Aaron S. Dumont

A murine model of subarachnoid hemorrhage-induced cerebral vasospasm

Cerebral vasospasm remains a major cause of morbidity and mortality after subarachnoid hemorrhage (SAH). The availability of a mouse model of SAH that is simple, replicable and has low mortality would provide a powerful approach for understanding cellular and molecular mechanisms contributing to post-SAH pathologies. The present study characterizes a mouse model of experimental SAH, which produces consistent constriction of large cerebral arteries. Adult mice received injections of autologous blood into the cisterna magna, and the diameters of large intracranial vessels were measured 1 h to 7 days post-SAH. A diffuse blood clot was evident in both the anterior and posterior circulations after SAH. Vascular wall thickening, lumenal narrowing and corrugation of the internal elastic lamina were observed. Both acute (6-12 h) and delayed (1-3 days) phases of vasoconstriction occurred after SAH. Overall mortality was only 3%. A reproducible, low mortality model of SAH-induced cerebral vasospasm in mice is described. This mouse model should facilitate the delineation of cellular and molecular mechanisms of SAH-induced pathologies because of the widespread availability of various technologies for this species (e.g. genetically-altered animals and gene expression arrays). This model also represents a replicable and inexpensive approach for screening therapeutic candidates.

Part II: spinal-cord neoplasms--primary tumours of the bony spine and adjacent soft tissues.

Primary tumours of the bony spine and adjacent soft tissues most frequently present with pain although neurological deficits and spinal deformity can be present too. Knowledge of the spectrum of lesions that can affect the bony spine and the surrounding soft tissues is crucial in directing appropriate investigation and treatment. Patients need individualised approaches and treatment plans in view of the variations in tumour aggressiveness, spinal level, location within the vertebral body or posterior elements, involvement of soft tissues and structures surrounding the vertebral column, neurological deficits, and spinal instability.

17β-Estradiol Activates Adenosine A2a Receptor After Subarachnoid Hemorrhage

BACKGROUNDnOur previous study showed that 17beta-estradiol (E2) and an adenosine A(2A) receptor (AR-A(2A)) agonist could attenuate subarachnoid hemorrhage (SAH)-induced cerebral vasospasm via preventing the augmentation of iNOS expression and preserving the normal eNOS expression. This study tests the hypothesis that E2 attenuates SAH-induced vasospasm and apoptosis by activating adenosine AR-A(2A) and extracellular signal-regulated kinase 1 and 2 (ERK1/2), and by altering antiapoptotic and proapoptotic protein expression (Bcl-2 and Bax, respectively).nnnMATERIALS AND METHODSnThe two-hemorrhage SAH model in rat was used. Animals were treated with E2 with or without a nonselective estrogen receptor (ER) antagonist (ICI182,780). The cross sectional areas of the basilar artery and terminal dUTP nick-end labeling (TUNEL) were used to determine the degree of vasospasm and apoptosis, respectively. The expressions of Bcl-2, Bax, AR-A(2A), and ERK1/2 in the cerebral cortex, hippocampus, and dentate gyrus were investigated.nnnRESULTSnE2 significantly attenuated vasospasm. Seven days after the first SAH, TUNEL scores were significantly increased, and protein levels of AR-A(2A), ERK1/2, and Bcl-2 were significantly decreased in the dentate gyrus only but not in the cortex and hippocampus. These changes were reversed by E2 while ICI182,780 abrogated the antiapoptotic and anti-spastic effects of E2. The expression of Bax did not change in the dentate gyrus after SAH with or without treatment.nnnCONCLUSIONSnThe down-regulated AR-A(2A) and ERK may play a role in vasospasm and apoptosis after SAH. The beneficial effect of E2 in the attenuating SAH-induced vasospasm and apoptosis may be due to an increased expression of AR-A(2A) and ERK via ER-dependent mechanisms. These data may support further investigation of E2 in the treatment of SAH in humans.

