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https://www.readbyqxmd.com/read/27617002/mechanism-of-action-and-clinical-potential-of-fingolimod-for-the-treatment-of-stroke
#1
Wentao Li, Haoliang Xu, Fernando D Testai
Fingolimod (FTY720) is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood-brain barrier permeability, and cell survival in the event of cerebrovascular insult...
2016: Frontiers in Neurology
https://www.readbyqxmd.com/read/27412141/racial-ethnic-disparities-in-acute-blood-pressure-after-intracerebral-hemorrhage
#2
Sebastian Koch, Mitchell S V Elkind, Fernando D Testai, W Mark Brown, Sharyl Martini, Kevin N Sheth, Ji Y Chong, Jennifer Osborne, Charles J Moomaw, Carl D Langefeld, Ralph L Sacco, Daniel Woo
OBJECTIVE: To assess race-ethnic differences in acute blood pressure (BP) following intracerebral hemorrhage (ICH) and the contribution to disparities in ICH outcome. METHODS: BPs in the field (emergency medical services [EMS]), emergency department (ED), and at 24 hours were compared and adjusted for group differences between non-Hispanic black (black), non-Hispanic white (white), and Hispanic participants in the Ethnic Racial Variations of Intracerebral Hemorrhage case-control study...
August 23, 2016: Neurology
https://www.readbyqxmd.com/read/26850978/incontinence-and-gait-disturbance-after-intraventricular-extension-of-intracerebral-hemorrhage
#3
MULTICENTER STUDY
Daniel Woo, Andrew J Kruger, Padmini Sekar, Mary Haverbusch, Jennifer Osborne, Charles J Moomaw, Sharyl Martini, Shahla M Hosseini, Simona Ferioli, Bradford B Worrall, Mitchell S V Elkind, Gene Sung, Michael L James, Fernando D Testai, Carl D Langefeld, Joseph P Broderick, Sebastian Koch, Matthew L Flaherty
OBJECTIVE: We tested the hypothesis that intraventricular hemorrhage (IVH) is associated with incontinence and gait disturbance among survivors of intracerebral hemorrhage (ICH) at 3-month follow-ups. METHODS: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was used as the discovery set. The Ethnic/Racial Variations of Intracerebral Hemorrhage study served as a replication set. Both studies performed prospective hot-pursuit recruitment of ICH cases with 3-month follow-up...
March 8, 2016: Neurology
https://www.readbyqxmd.com/read/26773687/intracerebroventricular-application-of-s100b-selectively-impairs-pial-arteriolar-dilating-function-in-rats
#4
Benjarat Changyaleket, Haoliang Xu, Francesco Vetri, Tibor Valyi-Nagy, Chanannait Paisansathan, Zhao Zhong Chong, Dale A Pelligrino, Fernando D Testai
S100B is an astrocyte-derived protein that can act through the receptor for advanced glycation endproducts (RAGE) to mediate either "trophic" or "toxic" responses. Its levels increase in many neurological conditions with associated microvascular dysregulation, such as subarachnoid hemorrhage (SAH) and traumatic brain injury. The role of S100B in the pathogenesis of microvasculopathy has not been addressed. This study was designed to examine whether S100B alters pial arteriolar vasodilating function. Rats were randomized to receive (1) artificial cerebrospinal fluid (aCSF), (2) exogenous S100B, and (3) exogenous S100B+the decoy soluble RAGE (sRAGE)...
March 1, 2016: Brain Research
https://www.readbyqxmd.com/read/25917010/feasibility-of-assessment-of-conjunctival-microvascular-hemodynamics-in-unilateral-ischemic-stroke
#5
Ali Kord Valeshabad, Justin Wanek, Faisal Mukarram, Ruth Zelkha, Fernando D Testai, Mahnaz Shahidi
Since the internal carotid artery supplies blood to both the eye and the brain, ocular microvascular hemodynamics can be altered due to ischemic stroke. The purpose of the current study was to establish the feasibility of conjunctival microcirculation imaging for detection of inter-ocular differences in microvascular hemodynamics in subjects with unilateral ischemic stroke. Conjunctival microcirculation imaging was performed in both eyes of 15 healthy control subjects and 12 subjects following unilateral ischemic stroke...
