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Table 9 Selected Studies of SAH in Rabbits Examining Mortality and Neurological Endpoints

From: Neurological and neurobehavioral assessment of experimental subarachnoid hemorrhage

Author

Model

Mortality

Behavior tests

Controls

Experimental findings

Disconnect between vasospasm and outcomes

Endo1988A

Single cisterna magna injection plus bilateral carotid occlusion

None reported after SAH, some animals died after carotid occlusion

4 point neurological grading scale consisting of 1. No neurologic deficit (normal), 2. Minimum or suspicious neurologic deficit, 3. Mild neurologic deficit without abnormal movement, 4. Severe neurologic deficit with abnormal movement

SAH or saline-injected controls

Worse behavior and production of vasospasm in SAH compared to saline-injected controls

They correlated

Otsuji1994A

Bilateral carotid occlusion, then 2 weeks later SAH followed 2 days later by cisternal injection of oxyhemoglobin

8/23 died (32%) after the second injection

4 point neurological grading scale consisting of 1. No neurologic deficit (normal), 2. Minimum or suspicious neurologic deficit, 3. Mild neurologic deficit without abnormal movement, 4. Severe neurologic deficit with abnormal movement

None

Neurological deficits in some animals

No correlation reported between neurological grade and vasospasm, there was a better correlation between CBF and neurological grade. Grade 2 and 3 had about 25% vasospasm and grade 4 had 40% so at least the most markedly worse neurological grade had more vasospasm

Nomura1998

Bilateral carotid occlusion, then 5 weeks later SAH by single cisterna magna injection

0/9 SAH, 3/8 SAH + immunization with subcutaneous cardiolipin antigen, 5/12 SAH + intravenous cardiolipin antigen, 0/8 SAH plus intravenous cardiolipin antigen + dexamethasone + cyclosporin A

4 point neurological grading scale consisting of 1. No neurologic deficit (normal), 2. Minimum or suspicious neurologic deficit, 3. Mild neurologic deficit without abnormal movement, 4. Severe neurologic deficit with abnormal movement

None

Neurologic deficits and vasospasm worse with SAH plus intravenous cardiolipin antigen compared to SAH alone whereas cyclosporin + dexamethasone reversed this to the SAH alone level

They correlated

Buemi2000

Single cisterna magna injection, no ICP monitoring

0% with control or SAH + erythropoeitin, 43% SAH + vehicle

Open field locomotor activitiy

Probably normal rabbits

Erythropoeitin improved locomotor activity, one comment that that there was no corrugation of the internal elastic lamina in animals treated with erythropoeitin

Not assessed

Grasso2002

Single cisterna magna injection, no ICP monitoring

None reported

Daily 4 point neurological assessment of normal (1), minimal or suspected deficit (2), mild deficit (3) or severe deficit with abnormal movements (4)

SAH or control, unoperated animals

Erythropoeitin improved neurological status, decreased necrotic cortical neurons and vasospasm

They correlated

Zhou2007A

1 or 2 injections into cisterna magna, 1.5 ml blood once or twice over 1 minute, no ICP monitoring

0% single, 6% double hemorrhage

Vasospasm, mortality, clinical assessment by the 6 point scale {Zhou2005}

SAH or control, unoperated animals

Only significant behavior difference was poor appetite in double hemorrhage group, vasospasm in both groups, a little less with single hemorrhage

They correlated

Laslo2008

Single cisterna magna injection, no ICP monitoring

10/25 (40%) SAH died, no sham-operated controls died

Vasospasm and neurological scale of posture, gait, and righting reflexes (each given a score: 0 normal, 1 mild, 2 moderate and 3 severely impaired. Front and back reflexes were also scored 0 normal, 1 brisk, 2 spreading and 3 clonus

SAH or saline-injected controls

Neurological function worse with SAH and with more severe vasospasm

They correlated

Tang2008

Right common carotid artery ligation + single cisterna magna blood injection

None reported

4 point neurological grading scale consisting of 1. No neurologic deficit (normal), 2. Minimum or suspicious neurologic deficit, 3. Mild neurologic deficit without abnormal movement, 4. Severe neurologic deficit with abnormal movement

None

Neurological function and vasospasm decreased by ecdysterone

They correlated