this group was 51 years, and 40 members (70%) of the group were female. Sixteen of 56 patients (28.6%) required placement of an external ventricular drain for hydrocephalus, and 4 of these subsequently required a ventriculoperitoneal shunt. Delayed cerebral ischemia occurred in 4 patients (7%), leading to stroke in one of them. There were no rebleeding events. Eleven patients were lost to followup, and one patient died of unrelated causes. At the 3-year follow-up, 4 (9.1%) of 44 patients had a poor outcome (mRS > 2), and neurovascular imaging, which was available in 33 patients, was negative. CONCLUSIONS Hydrocephalus and delayed cerebral ischemia, while infrequent, do occur in SAH of unknown origin. Long-term neurological outcomes are generally good. A thorough evaluation to rule out an etiology of hemorrhage is necessary; however, imaging beyond 6 weeks from ictus has little utility, and rebleeding is unexpected.

scholarly journals Cortical Spreading Ischemia in the Absence of Proximal Vasospasm after Aneurysmal Subarachnoid Hemorrhage: Evidence for a Dual Mechanism of Delayed Cerebral Ischemia

2011 ◽  
Vol 32 (2) ◽  
pp. 201-202 ◽  
Author(s):  
Anthony J Strong ◽  
R Loch Macdonald
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Preliminary Evidence ◽  
Circle Of Willis ◽  
Cerebral Microcirculation ◽  
Spreading Depolarization ◽  
Abnormal Response ◽  
Dual Mechanism

There are longstanding inconsistencies in the evidence thought to link vasospasm in the major branches of the Circle of Willis with delayed cerebral ischemia and poor outcome from aneurysmal subarachnoid hemorrhage (aSAH). The demonstrations, first in the laboratory, and more recently in patients with aSAH, of cortical spreading ischemia based on an abnormal response of the cerebral microcirculation to spreading depolarization offer an additional possible mechanism for delayed ischemia. That such events can occur in the substantial absence of proximal vasospasm is compatible with this concept, but the preliminary evidence needs support from more extensive studies.

Spreading depolarization-modulating drugs and delayed cerebral ischemia after subarachnoid hemorrhage: A hypothesis-generating retrospective clinical study

2016 ◽  
Vol 366 ◽  
pp. 224-228 ◽  
Author(s):  
Arend M. Hamming ◽  
Inge A. Mulder ◽  
Celine S. Gathier ◽  
Walter M. van den Bergh ◽  
Jan Willem Dankbaar ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Clinical Study ◽  
Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Spreading Depolarization ◽  
Retrospective Clinical Study

scholarly journals Role of SIRT1 in Isoflurane Conditioning-Induced Neurovascular Protection against Delayed Cerebral Ischemia Secondary to Subarachnoid Hemorrhage

2021 ◽  
Vol 22 (8) ◽  
pp. 4291
Author(s):  
Meizi Liu ◽  
Keshav Jayaraman ◽  
Tusar Giri ◽  
Gregory J. Zipfel ◽  
Umeshkumar Athiraman
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Mrna Expression ◽  
Delayed Cerebral Ischemia ◽  
Activity Levels ◽  
Neurological Outcomes ◽  
Neurovascular Protection ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

We recently reported that isoflurane conditioning provided multifaceted protection against subarachnoid hemorrhage (SAH)-induced delayed cerebral ischemia (DCI), and this protection was through the upregulation of endothelial nitric oxide synthase (eNOS). SIRT1, an NAD-dependent deacetylase, was shown to be one of the critical regulators of eNOS. The aim of our current study is to examine the role of SIRT1 in isoflurane conditioning-induced neurovascular protection against SAH-induced DCI. Mice were divided into four groups: sham, SAH, or SAH with isoflurane conditioning (with and without EX-527). Experimental SAH via endovascular perforation was performed. Anesthetic conditioning was performed with isoflurane 2% for 1 h, 1 h after SAH. EX-527, a selective SIRT1 inhibitor, 10 mg/kg was injected intraperitoneally immediately after SAH in the EX-527 group. SIRT1 mRNA expression and activity levels were measured. Vasospasm, microvessel thrombosis, and neurological outcome were assessed. SIRT1 mRNA expression was downregulated, and no difference in SIRT1 activity was noted after isoflurane exposure. Isoflurane conditioning with and without EX-527 attenuated vasospasm, microvessel thrombosis and improved neurological outcomes. Our data validate our previous findings that isoflurane conditioning provides strong protection against both the macro and micro vascular deficits induced by SAH, but this protection is likely not mediated through the SIRT1 pathway.

Abstract TMP102: Do Statins Decrease Mortality and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage? - Results from a Meta-Analysis

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Prasanna Sengodan ◽  
Pushkal Jadaun ◽  
Gaurav Kistangari
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Odds Ratio ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Meta Analysis ◽  
Delayed Cerebral Ischemia ◽  
Final Analysis ◽  
Forest Plot ◽  
Neurological Outcomes ◽  
Endothelial Nitric Oxide