July 2015: Microvascular Research
https://www.readbyqxmd.com/read/25694554/a-single-nucleotide-polymorphism-in-serine-threonine-kinase-11-the-gene-encoding-liver-kinase-b1-is-a-risk-factor-for-multiple-sclerosis
#6
Anne I Boullerne, Demetrios Skias, Elizabeth M Hartman, Fernando D Testai, Sergey Kalinin, Paul E Polak, Douglas L Feinstein
We identified a family in which five siblings were diagnosed with multiple sclerosis (MS) or clinically isolated syndrome. Several women in the maternal lineage have comorbidities typically associated with Peutz Jeghers Syndrome, a rare autosomal-dominant disease caused by mutations in the serine-threonine-kinase 11 (STK11) gene, which encodes liver kinase B1. Sequence analysis of DNA from one sibling identified a single-nucleotide polymorphism (SNP) within STK11 intron 5. This SNP (dbSNP ID: rs9282860) was identified by TaqMan polymerase chain reaction (PCR) assays in DNA samples available from two other siblings...
January 2015: ASN Neuro
https://www.readbyqxmd.com/read/25662771/vap-1-blockade-prevents-subarachnoid-hemorrhage-associated-cerebrovascular-dilating-dysfunction-via-repression-of-a-neutrophil-recruitment-related-mechanism
#7
Haoliang Xu, Fernando D Testai, Tibor Valyi-Nagy, Mani N Pavuluri, Fengguo Zhai, Danop Nanegrungsunk, Chanannait Paisansathan, Dale A Pelligrino
Our previous findings indicated that in rats subjected to subarachnoid hemorrhage (SAH), suppression of post-SAH neuroinflammation via vascular adhesion protein-1 (VAP-1) blockade provides significant neuroprotection. We and others have reported that neuroinflammation contributes to cerebral microvascular impairment. Thus, in the present study, we tested the hypotheses that: (1) treatment with LJP-1586, a selective VAP-1 blocker, prevents SAH-associated pial arteriolar dilating dysfunction; and (2) the vasculoprotective effect of LJP-1586 arises from inhibiting SAH-elicited neutrophil recruitment...
April 7, 2015: Brain Research
https://www.readbyqxmd.com/read/25622980/protective-role-of-fingolimod-fty720-in-rats-subjected-to-subarachnoid-hemorrhage
#8
Hao-Liang Xu, Dale A Pelligrino, Chanannait Paisansathan, Fernando D Testai
BACKGROUND: Subarachnoid hemorrhage (SAH) is a neurological emergency with limited pharmacological treatment options. Inflammation is increasingly recognized as a key pathogenic contributor to brain injury in this condition. In the present study, we examined the neuroprotective effects of the immunomodulatory agent, fingolimod, in rats subjected to SAH. METHODS: We utilized an endovascular rat perforation model of SAH. Animals were divided into four groups: (1) sham-vehicle; (2) sham-fingolimod; (3) SAH-vehicle; and (4) SAH-fingolimod...
2015: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/25597763/changes-in-the-metabolism-of-sphingolipids-after-subarachnoid-hemorrhage
#9
Fernando D Testai, Hao-Liang Xu, John Kilkus, Vidyani Suryadevara, Irina Gorshkova, Evgeny Berdyshev, Dale A Pelligrino, Glyn Dawson
We previously described how ceramide (Cer), a mediator of cell death, increases in the cerebrospinal fluid (CSF) of subarachnoid hemorrhage (SAH) patients. This study investigates the alterations of biochemical pathways involved in Cer homeostasis in SAH. Cer, dihydroceramide (DHC), sphingosine-1-phosphate (S1P), and the activities of acid sphingomyelinase (ASMase), neutral sphingomyelinase (NSMase), sphingomyelinase synthase (SMS), S1P-lyase, and glucosylceramide synthase (GCS) were determined in the CSF of SAH subjects and in brain homogenate of SAH rats...
