scholarly journals A Rat Model of Prenatal Zika Virus Infection and Associated Long-Term Outcomes

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2298
Author(s):  
Morgan L. Sherer ◽  
Elise A. Lemanski ◽  
Rita T. Patel ◽  
Shannon R. Wheeler ◽  
Mark S. Parcells ◽  
...  
Keyword(s):  
Rat Model ◽  
Zika Virus ◽  
Fold Increase ◽  
Interferon Response ◽  
Motor Deficits ◽  
Long Term Outcomes ◽  
Zikv Infection ◽  
Full Spectrum ◽  
The Brain

Zika virus (ZIKV) is a mosquito-borne flavivirus that became widely recognized due to the epidemic in Brazil in 2015. Since then, there has been nearly a 20-fold increase in the incidence of microcephaly and birth defects seen among women giving birth in Brazil, leading the Centers for Disease Control and Prevention (CDC) to officially declare a causal link between prenatal ZIKV infection and the serious brain abnormalities seen in affected infants. Here, we used a unique rat model of prenatal ZIKV infection to study three possible long-term outcomes of congenital ZIKV infection: (1) behavior, (2) cell proliferation, survival, and differentiation in the brain, and (3) immune responses later in life. Adult offspring that were prenatally infected with ZIKV exhibited motor deficits in a sex-specific manner, and failed to mount a normal interferon response to a viral immune challenge later in life. Despite undetectable levels of ZIKV in the brain and serum in these offspring at P2, P24, or P60, these results suggest that prenatal exposure to ZIKV results in lasting consequences that could significantly impact the health of the offspring. To help individuals already exposed to ZIKV, as well as be prepared for future outbreaks, we need to understand the full spectrum of neurological and immunological consequences that could arise following prenatal ZIKV infection.

scholarly journals An Examination of the Long-Term Neurodevelopmental Impact of Prenatal Zika Virus Infection in a Rat Model Using a High Resolution, Longitudinal MRI Approach

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1123
Author(s):  
Rita T. Patel ◽  
Brennan M. Gallamoza ◽  
Praveen Kulkarni ◽  
Morgan L. Sherer ◽  
Nicole A. Haas ◽  
...  
Keyword(s):  
Rat Model ◽  
Zika Virus ◽  
Structural Changes ◽  
Brain Structures ◽  
Brain Regions ◽  
Female Rats ◽  
Health Concern ◽  
Zikv Infection ◽  
Male And Female Rats

Since Zika virus (ZIKV) first emerged as a public health concern in 2015, our ability to identify and track the long-term neurological sequelae of prenatal Zika virus (ZIKV) infection in humans has been limited. Our lab has developed a rat model of maternal ZIKV infection with associated vertical transmission to the fetus that results in significant brain malformations in the neonatal offspring. Here, we use this model in conjunction with longitudinal magnetic resonance imaging (MRI) to expand our understanding of the long-term neurological consequences of prenatal ZIKV infection in order to identify characteristic neurodevelopmental changes and track them across time. We exploited both manual and automated atlas-based segmentation of MR images in order to identify long-term structural changes within the developing rat brain following inoculation. The paradigm involved scanning three cohorts of male and female rats that were prenatally inoculated with 107 PFU ZIKV, 107 UV-inactivated ZIKV (iZIKV), or diluent medium (mock), at 4 different postnatal day (P) age points: P2, P16, P24, and P60. Analysis of tracked brain structures revealed significantly altered development in both the ZIKV and iZIKV rats. Moreover, we demonstrate that prenatal ZIKV infection alters the growth of brain regions throughout the neonatal and juvenile ages. Our findings also suggest that maternal immune activation caused by inactive viral proteins may play a role in altered brain growth throughout development. For the very first time, we introduce manual and automated atlas-based segmentation of neonatal and juvenile rat brains longitudinally. Experimental results demonstrate the effectiveness of our novel approach for detecting significant changes in neurodevelopment in models of early-life infections.