The effect of an adenosine A1 receptor agonist in the treatment of experimental subarachnoid hemorrhage-induced cerebrovasospasm

SummaryBackground. Adenosine is a potent vasodilator and an important modulator of cardiovascular function. It has been postulated that nitric oxide (NO) is involved in adenosine-induced vasodilation. This study was designed to examine the effect of an adenosine A1 agonist, N6-cyclopentyladenosine (CPA), in the prevention of subarachnoid haemorrhage (SAH)-induced vasospasm.n Method. Experimental SAH was induced in Sprague-Dawley rats by injecting 0.3u2009mL autogenous blood into the cisterna magna. Intraperitoneal injections of CPA (0.003u2009mg/kg), or vehicle were administered 5u2009min and 24 hours after induction of SAH. The degree of vasospasm was determined by averaging the cross sectional areas of the basilar artery 2 days after SAH. Expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basilar artery were evaluated.n Findings. There were no significant differences among the control and treated groups in physiological parameters recorded before sacrifice. When compared with animals in the control group, cross-sectional area of basilar arteries areas in the SAH only, SAH plus vehicle and SAH plus CPA groups were reduced by 19% (p < 0.01), 22% (p < 0.01), and 9% (p = 0.133), respectively. The cross-sectional areas of the CPA-treated group differed significantly from those of the SAH only and SAH plus vehicle group (p < 0.05). Induction of iNOS-mRNA and protein in basilar artery by SAH was not significantly diminished by CPA. The SAH-induced suppression of eNOS-mRNA and protein were relieved by CPA treatment.n Conclusions. This is the first evidence to show an adenosine A1 receptor agonist is effective in partially preventing SAH-induced vasospasm without significant cardiovascular complications. The mechanisms of adenosine A1 receptor agonists in attenuating SAH-induced vasospasm may be, in part, related to preserve the normal eNOS expression after SAH. Inability in reversing the increased iNOS expression after SAH may lead to the incomplete anti-spastic effect of CPA.

Positioning for Cranial Surgery

Although it is not always adequately emphasized, positioning of the patient for intracranial procedures remains a critical step in a successful surgery. Optimal positioning allows the surgical team to complete their objective in the most effective fashion in many ways; for example, ideal positioning may reduce or eliminate the need for brain retraction, help provide a clear and bloodless field, reduce intracranial pressure and avoid venous obstruction, present the anatomy and pathology in the ideal perspective for the surgeon, and minimize the chance of avoidable complications such as brachial plexus stretch injuries and pressure neuropathies. This chapter reviews fundamental principles of positioning for the most common approaches to cranial disease.

Pituitary Tumors in Children

Pituitary tumors are relatively uncommon in the pediatric population and most commonly present during adolescence. The average annual incidence has been estimated at two per million children, comprising about 8% of all intracranial tumors of childhood [3]. In contrast to adults, prolactin (PRL)- and adrenocortico-tropic (ACTH)-secreting adenomas appear to be most common, while nonfunctioning tumors appear to be rare [20, 22].

CHAPTER 2 – Subarachnoid Hemorrhage

Publisher Summary nThis chapter focuses on neurological clinical trials related to subarachnoid hemorrhage (SAH) and the epidemiology, etiology, and diagnosis of SAH. The management of SAH and vasospasm remains challenging, with few proven interventions that alter clinical outcomes. Currently, the only regularly used intervention in North America with some evidence from clinical trials supporting their efficacy include early definitive therapy, seizure prophylaxis, electrolyte normalization, intracerebral pressure monitoring and correction, nimodipine, triple H therapy composed of hypertension, hypervolemia, and hemodilution (HHH therapy), balloon angioplasty, and intra-arterial papaverine therapy. Although numerous clinical trials have been conducted in search of interventions that may alter outcomes, most have shown a little, no, or inconsistent benefits of proposed interventions, compared with placebo. The failure of these clinical trials is multifactorial, related to the underlying complexity of the mechanisms resulting in vasospasm, the failure of clinical trials to recruit enough participants to provide adequate power to assess the efficacy of interventions, and the lack of appropriate, sensitive, and specific measures of clinical endpoints. Even so, the morbidity and mortality of vasospasm are theoretically preventable. Therefore, it is critical that clinical trials continue to investigate means of preventing early rebleeding, maintaining perfusion, and preventing vascular constriction and subsequent neurological deterioration.