Cerebral vasospasm in a double-injection model in rabbit

Acta Neurochirurgica, 1991

Although the pathophysiology of chronic cerebral vasospasm following subarachnoid haemorrhage (SAH) is still unclear, it is certain that the amount of subarachnoid blood is predictive of the severity of cerebral vasospasm. Accordingly, massive subarachnoid haemorrhage (> 0.5 ml) was induced in adult rats via direct injection into the cisterna magna. Compared to other previously published models of experimental SAH in rats a much larger amount of blood was injected. The basilar artery was exposed 72 hours post subarachnoid haemorrhage and photographed under controlled conditions. The diameter of the artery was assessed by an image analyzer. A 50% reduction in diameter was found in 25 rats subjected to SAH as compared to 9 control rats and 4 rats with intracisternal saline injection. We conclude that when massive subarachnoid haemorrhage is induced, and direct measurements of the basilar artery are made, the rat can be used as a reliable model for investigation of SAH induced arterial vasospasm.

Stroke, 1988

Cerebral blood flow was measured by a [ l4 C]butanol indicator fractionation technique in rats subjected to subarachnoid hemorrhage, in control rats, and in rats given injections of buffered saline into the subarachnoid space (sham hemorrhage). Cerebral blood flow was significantly decreased in both the subarachnoid hemorrhage and sham hemorrhage rats 3 hours after injection. However, blood flow returned to control levels by 24 hours, and measurement for 14 days after subarachnoid hemorrhage failed to show any delayed decrease in cerebral blood flow. Electron microscopic studies of basilar arteries from rats subjected to subarachnoid hemorrhage 72 hours before killing failed to show any of the morphologic changes that have been associated with vasospasm in humans or in higher animal models. Our studies indicate that the rat model of subarachnoid hemorrhage has limited applicability to the study of subarachnoid hemorrhage following ruptured cerebral aneurysms in humans. However, although rats are not a perfect model of this clinical condition, some pathophysiologic changes similar to those observed in human subarachnoid hemorrhage have been demonstrated in this model and deserve further investigation.

Surgical Neurology International, 2011

Background: Double-injection models of subarachnoid hemorrhage (SAH) in rats are the most effective in producing vasospasm, delayed neurological deficits and infarctions. However, they require two large surgeries to expose the femoral artery and the atlanto-occipital membrane. We have developed a minimally-invasive modification that prevents confounding effects of surgical procedures, leakage of blood from the subarachnoid space and minimizes risk of infection. Methods: Rats are anesthetized and the ventral tail artery is exposed through a small (5 mm), midline incision, 0.2 mL of blood is taken from the artery and gentle pressure is applied for hemostasis. The rat is flipped prone, and with the head flexed to 90 degrees in a stereotactic frame, a 27G angiocath is advanced in a vertical trajectory, level with the external auditory canals. Upon puncturing the atlanto-occipital membrane, the needle is slowly advanced and observed for cerebrospinal fluid (CSF). A syringe withdraws 0.1 mL of CSF and the blood is injected into the subarachnoid space. The procedure is repeated 24 hours later by reopening the tail incision. At 8 days, the rats are euthanized and their brains harvested, sectioned, and incubated with triphenyltetrazolium chloride (TTC). Results: Rats develop neurological deficits consistent with vasospasm and infarction as previously described in double-injection models. Cortical and deep infarctions were demonstrated by TTC staining and on histopathology. Conclusions: A minimally invasive, double-injection rat model of SAH and vasospasm is feasible and produces neurological deficits and infarction. This model can be used to study neuroprotective treatments for vasospasm and delayed neurological deficits following SAH, reducing the confounding effects of surgical interventions.

Frontiers in molecular neuroscience, 2018

Non-traumatic subarachnoid hemorrhage (SAH) affects an estimated 30,000 people each year in the United States, with an overall mortality of ~30%. Most cases of SAH result from a ruptured intracranial aneurysm, require long hospital stays, and result in significant disability and high fatality. Early brain injury (EBI) and delayed cerebral vasospasm (CV) have been implicated as leading causes of morbidity and mortality in these patients, necessitating intense focus on developing preclinical animal models that replicate clinical SAH complete with delayed CV. Despite the variety of animal models currently available, translation of findings from rodent models to clinical trials has proven especially difficult. While the explanation for this lack of translation is unclear, possibilities include the lack of standardized practices and poor replication of human pathophysiology, such as delayed cerebral vasospasm and ischemia, in rodent models of SAH. In this review, we summarize the differe...

