Table 8

Selected Studies of SAH in Mice Examining Mortality and Neurological Endpoints

    Author

    Model

    Mortality

    Behavior tests

    Controls

    Experimental findings

    Disconnect between vasospasm and outcomes


Parra2002

Endovascular perforation

none reported

Neurobehavior score of 5-27 72 hours after SAH, combined from 2 prior scales {Garcia1995}{Crawley2000}, comprised of motor (0-12) spontaneous activity, symmetry of limb movements, climbing, balance and coordination and sensory (5-15) which was proprioception, vibrissae, visual, olfactory and tactile responses.

SAH or sham-operated controls

72 hours after SAH, body weight reduced in SAH group, neurological function worse, correlated with vasospasm and SAH grading.

They correlated

McGirt2002

Endovascular perforation

6/34 (18%) simvastatin versus 4/36 (11%) vehicle which would not be significant (Fisher's exact test) by my calculations

Neurobehavior score of 5-27 72 hours after SAH, combined from 2 prior scales {Garcia1995}{Crawley2000}, comprised of motor (0-12) spontaneous activity, symmetry of limb movements, climbing, balance and coordination and sensory (5-15) which was proprioception, vibrissae, visual, olfactory and tactile responses.

Simvastatin versus vehicle

More vasospasm and behavior deficit with SAH compared to shams and simvastatin prevented vasospasm and behavior deficits.

They correlated

McGirt2002A

Endovascular perforation

9% mortality, no statement about if it was different between groups

Neurobehavior score of 9-39 72 hours after SAH, combined from 2 prior scales {Garcia1995}{Crawley2000}, comprised of motor (0-12) spontaneous activity, symmetry of limb movements, climbing, balance and coordination and sensory (5-15) which was proprioception, vibrissae, visual, olfactory and tactile responses and reflexes (4-12) righting, postural, ear and eye

SAH in wild-type, human extracellular superoxide dismutase transgenics and sham-operated controls

More vasospasm and behavior deficit with transgenics and wild types compared to shams of both strains but no difference between transgenic and wild type, less nitrotyrosine staining in the transgenics, body weight did not differ between transgenic and wild type but unclear if this was at baseline or after SAH.

They correlated

Lin2003

Single 60 μl cisterna magna injection over 1 minute, no ICP monitoring

3%

None

SAH, saline-injected and sham-operated controls

Vasospasm could be produced, no behavior assessment

Not assessed

Gao2006

Endovascular perforation

18% of apoe3 versus 38% of apoe4 mice

Rotarod, neurological severity score consisting of motor (spontaneous activity, symmetry of limb movements, climbing and balance and coordination), sensory (body proprioception and tactile and vibrissa responses)

SAH in apoe3, apoe4, apoe4 mimetic peptide treated and sham-operated controls

SAH groups had significantly worse behavior than sham-operated controls. Among apoe animals, there was better rotarod performance and less vasospasm with apoe3 mice compared to apoe4. Apoe4 peptide mimetic reduced mortality, improved neurological score, rotarod latency and vasospasm

They correlated

Wang2006

Endovascular perforation

None reported

Rotarod, neurological severity score consisting of motor (spontaneous activity, symmetry of limb movements, climbing and balance and coordination), sensory (body proprioception and tactile and vibrissa responses)

SAH and sham-operated controls but no results of sham-operation reported

Levetiracetam improved rotarod, neurological score and vasospasm

They correlated

Mesis2006

Endovascular perforation

None reported

Rotarod, neurological severity score consisting of motor (spontaneous activity, symmetry of limb movements, climbing and balance and coordination), sensory (body proprioception and tactile and vibrissa responses)

None

Carboxyamidotriazole worsened behavioral outcome and decreased vasospasm whereas nimodipine and apo E mimetic peptide improved neurological scores, rotarod latency and decreased vasospasm.

Yes, carboxyamidotriazole worsened function and decreased vasospasm which could be due to drug toxicity, only low dose nimodipine decreased vasospasm and improved outcome whereas high dose did not and the authors suggest this proves vasospasm does not cause all deficits after SAH which is true but examination of bar graphs shows a 2 μm difference (about 2%) between the nimodipine doses


Jeon et al. BMC Neuroscience 2009 10:103   doi:10.1186/1471-2202-10-103

Open Data