May 2015: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/25444026/cerebral-aspergillosis-in-a-diabetic-patient-leading-to-cerebral-artery-occlusion-and-ischemic-stroke-a-case-report-and-literature-review
#10
REVIEW
Wentao Li, Neelofer Shafi, Ramayee Periakaruppan, Tibor Valyi-Nagy, John Groth, Fernando D Testai
Cerebral aspergillosis is a rare and highly fatal hematogenous infection most commonly found in immune compromised patients. From the onset of neurologic symptoms, the median reported rate of survival is between 5 and 9 days. Compounded with increased hemorrhagic risks and the lack of specificity in both clinical presentation and traditional imaging, a fast and noninvasive method of definitive diagnosis is necessary if there is to be any hope for positive outcomes. We describe the case of a 50-year-old female diabetic with a history of otitis media, an uncharacterized inflammatory nasopharyngeal process, and prior ischemic strokes who presented with a new cerebral infarction in the setting of an angioinvasive fungal infection of the large cerebral arteries...
January 2015: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/25440332/a-prototype-worldwide-survey-of-diagnostic-and-treatment-modalities-for-stroke
#11
Venkatesh Aiyagari, Dilip K Pandey, Fernando D Testai, Rebbeca A Grysiewicz, Alexander Tsiskaridze, Claudio Sacks, Yomi Ogun, Olubunmi A Ogunrin, Basim M Uthman, Patrice Lindsay, Philip B Gorelick
Stroke is a global health problem. However, very little is known about stroke care in low- to middle-income countries. Obtaining country-specific information could enable us to develop targeted programs to improve stroke care. We surveyed neurologists from 12 countries (Chile, Georgia, Nigeria, Qatar, India, Lithuania, Kazakhstan, Indonesia, Denmark, Brazil, Belgium, and Bangladesh) using a web-based survey tool. Data were analyzed both for individual countries and by income classification (low income, lower middle income, upper middle income, and high income)...
February 2015: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/25175836/pharmacologic-blockade-of-vascular-adhesion-protein-1-lessens-neurologic-dysfunction-in-rats-subjected-to-subarachnoid-hemorrhage
#12
Hao-Liang Xu, Maggie Garcia, Fernando Testai, Francesco Vetri, Alexandra Barabanova, Dale A Pelligrino, Chanannait Paisansathan
Aneurysmal subarachnoid hemorrhage (SAH) is a potentially devastating clinical problem. Despite advances in the diagnosis and treatment of SAH, outcome remains unfavorable. An increased inflammatory state, one that is characterized by enhanced leukocyte trafficking has been reported to contribute to neuronal injury in association with multiple brain insults, including hemorrhagic and ischemic stroke. This study was designed to investigate, in rats, the neuropathologic consequences of heightened leukocyte trafficking following SAH, induced via endovascular perforation of the anterior cerebral artery...
October 24, 2014: Brain Research
https://www.readbyqxmd.com/read/25074747/neurogenesis-and-inflammation-after-ischemic-stroke-what-is-known-and-where-we-go-from-here
#13
REVIEW
Matthew K Tobin, Jacqueline A Bonds, Richard D Minshall, Dale A Pelligrino, Fernando D Testai, Orly Lazarov
This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra...
October 2014: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/24021679/the-ethnic-racial-variations-of-intracerebral-hemorrhage-erich-study-protocol
#14
RANDOMIZED CONTROLLED TRIAL
Daniel Woo, Jonathan Rosand, Chelsea Kidwell, Jacob L McCauley, Jennifer Osborne, Mark W Brown, Sandra E West, Eric W Rademacher, Salina Waddy, Jamie N Roberts, Sebastian Koch, Nicole R Gonzales, Gene Sung, Steven J Kittner, Lee Birnbaum, Michael Frankel, Fernando Daniel Testai, Christiana E Hall, Mitchell S V Elkind, Matthew Flaherty, Bruce Coull, Ji Y Chong, Tanya Warwick, Marc Malkoff, Michael L James, Latisha K Ali, Bradford B Worrall, Floyd Jones, Tiffany Watson, Anne Leonard, Rebecca Martinez, Ralph I Sacco, Carl D Langefeld
BACKGROUND AND PURPOSE: Epidemiological studies of intracerebral hemorrhage (ICH) have consistently demonstrated variation in incidence, location, age at presentation, and outcomes among non-Hispanic white, black, and Hispanic populations. We report here the design and methods for this large, prospective, multi-center case-control study of ICH. METHODS: The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case-control study of ICH...
