Rat Cisterna Magna Double-Injection Model of Subarachnoid Hemorrhage – Background, Advantages/Limitations, Technical Considerations, Modifications, and Outcome Measures

Author(s):  
Erdem Güresir ◽  
Patrick Schuss ◽  
Valeri Borger ◽  
Hartmut Vatter
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.


1990 ◽  
Vol 72 (5) ◽  
pp. 792-797 ◽  
Author(s):  
Kazuhiko Nozaki ◽  
Shinichiro Okamoto ◽  
Yoshihiko Uemura ◽  
Haruhiko Kikuchi ◽  
Noboru Mizuno

✓ The vascular relaxation effects of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) on the dog basilar artery after experimentally produced subarachnoid hemorrhage (SAH) were examined in vitro by an isometric tension recording method. Both CGRP and VIP induced dose-dependent relaxations in ring segments of the intact basilar artery of control dogs. The vasorelaxant action of CGRP was more potent than that of VIP. The single-injection model of SAH was produced by injection of fresh autologous arterial blood ( 1 ml/kg body weight) into the cisterna magna on Day 0 of the post-SAH period, and the double-injection model was produced by two injections of blood (0.5 ml/kg each) on Days 0 and 2. Narrowing of the basilar arteries on vertebral angiograms was most prominent on Day 3 or 7 in the single- or double-injection model, respectively. Relaxation of the basilar artery induced by CGRP and VIP was to some extent decreased on Days 3 and 7 of the post-SAH period in the single-injection model, and on Days 7 and 14 in the double-injection model. However, the vasorelaxant effects of CGRP and VIP were significantly enhanced on Day 14 of the post-SAH period in the single-injection model, and on Days 28 and 42 in the double-injection model. Subsequently, these effects returned to control levels by Days 28 or 63 in the single- or double-injection model, respectively.


1989 ◽  
Vol 71 (4) ◽  
pp. 558-564 ◽  
Author(s):  
Kazuhiko Nozaki ◽  
Yoshihiko Uemura ◽  
Shinichiro Okamoto ◽  
Haruhiko Kikuchi ◽  
Noboru Mizuno

✓ This study examines the relaxant effect of calcitonin gene-related peptide (CGRP), a 37-amino acid peptide with a potent vasodilator action, on cerebral arterial spasm after subarachnoid hemorrhage (SAH). The spasm was induced by injecting autologous arterial blood percutaneously into the cisterna magna in adult mongrel dogs. The single-injection model of SAH was produced by injection of 1.0 ml/kg body weight of blood (on Day 0), and the double-injection model involved two successive injections of 0.5 ml/kg body weight of blood made 48 hours apart (on Day 0 and Day 2). On vertebral angiograms, arterial narrowing of the major cerebral arteries was most prominent on Day 3 after SAH in the single-injection model and on Day 7 in the double-injection model. When 10−10 mol/kg of CGRP was administered intracisternally in the single-injection model on Day 3, the diameter of the spastic cerebral arteries, as determined by angiography, recovered to normal. After intracisternal administration of 10−11 to 2 × 10−10 mol/kg of CGRP on Day 7 in double-injection models, spastic cerebral arteries dilated in a dose-dependent manner. The dilatory effect of CGRP continued for a few hours after administration. The results suggest that CGRP injected intracisternally may reverse cerebral arterial spasm after SAH.


2006 ◽  
Vol 18 (1) ◽  
pp. 18-23 ◽  
Author(s):  
XiaoDong Ma ◽  
Rikke Bay-Hansen ◽  
John Hauerberg ◽  
Gitte Moos Knudsen ◽  
Niels Vidiendal Olsen ◽  
...  

2012 ◽  
Vol 34 (2) ◽  
pp. 292-298 ◽  
Author(s):  
P.C. Sanelli ◽  
N. Anumula ◽  
C.E. Johnson ◽  
J.P. Comunale ◽  
A.J. Tsiouris ◽  
...  

Author(s):  
Umit Eroglu ◽  
Murat Büyüktepe ◽  
Murat Zaimoğlu ◽  
Gokmen Kahilogullari ◽  
Hasan Caglar Ugur ◽  
...  

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Daniel Haenggi ◽  
Nima Etminan ◽  
Hans Jakob Steiger ◽  
R. Loch Macdonald ◽  
Stephan A Mayer ◽  
...  

Few treatments for aneurysmal subarachnoid hemorrhage (aSAH) have been effective in randomized clinical studies. One reason may be that the outcome measures used are not sensitive enough to detect efficacy of treatments in this disease. This hypothesis was examined by comparing 6 outcome measures for 72 patients with aSAH. Patients with aSAH who were World Federation of Neurological Surgeons grades 2 to 4 with an external ventricular drain inserted as part of standard of care were entered in a Phase 1/2a multicenter, controlled, randomized, open-label, dose escalation study to determine the maximum tolerated dose and safety and tolerability of a sustained release formulation of nimodipine (EG-1962, NEWTON study) in patients with aSAH. Clinical outcome was assessed at 90 days after aSAH using the extended Glasgow outcome scale (eGOS), modified Rankin scale (mRS), Montreal cognitive assessment (MoCA), telephone interview of cognitive status (TICS), NIHSS and Barthel index. The relationship between each outcome measure and the eGOS was plotted on arithmetic graphs (Figure). The eGOS and mRS gave very similar results. More detailed cognitive assessments (MoCA, TICS) were more exponential in shape with more variability. The NIHSS and Barthel had outcomes clustered towards the highest ends of the scales with distributions that did not discriminate as much as the eGOS or mRS. The MoCA and TICS gave similar results. It was concluded that the eGOS or mRS produce a similar and varying range of outcomes after aSAH, whereas cognitive assessments like the MoCA and TICS and scales designed for ischemic stroke like the NIHSS and BI are less discriminatory of outcomes after aSAH.


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