Medicine and Health Sciences Commons^™

Developing Novel Therapies For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 7]: Opportunities From Restorative Neurobiology., Aref-Ali Gharooni, Brian K Kwon, Michael G Fehlings, Timothy F Boerger, Ricardo Rodrigues-Pinto, Paul Aarne Koljonen, Shekar N Kurpad, James Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Jefferson R Wilson, Benjamin M Davies, Mark R N Kotter, James D Guest

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To provide an overview of contemporary therapies for the James Lind Alliance priority setting partnership for degenerative cervical myelopathy (DCM) question: 'Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, be identified to improve the health and wellbeing of people living with DCM and slow down disease progression?'

Methods: A review of the literature was conducted to outline the pathophysiology of DCM and present contemporary therapies that may hold therapeutic value in 3 broad categories of neuroprotection, neuroregeneration, and neuromodulation.

Results: Chronic spinal cord compression leads to ischaemia, neuroinflammation, demyelination, and neuronal loss. Surgical …

Aneurysm Formation, Growth, And Rupture: The Biology And Physics Of Cerebral Aneurysms., Pavlos Texakalidis, Ahmad Sweid, Nikolaos Mouchtouris, Eric C. Peterson, Chrissa Sioka, Leonardo Rangel-Castilla, John Reavey-Cantwell, Pascal Jabbour

Department of Neurosurgery Faculty Papers

Cerebral aneurysms (CAs) are characterized by a pathological wall structure with internal elastic lamina and media disruption, which leads to focal weakened pouches of the arterial wall. The prevalence of unruptured CAs has been estimated to be 2%-5% in the general population. During the past few decades, the pathophysiological mechanisms behind the formation, growth, and rupture of CAs have been the focus of numerous research studies. In the present review, we have summarized the inflammatory pathways, genetics, and risk factors for the formation, growth, and rupture of CAs. In addition, we have discussed the concepts of geometric indexes, flow patterns, …

Migraine And Vascular Disease Biomarkers: A Population-Based Case-Control Study., Gretchen E. Tietjen, Jagdish Khubchandani, Nabeel Herial, Inge H. Palm-Meinders, Hille Koppen, Gisela M. Terwindt, Mark A. Van Buchem, Lenore J. Launer, Michel D. Ferrari, Mark C. Kruit

Department of Neurosurgery Faculty Papers

Background The underpinnings of the migraine-stroke association remain uncertain, but endothelial activation is a potential mechanism. We evaluated the association of migraine and vascular disease biomarkers in a community-based population. Methods Participants (300 women, 117 men) were recruited as a part of the Dutch CAMERA 1 (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) study. Participants were aged 30-60 (mean 48) years, 155 migraine had with aura (MA), 128 migraine without aura (MO), and 134 were controls with no severe headaches. Plasma concentrations of fibrinogen, Factor II, D-dimer, high sensitivity C-reactive protein (hs-CRP), and von Willebrand factor antigen were compared …

Sex Differential In 15-Hydroxyprostaglandin Dehydrogenase Levels In The Lumen Of Human Intracranial Aneurysms., Nohra Chalouhi, Pascal Jabbour, Mario Zanaty, Robert M. Starke, James Torner, Daichi Nakagawa, David M. Hasan

Department of Neurosurgery Faculty Papers

BACKGROUND: Aspirin is a promising medical therapy for the prevention of intracranial aneurysm (IA) rupture. Recently, we found that men have a better response to aspirin than women. The purpose of this study was to determine whether a sex differential exists in the level of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) in the lumen of human IAs.

METHODS AND RESULTS: Consecutive patients undergoing coiling or stent-assisted coiling for a saccular IA at our institution were enrolled. Two samples (A and B) were collected from IA lumens, and the plasma level of 15-PGDH was measured using an ELISA-based method. The study included 38 patients, …

Therapeutic Implications Of Estrogen For Cerebral Vasospasm And Delayed Cerebral Ischemia Induced By Aneurysmal Subarachnoid Hemorrhage., Dale Ding, Robert M Starke, Aaron S Dumont, Gary K Owens, David M Hasan, Nohra Chalouhi, Md, Ricky Medel, Chih-Lung Lin

Department of Neurosurgery Faculty Papers

Cerebral vasospasm (CV) remains the leading cause of delayed morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). However, increasing evidence supports etiologies of delayed cerebral ischemia (DCI) other than CV. Estrogen, specifically 17 β -estradiol (E2), has potential therapeutic implications for ameliorating the delayed neurological deterioration which follows aneurysmal SAH. We review the causes of CV and DCI and examine the evidence for E2-mediated vasodilation and neuroprotection. E2 potentiates vasodilation by activating endothelial nitric oxide synthase (eNOS), preventing increased inducible NOS (iNOS) activity caused by SAH, and decreasing endothelin-1 production. E2 provides neuroprotection by increasing thioredoxin expression, decreasing c-Jun N-terminal …