October 2013: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/22968344/the-dementia-of-cardiac-disease
#15
REVIEW
Hurmina Muqtadar, Fernando D Testai, Philip B Gorelick
Cardiovascular disease and dementia are common in the elderly and are major causes of disability in the general population. The public health burden of dementia is projected to increase as life expectancy increases in the United States and elsewhere. Epidemiological studies suggest that these once believed unrelated conditions, heart disease and dementia, may be linked by shared common risks and pathogenic elements. These observations have sparked the notion that prevention or modification of certain vascular risk factors and proper management of cardiovascular disease may prevent the development or progression of dementia including Alzheimer's disease...
December 2012: Current Cardiology Reports
https://www.readbyqxmd.com/read/22713492/changes-in-the-cerebrospinal-fluid-ceramide-profile-after-subarachnoid-hemorrhage
#16
Fernando D Testai, Maureen Hillmann, Sepideh Amin-Hanjani, Irina Gorshkova, Evgeny Berdyshev, Philip B Gorelick, Glyn Dawson
BACKGROUND AND PURPOSE: The purpose of this study was to investigate changes in the cerebrospinal fluid sphingolipid profile in patients with subarachnoid hemorrhage in relation to the occurrence of symptomatic vasospasm and outcome at hospital discharge. METHODS: The ceramide profile in the cerebrospinal fluid was determined by mass spectrometry in control subjects and patients with Fisher 3 grade subarachnoid hemorrhage within 48 hours of the bleed. Patients were prospectively followed and subcategorized based on the occurrence of symptomatic vasospasm and modified Rankin Scale at discharge...
August 2012: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/22528196/single-gene-disorders-associated-with-stroke-a-review-and-update-on-treatment-options
#17
Hurmina Muqtadar, Fernando D Testai
Single gene stroke disorders are rare but important to consider in the differential diagnosis of cryptogenic stroke. The identification of these disorders has a significant prognostic value and may be instrumental in the development of an appropriate stroke prevention plan. In this review we summarize the clinical features, diagnosis, and treatment of the following single gene disorders: cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL); cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL); Fabry disease; sickle cell disease; and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)...
June 2012: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/21590494/proof-of-concept-endogenous-antiangiogenic-factors-predict-the-occurrence-of-symptomatic-vasospasm-post-subarachnoid-hemorrhage
#18
Fernando D Testai, Venkatesh Aiyagari, Maureen Hillmann, Sepideh Amin-Hanjani, Glyn Dawson, Philip Gorelick
BACKGROUND: The pathogenesis of vasospasm (VS) post aneurysmal subarachnoid hemorrhage (SAH) is multifactorial and not completely understood. The authors hypothesize that circulating antiangiogenic factors play an important role in brain injury post SAH and that elevated levels predict the occurrence of symptomatic vasospasm. METHODS: In this study the authors measured the serum and cerebrospinal fluid (CSF) levels of soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in controls and SAH patients within 48 h of the bleed...
December 2011: Neurocritical Care
https://www.readbyqxmd.com/read/21443070/recurrent-posterior-reversible-encephalopathy-syndrome-in-a-sickle-cell-patient
#19
Anjana Nair, Fernando D Testai
Posterior reversible encephalopathy syndrome (PRES) in sickle cell patients has been rarely reported previously in the setting of severe crisis or uncontrolled hypertension. Here, we report a rare and unusual case of recurrent PRES in a young adult sickle cell patient without any obvious precipitating factors.
February 2011: Journal of the National Medical Association
https://www.readbyqxmd.com/read/20847949/an-unusual-cause-of-vertebral-artery-dissection-esophagogastroduodenoscopy
#20
Fernando D Testai, Philip B Gorelick
Brain-supplying arterial dissection is considered one of the most common vascular causes of stroke in younger patients. Dissections are usually preceded by trauma or mechanical stress; the vascular stressor may be trivial as this condition has been described in association with manipulation and stretching the neck. Here we describe a case of vertebral artery dissection and stroke following esophagogastroduodenoscopy. This case highlights a potentially serious complication that may occur after procedures that require hyperextension of the neck...
2010: Stroke Research and Treatment
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