Journal of neurosurgery
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Journal of neurosurgery · Apr 2011
Tamoxifen as an effective neuroprotectant in an endovascular canine model of stroke.
Tamoxifen has been shown to be a potent neuroprotectant against stroke in rodents. Because other neuroprotectant medications have failed in human trials, a study of tamoxifen in a large-animal model was necessary to further assess the drug's effectiveness. For this study, the authors developed an endovascular model of anterior circulation infarction in canines to mimic the human clinical condition. They assessed the following hypotheses: 1) that they will be able to consistently produce an internal carotid artery (ICA) terminus infarction and 2) that tamoxifen is an effective neuroprotectant against stroke in canines. ⋯ Using this endovascular model of stroke, the authors were able to consistently produce an infarction in the canines that was similar in scope to a carotid terminus occlusion in humans. Also, angiography could predict subsequent clinical course and infarct size. Tamoxifen was effective at significantly improving the canine neurological deficits and reducing the size of the stroke. This study took the first step in demonstrating the effectiveness of a promising human neuroprotectant in a large animal.
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Journal of neurosurgery · Apr 2011
Anatomical triangles defining surgical routes to posterior inferior cerebellar artery aneurysms.
Surgical routes to posterior inferior cerebellar artery (PICA) aneurysms are opened between the vagus (cranial nerve [CN] X), accessory (CN XI), and hypoglossal (CN XII) nerves for safe clipping, but these routes have not been systematically defined. The authors describe 3 anatomical triangles and their relationships with PICA aneurysms, routes for surgical clipping, outcomes, and angiographically demonstrated anatomy. ⋯ The anatomical triangles and zones clarify the borders of operative corridors to PICA aneurysms and define the depth of dissection through the CNs. Deep dissection to aneurysms in the anterior medullary zone traverses CNs X, XI, and XII, whereas shallow dissection to aneurysms in the lateral medullary zone traverses CNs X and XI. Posterior inferior cerebellar artery aneurysms outside the vagoaccessory triangle are frequently distal and superficial to the lower CNs, and associated surgical morbidity is minimal. Angiography may preoperatively localize a PICA aneurysm's triangular anatomy based on the distal PICA origin or distal aneurysm location.
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Journal of neurosurgery · Apr 2011
Optimal cerebrospinal fluid magnesium ion concentration for vasodilatory effect and duration after intracisternal injection of magnesium sulfate solution in a canine subarachnoid hemorrhage model.
The optimal CSF Mg(++) concentration for vasodilation of spastic cerebral arteries after subarachnoid hemorrhage (SAH) and its duration are unknown. The temporal profile of the vasodilatory effect and optimal CSF Mg(++) concentration after the intracisternal injection of MgSO(4) solution were investigated in an SAH model in canines. ⋯ The reversible effect of an intracisternal injection of MgSO(4) solution on the spastic artery requires CSF Mg(++) concentrations > 3 mEq/L. The vasodilatory effect continues for 3-6 hours after injection. These results suggest that the continuous infusion or intermittent intracisternal injection of MgSO(4) is needed to maintain the optimal CSF Mg(++) concentration and constantly ameliorate cerebral vasospasm.
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Journal of neurosurgery · Apr 2011
Improvement in neurological outcome and abolition of cerebrovascular endothelin B and 5-hydroxytryptamine 1B receptor upregulation through mitogen-activated protein kinase kinase 1/2 inhibition after subarachnoid hemorrhage in rats.
Delayed cerebral ischemia after subarachnoid hemorrhage (SAH) remains a major cause of death and disability. It has been hypothesized that cerebrovascular upregulation of vasoconstrictor receptors is a key step in the development of delayed cerebral ischemia. Upregulation of endothelin-B (ET(B)) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors has been demonstrated in cerebral artery smooth muscles in the delayed ischemic phase after experimental SAH, and intracellular signaling via the mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase 1/2 pathway has been shown to be involved in this upregulation. The aim in the present study was to determine whether treatment with the MEK1/2 inhibitor U0126 can prevent cerebrovascular receptor upregulation and improve functional outcome after experimental SAH in rats. ⋯ The authors demonstrated that experimental SAH induces upregulation of ET(B) and 5-HT(1B) receptors in cerebrovascular smooth muscles and that treatment with the MEK1/2 inhibitor U0126 abolishes this receptor upregulation. They also demonstrated that experimental SAH results in sensorimotor deficits as assessed by a rotating pole test. These deficits were alleviated by U0126 treatment, suggesting that cerebrovascular receptor upregulation is critical for the functional outcome of delayed cerebral ischemia. The authors suggest that inhibition of MEK1/2 may be a promising new SAH treatment strategy.