Abstract T P242: Cognitive Dysfunction in a Pre-chiasmatic Cistern Blood Injection Model of Aneurysmal Subarachnoid Hemorrhage In Mice

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.

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

2020 ◽  
Vol 190 ◽  
pp. 105639
Author(s):  
Arthur Hosmann ◽  
Sarah Klenk ◽  
Wei-te Wang ◽  
Johannes Koren ◽  
Samir Sljivic ◽  
...  

1994 ◽  
Vol 80 (5) ◽  
pp. 857-864 ◽  
Author(s):  
Joseph M. Darby ◽  
Howard Yonas ◽  
Elizabeth C. Marks ◽  
Susan Durham ◽  
Robert W. Snyder ◽  
...  

✓ The effects of dopamine-induced hypertension on local cerebral blood flow (CBF) were investigated in 13 patients suspected of suffering clinical vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The CBF was measured in multiple vascular territories using xenon-enhanced computerized tomography (CT) with and without dopamine-induced hypertension. A territorial local CBF of 25 ml/100 gm/min or less was used to define ischemia and was identified in nine of the 13 patients. Raising mean arterial blood pressure from 90 ± 11 mm Hg to 111 ± 13 mm Hg (p < 0.05) via dopamine administration increased territorial local CBF above the ischemic range in more than 90% of the uninfarcted territories identified on CT while decreasing local CBF in one-third of the nonischemic territories. Overall, the change in local CBF after dopamine-induced hypertension was correlated with resting local CBF at normotension and was unrelated to the change in blood pressure. Of the 13 patients initially suspected of suffering clinical vasospasm, only 54% had identifiable reversible ischemia. The authors conclude that dopamine-induced hypertension is associated with an increase in flow in patients with ischemia after SAH. However, flow changes associated with dopamine-induced hypertension may not be entirely dependent on changes in systemic blood pressure. The direct cerebrovascular effects of dopamine may have important, yet unpredictable, effects on CBF under clinical pathological conditions. Because there is a potential risk of dopamine-induced ischemia, treatment may be best guided by local CBF measurements.


Neurosurgery ◽  
1988 ◽  
Vol 22 (5) ◽  
pp. 822-826 ◽  
Author(s):  
Paul D. Dernbach ◽  
John R. Little ◽  
Stephen C. Jones ◽  
Zeyd Y. Ebrahim

Abstract Disruption of local cortical blood flow (CBF) autoregulation and CO2 reactivity, or vasoparalysis, has been documented in humans after aneurysmal subarachnoid hemorrhage (SAH). Generally, the degree of vasoparalysis is related to the patient's clinical grade. Using intraoperative measurement of local CBF, we evaluated pressure autoregulation and CO2 reactivity in patients after SAH. Fourteen patients with SAH and 10 patients with asymptomatic aneurysm underwent craniotomy for clipping of their aneurysms. During operation, local CBF was recorded with thermal conductivity probes placed on the middle frontal gyrus, 4 to 6 cm from the nearest point of retraction. Before retractor placement, CBF was measured with the PCO2 at 25 and 35 mm Hg and the mean arterial blood pressure (MABP) between 70 and 80 mm Hg. After aneurysm clipping, flows were again measured. With the PCO2 at 25 mm Hg, the MABP was raised from 65 to 85 mm Hg. The PCO2 was then allowed to rise to 35 mm Hg, after which the MABP was lowered from 85 to 65 mm Hg. Six patients underwent operation within the 1st week after SAH (Grade I, n = 3; Grade II, n = 3). The remainder (n = 8) were operated on 9 days to 3 months after SAH. After aneurysm clipping, significant CBF changes (P &lt; 0.001) with PCO2 alteration occurred in control patients and those operated on more than 7 days after SAH. There was no significant change in CBF in patients operated on within 7 days after SAH. Changes in CBF reactivity to alteration of MABP were significantly larger in early operation patients than in other groups (P &lt; 0.008). Pressure autoregulation and CO2 reactivity are significantly disturbed in good grade patients after early operation.


2008 ◽  
Vol 108 (3) ◽  
pp. 458-463 ◽  
Author(s):  
Janine Keuskamp ◽  
Raj Murali ◽  
Kuo H. Chao

Object Because oral calcium channel blockers appear to reduce the severity of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), interest in their application intraarterially has emerged for cases in which noninvasive means of alleviating vasospasm are unsuccessful. Studies to date have been limited to the administration of low intraarterial doses because of concerns about hemodynamic stability and changes in intracranial pressure. These doses, although effective in cases of milder vasospasm, were inadequate in severe cases. The authors present a series of 10 patients with cerebral vasospasm who underwent 12 procedures in which they received ≥ 20 mg of intraarterial verapamil per procedure. Methods A retrospective review was undertaken of all patients who underwent endovascular treatment for cerebral vasospasm due to aneurysmal SAH by the senior author between February 2005 and October 2006. Ten patients were identified who had undergone a total of 12 procedures during which ≥20 mg of intraarterial verapamil had been administered. From angiography reports, anesthesia records, and nursing records, we obtained pre- and postverapamil mean arterial blood pressures (MABPs), heart rates, intracranial pressures (ICPs) (when available), and visible changes in the degree of vasospasm. Results No statistically significant changes in MABP, heart rate, or ICP were observed after administration of ≥ 20 mg of intraarterial verapamil, and the degree of improvement in vasospasm was statistically significant based on our grading system. No correlation was found between the change in hemodynamic parameters and the total dose of verapamil. Conclusions This study indicates that high-dose intraarterial verapamil may be used to treat cerebral vasospasm without compromising hemodynamic stability or increasing ICP.


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