Visualization of immature brain lesions: MR patterns of long-term outcomes. Case reports

2021 ◽  
Vol 2 (2) ◽  
pp. 94-99
Author(s):  
Anatoly V. Anikin ◽  
Milana A. Basargina ◽  
Eugeniya V. Uvakina
Keyword(s):  
White Matter ◽  
Premature Infants ◽  
Periventricular Leukomalacia ◽  
Brain Magnetic Resonance Imaging ◽  
Brain Lesions ◽  
Gestation Period ◽  
Long Term Outcomes ◽  
Immature Brain ◽  
The Brain

The periventricular and deep white matter of the immature brain of premature infants has an increased vulnerability to various, primarily ischemic injuries. The leading mechanism of selective vulnerability of the white matter of the large hemispheres in children with a low gestation period is the lack of formation of adjacent blood circulation zones between the main arteries of the developing brain. Magnetic resonance imaging has a high sensitivity to detect damage to the brain substance, both in the acute period and in the period of long-term outcomes. Periventricular leukomalacia (PVL) is one of the variants of brain damage in premature infants and the most common term in the conclusions of diagnostic doctors (ultrasound, CT, MRI). Considering the pathomorphological criteria, not always detected changes in the white matter of the large hemispheres are PVL. Diffuse (telencephalic) gliosis and diffuse leukomalacia are ordinary and typical variants of damage to the white matter of the large hemispheres in extremely premature infants, with a gestation period of up to 30-32 weeks. In the first variant, atrophic changes predominate with a pronounced decrease in the volume of white matter and a secondary expansion of the lateral ventricles. Diffuse leukomalacia is most often mistaken for PVL, but the localization of the white matter lesion of the large hemispheres is extensive and extends beyond the peri- and paraventricular region. Clinical examples show various variants of primary non-hemorrhagic brain lesions in prematurely born children in the long-term period. The analysis of the revealed changes is carried out, taking into account current data on developing the brain and pathomorphological criteria.

Abstract TP379: “Build It and They Will Come”: How Comprehensive Stroke Certification Increases the Number of Transfers

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Betty Robertson
Keyword(s):  
Research Question ◽  
Heart Association ◽  
Fold Increase ◽  
Joint Commission ◽  
Level Of Care ◽  
Stroke Patients ◽  
Full Spectrum ◽  
Specialized Care ◽  
High Level

Introduction/Background: Stroke is the leading cause of long-term disability affecting 800,000 people in the U.S. each year. In September 2012 The Joint Commission, in collaboration with the American Heart Association/American Stroke Association’s Brain Attack Coalition, launched the Advanced Certification for Comprehensive Stroke Centers (CSCs). This new level of certification recognizes the significant resources in staff and training that comprehensive stroke centers must have to treat complex stroke. Certification is available only to comprehensive stroke centers in Joint Commission-accredited acute care hospitals. For CSC eligibility, there are numerous requirements and volumes that must be met. The most complicated stroke cases should be treated at the centers best equipped to provide specialized care that lead to better outcomes. Cedar-Sinai became the 4 th program in the nation to receive this prestigious certification. By providing expert care, numerous clinical trials, and high level treatment and procedures, we have become the center of choice for patients in need of a higher level of care. Research Question: Does comprehensive stroke certification lead to an increased number of transfers for higher level of care? Methods: Retrospective analysis of the number of acute strokes transferred to Cedars-Sinai between the first years of Comprehensive Stroke Certification in 2012 through 2015. Results: 2012 yielded a total transfer of 97 patients. In 2015 the volume had risen to 194, a 50% increase in 4 years. It is important to note that in 2014, 4 patients were transferred post TPA infusion (Drip and Ship), the gold standard for treatment of ischemic stroke. 2015 resulted in 25 such transfers, a six fold increase. Conclusion: The full spectrum and coordination of services that a CSC is equipped to provide contributes to increased access of specialized care for complex stroke patients. This in turn leads to better outcomes. This not only translates to delivery of timely optimal treatment for stroke patients, but also increases our expertise in delivery of this care.

scholarly journals The Type I Interferon Response Determines Differences in Choroid Plexus Susceptibility between Newborns and Adults in Herpes Simplex Virus Encephalitis

mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Douglas R. Wilcox ◽  
Stephen S. Folmsbee ◽  
William J. Muller ◽  
Richard Longnecker
Keyword(s):  
Choroid Plexus ◽  
Type I Interferon ◽  
Adult Brain ◽  
Interferon Response ◽  
Type I ◽  
Β Receptor ◽  
Simplex Virus ◽  
The Brain ◽  
Hsv 1