Brain Research, 2009

A model of subarachnoid hemorrhage (SAH) first described in rats where blood is injected into the prechiasmatic cistern was adapted to mice. The hypothesis was that such an anterior circulation SAH model would produce vasospasm of greater severity and longer duration than other mouse models. The goal was to create a mouse model that could then be used in transgenic and knockout animals in order to further knowledge of SAH and vasospasm. A needle was inserted stereotactically into the prechiasmatic cistern and 100 µl autologous arterial blood injected over seconds (n = 10). Effects were compared to injection of saline (n = 10) or to sham operation (n = 7). Monitoring of cerebral blood flow by laser Doppler showed a statistically similar decrease during injection in both groups. 7 days after SAH there was vasospasm of the middle and anterior cerebral arteries (51% reduction in MCA radius in SAH compared to saline-injected group, P < 0.009, Student's t-test). In order to determine if SAH in this model was associated with neuronal injury, brains were examined for TUNEL and fluoro-jade-positive cells. 60% of SAH but not saline-injected mice exhibited TUNEL-positive cells in the cerebral cortex and 30% of the SAH but no saline-injected mice had fluoro-jade positive cells in the cortex, hippocampus and dentate gyrus. The model is simple to perform and may be useful for investigating the pathophysiology of SAH.

Research and Publishing in Neurosurgery, 2002

There is no comprehensive and reliable model available in small animals that are suitable for the study of subarachnoid haemorrhage (SAH). In the study we reviewed the advantages and disadvantages of available SAH models in rats and presented our model. Experimental SAH was induced in a group of 350-450 g Sprague-Dawley rats. A 2 mm-diameter burr hole was drilled and, working under a microscope, haemorrhage was produced by transclival puncture of the basilar artery with a 20 mm thick piece of glass. The rats were assigned to either the experimental group (n: 7) or the control group (n: 7). Local cerebral blood flow (LCBF), intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were measured for 60 min after SAH, after which the rats were decapitated. Microscopic examinations were done on three di¤erent segments of the basilar artery. There was a significant and sharp drop in LCBF just after SAH was induced (56.17 G 12.80 mlLD/min/100 g and 13.57 G 5.85 mlLD/min/100 g for baseline and post-SAH, respectively; p < 0.001), the flow slowly increased by the end of the experiment but never recovered to pre-SAH values (43,63 G 7.6 mlLD/min/ 100 g, p < 0.05). ICP (baseline 7.33 G 0.8 mmHg) increased acutely to 70.6 G 9.2 mmHg, and also returned to normal levels by 60 min after SAH. CPP (baseline 75.1 G 4.9 mmHg) dropped accordingly (to 21.0 G 6.3 mmHg) and then increased, reaching 70.1 G 4.9 mmHg at 60 min after SAH. Examinations of the arteries revealed decreased inner luminal diameter and distortion of the elastica layer. We present an inexpensive and reliable model of SAH in the rat that allows single and multiple haemorrhages and to study the early and late course of pathological changes.

Acta Neurochirurgica, 1992

Haemodynamic instability is of great importance in clinical management of patients with subarachnoid haemorrhage (SAH). The significance of angiographicaUy demonstrable vasospasm for disturbances of cerebral blood flow (CBF) and cerebral autoregulation has not yet been clarified.

Neuroradiology, 2002

Turkish Neurosurgery, 2020

To compare the histological and angiographic measurements of the basilar artery in an experimental rabbit subarachnoid hemorrhage model. The basilar artery was measured using both histological and angiographic methods in experimental subarachnoid hemorrhage (SAH) and vasospasm rabbit models. New Zealand white rabbits were randomly categorized into two groups: control and SAH groups. The SAH group rabbits were operated on to create an experimental SAH. Both groups were examined angiographic and histological methods. On comparing the two methods, angiographic and histopathological measurements of the basilar artery were similar in the control group. However, in the SAH group, the difference between the angiographic and histopathological measurement methods was significant. Histopathological measurements of the basilar artery were lower than angiographic measurements, and the difference was statistically significant. In the angiographic method, although there was a marked decrease in basilar artery measurements in the SAH group, the differences between the groups was not statistically significant. However, in the histopathological method, measurement differences between the control and SAH groups were statistically significant. CONCLUSION: Histopathological measurements were shown to be more sensitive than angiographic methods in demonstrating cerebral vasopasm in experimental SAH rabbit models.

Neurosurgical review, 2017

Pathophysiological processes following subarachnoid hemorrhage (SAH) present survivors of the initial bleeding with a high risk of morbidity and mortality during the course of the disease. As angiographic vasospasm is strongly associated with delayed cerebral ischemia (DCI) and clinical outcome, clinical trials in the last few decades focused on prevention of these angiographic spasms. Despite all efforts, no new pharmacological agents have shown to improve patient outcome. As such, it has become clear that our understanding of the pathophysiology of SAH is incomplete and we need to reevaluate our concepts on the complex pathophysiological process following SAH. Angiographic vasospasm is probably important. However, a unifying theory for the pathophysiological changes following SAH has yet not been described. Some of these changes may be causally connected or present themselves as an epiphenomenon of an associated process. A causal connection between DCI and early brain injury (EBI)...