A Rabbit Cisterna Magna Double-Injection Subarachnoid Hemorrhage Model

Author(s):  
Yuichiro Kikkawa
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.


Author(s):  
Martin Pedard ◽  
Mohamad El Amki ◽  
Antoine Lefevre-Scelles ◽  
Vincent Compère ◽  
Hélène Castel

2015 ◽  
Vol 8 (7) ◽  
pp. 728-731 ◽  
Author(s):  
Alex M Mortimer ◽  
Auke PA Appelman ◽  
Shelley A Renowden

BackgroundPerimesencephalic subarachnoid hemorrhage (PMSAH) is only rarely associated with a ruptured cerebral aneurysm and CT angiography (CTA) has very good sensitivity and specificity for aneurysm detection. The necessity for invasive imaging with digital subtraction angiography (DSA) is therefore debatable. We chose to assess the negative predictive value (NPV) of CTA in a series of patients with PMSAH treated at our institution over a 9-year period.MethodsWe retrospectively assessed the diagnostic yield of DSA after initial negative CTA in patients with a PMSAH pattern defined as blood centered anterior to the midbrain and/or pons within the pre-pontine or interpeduncular cistern with possible quadrigeminal or ambient cistern extension; possible extension into the basal parts of the sylvian fissures but not the lateral sylvian fissures; possible extension to the cisterna magna but not centered on the cisterna magna; and possible extension into the fourth ventricle and occipital horns of the lateral ventricles.ResultsUsing this definition of PMSAH, of 72 patients, one patient showed a potentially significant finding on DSA that was not demonstrated on initial CTA (NPV 98.61% (95% CI 92.47% to 99.77%)). However, when cisterna magna extension was excluded from the definition of PMSAH, no false negative CTAs in 56 patients were encountered (NPV 100% (95% CI 93.56% to 100.00%)).ConclusionsThe NPV of normal CTA for an arterial abnormality in patients with PMSAH is high and our results therefore question the role of invasive imaging. The findings also suggest that a prospective study designed to clarify the necessity of performing DSA in this population would be feasible.


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.


2004 ◽  
Vol 101 (1) ◽  
pp. 99-103 ◽  
Author(s):  
Gustavo Pradilla ◽  
Paul P. Wang ◽  
Federico G. Legnani ◽  
James L. Frazier ◽  
Rafael J. Tamargo

Object. Implantation of controlled-release polymers into the subarachnoid space to deliver drugs for treatment of vasospasm after subarachnoid hemorrhage (SAH) is currently of interest. Among the issues regarding local delivery of drugs in the subarachnoid space, however, are the extent of diffusion and the rate of release of the loaded agents. In this study Evans blue dye (EBD) was loaded into controlled-release polymers and its pharmacokinetic properties were determined in vitro and in vivo by using a rabbit model of SAH. Methods. Ethylene—vinyl acetate copolymer (EVAc) was loaded 40% (w:w) with EBD and its pharmacokinetics were spectrophotometrically determined in vitro by examining three EBD—EVAc polymers. Additional polymers were implanted either into the frontal lobe or into the cisterna magna of 16 New Zealand White rabbits. Subarachnoid hemorrhage was induced in eight of the animals by an injection of 1.5 ml of arterial blood into the cisterna magna. The animals were killed 3 or 14 days postoperatively, their brains and spinal cords were harvested, and samples of each were placed in formamide for dye extraction and quantification. Specimens were examined macroscopically and the concentrations of EBD were determined with the aid of a spectrophotometer. The EBD—EVAc polymers continuously released EBD over a 133-day period. The controlled release of the dye into the subarachnoid space in either location resulted in staining of the entire central nervous system (CNS) in rabbits when the polymers were placed either on the frontal lobe or in the cisterna magna. The EBD diffusion covered a distance of at least 40 cm. The presence of blood in the subarachnoid space did not interfere with the diffusion. Conclusions. In this study the authors define the rate and extent of diffusion of EBD from controlled-release polymers placed in the subarachnoid space under conditions of SAH. Evans blue dye diffused through the entire rabbit CNS, covering a distance greater than that of the longest dimension of the hemicircumference of the subarachnoid space around the human brain. The pharmacokinetic properties of EBD—EVAc polymers are comparable to those of antivasospasm agents that are successfully used in animal models of SAH.


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