Background: Aneurysmal subarachnoid hemorrhage (aSAH) induced cerebral vasospasm and delayed cerebral ischemia (DCI) are the major causes of morbidity and mortality in patients with aSAH. Recently, there has been growing interest in the use of statins, which raises cerebral endothelial nitric oxide synthase expression, improves endothelial function, increases cerebral blood flow and has been shown to protect against ischemia. However, the effect of statins use for patients with aSAH remain controversial with mixed results, with a latest meta-analysis demonstrating that statins have a potential benefit with regards to mortality and DCI. Methods: All randomized, placebo-controlled trials studying the effect of statins on vasospasm, DCI, poor neurological outcomes and death in aSAH were included. Search was done primarily using Medline (PubMed), where a total of 140 studies were identified using the search terms ‘statins’ and ‘subarachnoid hemorrhage’. The search was then narrowed down to 47 items, from which 7 studies were included for the final analysis. Statistical analysis was performed using the comprehensive meta-analysis software RevMan version 5.3 to obtain the odds ratio (risk ratio) estimates and also the forest plot comparisons. Results: In 7 studies, a total of 1052 patients were analyzed, 515 in the ‘statins’ group and 537 in the ‘placebo’ group were compared. There were no statistically significant differences between the two groups with regards to vasospasm observed with transcranial doppler (Odds ratio, 0.69 [95% CI, 0.68to 1.24]), poor neurological outcomes ( OR 0.97, [95% CI, 0.74-1.27]), and death (OR 0.74 [95% CI, 0.49-1.12])(Fig.4). A trend towards decreased risk of DCI was seen with the use of statins (OR, 0.79 [95% CI, 0.57-1.09) (Figures 1-4). The mean follow up was about 6 months. Conclusion: Statins have no benefit in terms of mortality, cerebral ischemia, DCI or poor neurological outcomes when compared to placebo in patients with aSAH. The current study does not support the routine use of statins for all patients with aSAH.

scholarly journals Association of Different Transcranial Doppler-derived Indices of Cerebrovascular Dynamics With Delayed Cerebral Ischemia in Patients Suffering From Subarachnoid Hemorrhage: A Retrospective Study

2020 ◽  
Author(s):  
Vasilios Papaioannou ◽  
Karol Budohoski ◽  
Michal Placek ◽  
Zofia Czosnyka ◽  
Peter Smielewski ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Transcranial Doppler ◽  
Cerebral Blood Flow Velocity ◽  
Delayed Cerebral Ischemia ◽  
Area Under The Curve ◽  
Arterial Blood ◽  
Potential Association ◽  
Temporal And Spatial ◽  
The Relationship

Abstract Background Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial doppler-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia.MethodsA retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in 2 groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) and arterial blood pressure was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Results In the whole population (N=32), magnitude of SWs of ipsilateral CBFV was increased during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/sec, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (p < 0.001) and were strongly predictive of DCI, with area under the curve = 0.745, p = 0.009. VS caused shortening of tau (ipsilateral to spasm: 0.17 ± 0.08 vs before: 0.25 ± 0.17 sec, p = 0.04) and interhemispheric asymmetry with lower values on ipsilateral side (p < 0.01). In patients with DCI (N=19), Mxa was increased during VS (ipsilateral to spasm: 0.36 ± 0.18 vs before: 0.26 ± 0.23, p = 0.04). ConclusionsIn the whole group of patients, VS was associated with increased CBFV SWs in both temporal and spatial assessments. Greater SWs before VS in DCI group, were strongly predictive of DCI.

Abstract T P355: Dobutamine versus Mirlinone for Intensive Hemodynamic Augmentation to Relieve Clinical Delayed Cerebral Ischemia after Subarachnoid Hemorrhage

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Tatsushi Mutoh ◽  
Tatsuya Ishikawa ◽  
Ken Kazumata ◽  
Keigo Matsumoto ◽  
Yasuyuki Taki ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Near Infrared ◽  
Cerebral Oxygenation ◽  
Focal Cerebral Ischemia ◽  
Delayed Cerebral Ischemia ◽  
Clinical Deterioration ◽  
Dose Increment ◽  
Hemodynamic Augmentation ◽  
Hyperdynamic Therapy

Intensive hemodynamic augmentation by increasing cardiac output (CO) is a valuable method of elevating cerebral blood flow and oxygenation in the dysautoregulated vascular territories after subarachnoid hemorrhage (SAH). We prospectively assessed the effect of hyperdynamic therapy with dobutamine (DOB) or milrinone (MIL) on regional cerebral oxygenation (rSO 2 ) for reversing clinical deterioration induced by delayed cerebral ischemia, using an integrative monitoring with uncalibrated pulse contour CO analysis and multi-channel near-infrared spectroscopy. One-hundred ten SAH patients diagnosed to have clinical deterioration due to delayed cerebral ischemia were assigned to receive hemodynamic augmentation with DOB or MIL (n=56 per each group). For hyperdynamic therapy, each inotrope was initiated at low dose (DOB: 3μg/kg/min; MIL 0.15μg/kg/min) and then increased in each dose increment until resolution of the symptoms unless any adverse effects occur during the therapy, based on our predefined hemodynamic regimen to induce similar dose-related increase in CO. Real-time CO and rSO 2 changes in conjunction with the assessment of neurological improvements were compared. A total of 425 dose increment challenges (DOB, n=197; MIL, n=228) were performed. In spasm-affected territories, decreased and/or fluctuating rSO 2 was detected compared with recordings in other brain region. Patients who exhibited rapid elevation of CO by each challenge had subsequent uptake and stabilization of rSO 2 . The responses (total number and degree of neurological improvements) were more significant in patients treated with DOB than those treated with MIL ( P < 0.05), although tachycardia that may affect stroke volume depression during the DOB therapy was more evident (DOB 28% vs. MIL 9%). Area under the ROC curve to predict rSO 2 elevation or neurological improvement for both drug groups were significant ( P < 0.0001) and the values were significantly greater in DOB than in MIL ( P < 0.05). In conclusion, DOB can provide more effective hemodynamic augmentation in relieving focal cerebral ischemia in patients after SAH. MIL is also effective in the hyperdynamic therapy but may be used as a second line in a patient subgroup when DOB was contraindicated.

Sign in / Sign up

Export Citation Format

Share Document