ABSTRACTNewborns are significantly more susceptible to severe viral encephalitis than adults, with differences in the host response to infection implicated as a major factor. However, the specific host signaling pathways responsible for differences in susceptibility and neurologic morbidity have remained unknown. In a murine model of HSV encephalitis, we demonstrated that the choroid plexus (CP) is susceptible to herpes simplex virus 1 (HSV-1) early in infection of the newborn but not the adult brain. We confirmed susceptibility of the CP to HSV infection in a human case of newborn HSV encephalitis. We investigated components of the type I interferon (IFN) response in the murine brain that might account for differences in cell susceptibility and found that newborns have a dampened interferon response and significantly lower basal levels of the alpha/beta interferon (IFN-α/β) receptor (IFNAR) than do adults. To test the contribution of IFNAR to restricting infection from the CP, we infected IFNAR knockout (KO) adult mice, which showed restored CP susceptibility to HSV-1 infection in the adult. Furthermore, reduced IFNAR levels did not account for differences we found in the basal levels of several other innate signaling proteins in the wild-type newborn and the adult, including protein kinase R (PKR), that suggested specific regulation of innate immunity in the developing brain. Viral targeting of the CP, a region of the brain that plays a critical role in neurodevelopment, provides a link between newborn susceptibility to HSV and long-term neurologic morbidity among survivors of newborn HSV encephalitis.IMPORTANCECompared to adults, newborns are significantly more susceptible to severe disease following HSV infection. Over half of newborn HSV infections result in disseminated disease or encephalitis, with long-term neurologic morbidity in 2/3 of encephalitis survivors. We investigated differences in host cell susceptibility between newborns and adults that contribute to severe central nervous system disease in the newborn. We found that, unlike the adult brain, the newborn choroid plexus (CP) was susceptible early in HSV-1 infection. We demonstrated that IFN-α/β receptor levels are lower in the newborn brain than in the adult brain and that deletion of this receptor restores susceptibility of the CP in the adult brain. The CP serves as a barrier between the blood and the cerebrospinal fluid and plays a role in proper neurodevelopment. Susceptibility of the newborn choroid plexus to HSV-1 has important implications in viral spread to the brain and, also, in the neurologic morbidity following HSV encephalitis.

Intradiscal O2O3: Rationale, Injection Technique, Short- and Long-term Outcomes for the Treatment of Low Back Pain Due to Disc Herniation

2017 ◽  
Vol 68 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Francesco Giurazza ◽  
Gianluigi Guarnieri ◽  
Kieran J. Murphy ◽  
Mario Muto
Keyword(s):  
Low Back Pain ◽  
Back Pain ◽  
Case Series ◽  
Radicular Pain ◽  
Motor Deficits ◽  
Injection Technique ◽  
Low Back ◽  
Long Term Outcomes ◽  
Short And Long Term

The management of low back pain should always start with a conservative approach; however, when it fails, intervention is required and at that moment the most appropriate choice remains unclear. Before invasive surgery, minimally invasive techniques can be adopted. In European trials and in a trans-Canadian clinical trial 03 ozone has been used successfully. In total over 50,000 patients have been treated safely. Ozone is a gas normally present in the atmosphere with potent oxidizing power; it has been used for percutaneous intradiscal injection combined with oxygen (O2O3) at very low concentrations for 15 years in Europe. The main indication is back pain with or without radicular pain but without motor deficits, which is refractory to 4-6 weeks of conservative therapies. Its mechanism of action on the disc is mechanical (volume reduction by subtle dehydration of the nucleus pulposis) and antinflammatory. The intradiscal ozone injection is performed with a thin needle (18-22 gauge) image guided by computed tomography or angiofluoroscopy and is usually complimented by periganglionic injection of corticosteroids and anesthetics. This combination gives immediate pain relief and allows time for the ozone to act. It is a cost-effective procedure that presents a very low complication rate (0.1%). The radicular pain is resolved before the back pain does, as is seen with microdiscectomy. Peer-reviewed publications of large randomized trials, case series, and meta analysis from large samples of patients have demonstrated the procedure to be safe and effective in the short and the long terms, with benefits recognized up to 10 years after treatment. We aim to review the principles of action of O2O3 and report the injection techniques, complications, and short- and long-term outcomes.

scholarly journals Delayed Remote Ischemic Postconditioning Improves Long Term Sensory Motor Deficits in a Neonatal Hypoxic Ischemic Rat Model

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e90258 ◽  
Author(s):  
Pradilka N. Drunalini Perera ◽  
Qin Hu ◽  
Junjia Tang ◽  
Li Li ◽  
Margaret Barnhart ◽  
...  
Keyword(s):  
Rat Model ◽  
Ischemic Postconditioning ◽  
Motor Deficits ◽  
Remote Ischemic Postconditioning ◽  
Sensory Motor

scholarly journals Zika virus: a new pandemic threat

2016 ◽  
Vol 10 (03) ◽  
pp. 201-207 ◽  
Author(s):  
Ahmed Ali Al-Qahtani ◽  
Nyla Nazir ◽  
Mashael R. Al-Anazi ◽  
Salvatore Rubino ◽  
Mohammed N. Al-Ahdal
Keyword(s):  
Zika Virus ◽  
Blood Donation ◽  
French Polynesia ◽  
Western Hemisphere ◽  
Zikv Infection ◽  
Rapid Spread ◽  
Screening And Identification ◽  
Pandemic Threat ◽  
Contaminated Blood

Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family and is related to dengue, Chikungunya, West Nile, yellow fever, and Japanese encephalitis viruses. ZIKV was first discovered in Uganda in 1947. Different species of mosquito from the Aedes genus, mainly A. aegypti and A. albopictus are the vectors responsible for ZIKV infection in humans. It is also reported that ZIKV is transmitted congenitally, sexually, and through blood donation. Until recently, ZIKV outbreaks were sporadic and self-limiting. The first large epidemic was reported from Yap Island in 2007 followed by an outbreak of Zika fever in French Polynesia in 2013. Brazil is the epicenter of the current ZIKV epidemic which is rapidly spreading across the Americas. ZIKV infection remained relatively less studied in view of its low case numbers, and low clinical impact relative to other arboviruses. However, all this is set to change with its rapid spread in the Western hemisphere and suspected complications particularly microcephaly in newborn babies with ZIKV infected mothers. ZIKV is expected to substantially add to both short-term and long-term economic burden of the effected countries. Due to the large number of people travelling across the borders and some reported cases of transmission of ZIKV via contaminated blood, screening and identification of asymptomatic infected individuals are important.

scholarly journals ADP-Ribosyltransferase PARP11 Suppresses Zika Virus in Synergy with PARP12

2021 ◽  
Author(s):  
Lili Li ◽  
Yueyue Shi ◽  
Sirui Li ◽  
Junxiao Liu ◽  
Shulong Zu ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neurological Complications ◽  
Host Cells ◽  
Interferon Response ◽  
Type I ◽  
Zikv Infection ◽  
Interferon Stimulated Genes ◽  
Ns3 Protein ◽  
Global Threat ◽  
Adp Ribosyltransferase

Abstract Zika virus (ZIKV) infection and ZIKV epidemic have been continuously spreading silently throughout the world and its associated microcephaly and other serious congenital neurological complications poses a significant global threat to public health. ZIKV infection stimulates type I interferon response in host cells which suppresses viral replication by inducing the expression of interferon-stimulated genes (ISGs). Here, we identified ADP-ribosyltransferase PARP11 as an anti-ZIKV ISG and found that PARP11 suppressed ZIKV independently on itself PARP enzyme activity. Furthermore, PARP11 interacted with PARP12 and promoted PARP12-mediating ZIKV NS1 and NS3 protein degradation. Homo family PARP11 and PARP12 cooperated with each other on ZIKV suppression and the anti-ZIKV function of PARP11 mostly dependent on the existence of PARP12. Our findings have broadened the understanding of the anti-viral function of PARP11, and more importantly suggest a potential therapeutics target against ZIKV infection.

scholarly journals Clinical Management of Moyamoya Patients

2021 ◽  
Vol 10 (16) ◽  
pp. 3628
Author(s):  
Isabella Canavero ◽  
Ignazio Gaspare Vetrano ◽  
Marialuisa Zedde ◽  
Rosario Pascarella ◽  
Laura Gatti ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Long Term Outcomes ◽  
Hemorrhagic Risk ◽  
Collateral Vessels ◽  
Hereditary Conditions ◽  
The Brain ◽  
Internal Carotid Arteries

Moyamoya angiopathy (MMA) is a peculiar cerebrovascular condition characterized by progressive steno-occlusion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the development of a network of fragile collateral vessels at the base of the brain. The diagnosis is essentially made by radiological angiographic techniques. MMA is often idiopathic (moyamoya disease-MMD); conversely, it can be associated with acquired or hereditary conditions (moyamoya Syndrome-MMS); however, the pathophysiology underlying either MMD or MMS has not been fully elucidated to date, and this poor knowledge reflects uncertainties and heterogeneity in patient management. MMD and MMS also have similar clinical expressions, including, above all, ischemic and hemorrhagic strokes, then headaches, seizures, cognitive impairment, and movement disorders. The available treatment strategies are currently shared between idiopathic MMD and MMS, including pharmacological and surgical stroke prevention treatments and symptomatic drugs. No pharmacological treatment able to reverse the progressive disappearance of the ICAs has been found to date in both idiopathic and syndromic cases. Antithrombotic agents are usually prescribed in ischemic MMA, although the coexisting hemorrhagic risk should be considered. Surgical revascularization techniques, which are currently the best available treatment in symptomatic MMA, are associated with good long-term outcomes and reduced ischemic and hemorrhagic risks. Given the lack of dedicated randomized clinical trials, current treatment is mainly based on observational studies and physicians’ and surgeons’ expertise.

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