scholarly journals Vascular Reactivity to Hypercapnia Is Impaired in the Cerebral and Retinal Vasculature in the Acute Phase After Experimental Subarachnoid Hemorrhage

2022 ◽  
Vol 12 ◽  
Author(s):  
Laura Warner ◽  
Annika Bach-Hagemann ◽  
Walid Albanna ◽  
Hans Clusmann ◽  
Gerrit A. Schubert ◽  
...  

Objective: Impaired cerebral blood flow (CBF) regulation, such as reduced reactivity to hypercapnia, contributes to the pathophysiology after aneurysmal subarachnoid hemorrhage (SAH), but temporal dynamics in the acute phase are unknown. Featuring comparable molecular regulation mechanisms, the retinal vessels participate in chronic and subacute stroke- and SAH-associated vessel alterations in patients and can be studied non-invasively. This study is aimed to characterize the temporal course of the cerebral and retinal vascular reactivity to hypercapnia in the acute phase after experimental SAH and compare the potential degree of impairment.Methods: Subarachnoid hemorrhage was induced by injecting 0.5 ml of heparinized autologous blood into the cisterna magna of male Wistar rats using two anesthesia protocols [isoflurane/fentanyl n = 25 (Sham + SAH): Iso—Group, ketamine/xylazine n = 32 (Sham + SAH): K/X—Group]. CBF (laser speckle contrast analysis) and physiological parameters were measured continuously for 6 h. At six predefined time points, hypercapnia was induced by hypoventilation controlled via blood gas analysis, and retinal vessel diameter (RVD) was determined non-invasively.Results: Cerebral reactivity and retinal reactivity in Sham groups were stable with only a slight attenuation after 2 h in RVD of the K/X—Group. In the SAH Iso—Group, cerebral and retinal CO2 reactivity compared to baseline was immediately impaired starting at 30 min after SAH (CBF p = 0.0090, RVD p = 0.0135) and lasting up to 4 h (p = 0.0136, resp. p = 0.0263). Similarly, in the K/X—Group, cerebral CO2 reactivity was disturbed early after SAH (30 min, p = 0.003) albeit showing a recovery to baseline after 2 h while retinal CO2 reactivity was impaired over the whole observation period (360 min, p = 0.0001) in the K/X—Group. After normalization to baseline, both vascular beds showed a parallel behavior regarding the temporal course and extent of impairment.Conclusion: This study provides a detailed temporal analysis of impaired cerebral vascular CO2 reactivity starting immediately after SAH and lasting up to 6 h. Importantly, the retinal vessels participate in these acute changes underscoring the promising role of the retina as a potential non-invasive screening tool after SAH. Further studies will be required to determine the correlation with functional outcomes.

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Jorge A Roa ◽  
Deepon Sarkar ◽  
Mario Zanaty ◽  
David Hasan ◽  
Edgar Samaniego ◽  
...  

Introduction: Cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) are frequently observed after aneurysmal subarachnoid hemorrhage (aSAH) and contribute to neurocognitive decline and worse outcomes. We hypothesize that aSAH initiates a cascade of neuroinflammatory events which contributes to the development of DCI. Methods: Patients who presented with aSAH requiring external ventricular drainage (EVD) for concomitant hydrocephalus were prospectively enrolled. Cerebrospinal fluid (CSF) samples were collected at different time-points relative to index aSAH injury: acute (days 0-1); pre-vasospasm (days 2-5); vasospasm peak (days 6-9) and post-vasospasm (days 10+). Presence and severity of CVS were assessed using CTA/CTP scans and clinical exam. VEGF and MMP9 (immune affectors) protein levels in the CSF were quantified using ELISA. Mobilization of the immune system was characterized by quantification of innate and adaptive immune cells in the CSF using flow cytometry. Production of inflammatory effector proteins was evaluated using intracellular cytokine staining. Results: Of 13 patients analyzed, 6 (46.2%) experienced CVS. Levels of VEGF and MMP9 were consistently higher in aSAH patients who developed CVS, with the highest difference occurring at the acute phase. Similarly, cellularity analysis revealed elevated counts of monocytes (CD11b + ) in the CSF during the acute phase, with progressive decline at later phases. Microglia (CD45 dim CD11b + ) cells were found to be significantly increased at the post-vasospasm phase. A higher percentage of IFN-γ production cytotoxic T helper cells were found at the acute phase, while the later time points revealed an elevated leveled of CD45RA - CD27 + cytotoxic T cells. Conclusion: Our preliminary data shows an active production of proteins with known immunological functions, mobilization of innate cells, production of inflammatory mediators by adaptive immune cells and altered differentiation status. Our overall goal is to determine if there are potential targets of immunomodulatory therapies which can be used to prevent or treat vasospasms and its related deleterious outcomes.


Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Fumiaki Oka ◽  
Yahya B Atalay ◽  
Tao Qin ◽  
Cenk Ayata

Background: Majority of aneurysmal subarachnoid hemorrhage (SAH) survivors develop cognitive dysfunction. To better understand the underlying mechanisms and develop treatments, predictive animal models are required. We carried out a detailed physiological and cognitive characterization of pre-chiasmatic cistern (PC) and cisterna magna (CM) SAH models in mice. Methods: SAH was induced by arterial blood injection into the PC (40 μl) or CM (60 μl) in C57BL6/J mice (male, 25g). Controls received normal saline. Cerebral blood flow (CBF) was imaged using laser speckle flowmetry during and for 60 min after SAH. Intracranial pressure (ICP) and blood pressure (BP) were monitored to calculate cerebral perfusion pressure (CPP). Neurological and cognitive function was assessed 3 weeks after the injection, using pole, novel object recognition, Y maze and Morris water maze tests. Results: Mortality was 10% after PC and 4% after CM SAH. In both groups, CPP decreased from about 65 mmHg to less than 10 mmHg immediately after the injection, and recovered to 40 mmHg within 10 min after PC (n=8) and 7 min after CM (n=8) SAH (Fig A). In both groups, CBF was severely reduced to ~20% of baseline in both hemispheres immediately after SAH. CBF recovered to >40% within 5 min after PC and 2 min after CM SAH (Fig A). In saline controls (n=5 in PC and CM each), CPP and CBF changes were much milder and shorter-lasting. Compared with controls (n=12), PC SAH mice (n=12) performed significantly worse in a subset of sensorimotor and cognitive tests for up to 3 weeks (Fig B). CM SAH did not significantly impact neurological function. Conclusions: Pre-chiasmatic cistern but not cisterna magna SAH model reproduces cognitive dysfunction observed in patients with low mortality and high reproducibility in mice.


2019 ◽  
Vol 124 (4) ◽  
pp. 254-259 ◽  
Author(s):  
Christoffer Nyberg ◽  
Elisabeth Ronne Engström ◽  
Lars Hillered ◽  
Torbjörn Karlsson

2020 ◽  
Vol 162 (12) ◽  
pp. 3107-3116
Author(s):  
Elin Western ◽  
Angelika Sorteberg ◽  
Cathrine Brunborg ◽  
Tonje Haug Nordenmark

Abstract Background Fatigue is a common and disabling sequel after aneurysmal subarachnoid hemorrhage (aSAH). At present, prevalence estimates of post-aSAH fatigue in the chronic phase are scarce and vary greatly. Factors from the acute phase of aSAH have hitherto barely been associated with post-aSAH fatigue in the chronic phase. Methods Prospective study assessing prevalence of fatigue using the Fatigue Severity Scale (FSS) in patients who were living independently 1 to 7 years after aSAH. We compared demographic, medical, and radiological variables from the acute phase of aSAH between patients with and without fatigue (FSS ≥ 4 versus < 4) and searched for predictors of fatigue among these variables applying univariable and multivariable regression analyses. Results Of 726 patients treated for aSAH in the period between January 2012 and December 2017, 356 patients completed the assessment. The mean FSS score was 4.7 ± 1.7, and fatigue was present in 69.7%. The frequency of patients with fatigue did not decline significantly over time. Univariable analysis identified nicotine use, loss of consciousness at ictus (LOCi), rebleed prior to aneurysm repair, reduced consciousness to Glasgow Coma Scale (GCS) < 14, large amounts of subarachnoid blood, the presence of acute hydrocephalus, and severe vasospasm as factors that were significantly associated with fatigue. In multivariable analysis, nicotine use, reduced GCS, and severe vasospasm were independent predictors that all more than doubled the risk to develop post-aSAH fatigue. Conclusions Fatigue is a frequent sequel persisting several years after aSAH. Nicotine use, reduced consciousness at admission, and severe vasospasm are independent predictors of fatigue from the acute phase of aSAH. We propose inflammatory cytokines causing dopamine imbalance to be a common denominator for post-aSAH fatigue and the presently identified predictors.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Koichi Uramaru ◽  
Yuichiro Kikkawa ◽  
Hiroki Sato ◽  
Taro Yanagawa ◽  
Kaima Suzuki ◽  
...  

Objectives: The characteristics of serum catecholamine concentration at the hyper-acute phase of aneurysmal subarachnoid hemorrhage (SAH) and its relationship between patient outcome and delayed vasospasm were investigated. Methods: Patients with aneurysmal SAH (170) were prospectively studied between August 2008 and June 2011. Baseline demographic data and physiological parameters, including plasma concentrations of adrenaline (AD), noradrenaline (NA) and dopamine (DP) were evaluated for all patients. Results: On admission, plasma AD, NA and DP levels were significantly higher in patients with a poor clinical grade on admission (Hunt & Kosnik: IV-V), compared to those with a good clinical grade on admission (Hunt & Kosnik: I-III). AD showed a markedly high concentration immediately after the onset of SAH and then rapidly decreased. NA levels peaked within 6 hours after onset, then significantly decreased. The increase of DP with time was not significant, but showed a similar trend to that of NA. The level of each catecholamine showed significant mutual correlation. Multivariate analyses demonstrated age, poor clinical grade, plasma AD and NA levels were predictors of poor patient outcome, and.poor clinical grade, Fisher scale and plasma AD level were predictors of the development of delayed vasospasm. Conclusions: The present findings suggest that sympathetic activation in patients in the acute phase of SAH reflects the severity of SAH, and is closely related to the development of delayed vasospasm, leading to the subsequent immune response and inflammatory reactions. Strategies for suppressing catecholamine at the hyperacute phase may contribute to vasospasm prevention and improve patient outcome.


2018 ◽  
Vol 55 (8) ◽  
pp. 6841-6849 ◽  
Author(s):  
Yoshinari Nakatsuka ◽  
◽  
Masato Shiba ◽  
Hirofumi Nishikawa ◽  
Mio Terashima ◽  
...  

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