Blood clot placement model of subarachnoid hemorrhage in non-human primates.

Despite ongoing extensive and promising research to prevent and treat cerebrovascular vasospasm and delayed ischemic neurological deficits (DIND) after aneurysmal subarachnoid hemorrhage (aSAH), clinical outcomes remain unsatisfying. Neuroprotective strategies developed in basic science research laboratories need to be translated from bench-to-bedside using appropriate animal models. While a primate model is widely accepted as the best animal model mimicking development of delayed cerebral vasospasm after aSAH, its worldwide usage has dramatically decreased because of ethical and financial limitations.

Estrogen induces nitric oxide production via nitric oxide synthase activation in endothelial cells.

Introduction: 17β-estradiol (E2) has been found to induce vasodilation in the cardiovascular system and at physiological levels, resulting in prevention of cerebral vasospasm following subarachnoid hemorrhage (SAH) in animal models. The goal of this study was to analyze the cellular mechanism of nitric oxide (NO) production and its relation to E2, in vitro in brain and peripheral endothelial cells.

Methods: Human umbilical endothelial cells (HUVEC) and brain endothelial cells (bEnd.

Effect of primary empty sella syndrome on pituitary surgery for Cushing's disease.

Object: Primary empty sella syndrome (ESS) results from herniation of arachnoid mater into the pituitary fossa. It has been suggested to have a negative effect on pituitary surgery; however, outcomes in this cohort have not been defined. This study was performed to determine the effect of ESS on immediate and long-term biochemical outcome after pituitary surgery for Cushing's disease (CD).

Prospective natural history study of central nervous system hemangioblastomas in von Hippel-Lindau disease.

Object: The tumors most frequently associated with von Hippel-Lindau (VHL) disease are hemangioblastomas. While they are associated with significant neurological impairment and mortality, their natural history and optimal management have not been fully defined.

Methods: Patients with VHL were enrolled in a prospective study designed to define the natural history of CNS hemangioblastomas.

Normalization of hindbrain morphology after decompression of Chiari malformation Type I.

Object: Chiari malformation Type I (CM-I) is characterized by hindbrain deformity. We investigated the effects of craniocervical decompression surgery on the anatomical features of hindbrain deformity with a prospective MRI study of patients with CM-I.

Methods: A prospective longitudinal study was conducted in 48 patients with CM-I (39 with syringomyelia) treated with craniocervical decompression.

Effect of pregnancy on hemangioblastoma development and progression in von Hippel-Lindau disease.

Object: Prior cases suggest that pregnancy increases the development and progression of CNS hemangioblastomas and/or peritumoral cysts. To determine the effect of pregnancy on CNS hemangioblastomas and peritumoral cysts, the authors prospectively evaluated serial clinical and imaging findings in patients with von Hippel-Lindau (VHL) disease who became pregnant and compared findings during pregnancy to findings in the same patients when they were not pregnant as well as to findings from a cohort of VHL patients who did not become pregnant.

Methods: Female VHL disease patients enrolled in a prospective natural history study who were of reproductive age (16-35 years at study entrance) were included.

Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid hemorrhage in primates.

Object: Subarachnoid hemorrhage (SAH)-induced vasospasm is a significant underlying cause of aneurysm rupture-related morbidity and death. While long-term intravenous infusion of sodium nitrite (NaNO(2)) can prevent cerebral vasospasm after SAH, it is not known if the intravenous administration of this compound can reverse established SAH-induced vasospasm. To determine if the intravenous infusion of NaNO(2) can reverse established vasospasm, the authors infused primates with the compound after SAH-induced vasospasm was established.

Carbon dioxide influence on nitric oxide production in endothelial cells and astrocytes: cellular mechanisms.

Cerebral vessels may regulate cerebral blood flow by responding to changes in carbon dioxide (CO(2)) through nitric oxide (NO) production. To better determine the role of NO production by human adult cerebral microvascular endothelial cells and human fetal astrocytes under different CO(2) conditions, we studied endothelial cell and astrocyte production of NO under hypo-, normo- and hypercapnic conditions. Human cerebral endothelial cell and fetal astrocyte cultures were exposed to hypocapnic (pCO(2) 21.

Safety and feasibility of long-term intravenous sodium nitrite infusion in healthy volunteers.

Background: Infusion of sodium nitrite could provide sustained therapeutic concentrations of nitric oxide (NO) for the treatment of a variety of vascular disorders. The study was developed to determine the safety and feasibility of prolonged sodium nitrite infusion.

Methodology: Healthy volunteers, aged 21 to 60 years old, were candidates for the study performed at the National Institutes of Health (NIH; protocol 05-N-0075) between July 2007 and August 2008.

The role of nitric oxide donors in treating cerebral vasospasm after subarachnoid hemorrhage.

Reduced intra- and perivascular availability of nitric oxide (NO) significantly contributes to the multifactorial pathophysiology of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). The short half-life of NO demands its therapeutic substitution via NO donors. Classic NO donors such as sodium nitroprusside and nitroglycerin cannot be used as routine therapeutics because of serious side effects.

Long-term outcome after resection of brainstem hemangioblastomas in von Hippel-Lindau disease.

Object: Brainstem hemangioblastomas are frequently encountered in patients with von Hippel-Lindau (VHL) disease. These tumors can cause significant morbidity, and their optimal management has not been defined. To better define the outcome and management of these tumors, the authors analyzed the long-term results in patients who underwent resection of brainstem hemangioblastomas.

Functional outcome after resection of spinal cord hemangioblastomas associated with von Hippel-Lindau disease.

Object: Spinal cord hemangioblastomas are a common protean manifestation of von Hippel-Lindau (VHL) disease and can be associated with significant morbidity. To better define expected outcome and optimal management of these tumors in the context of this neoplasia syndrome, the authors analyzed the findings from patients with VHL disease who underwent resection of spinal cord hemangioblastomas.

Methods: Consecutive patients with VHL disease who underwent surgery for spinal cord hemangioblastomas with > 6 months follow-up were included in the study.