scholarly journals Selective intra-arterial brain cooling improves long-term outcomes in a non-human primate model of embolic stroke: Efficacy depending on reperfusion status

2020 ◽  
Vol 40 (7) ◽  
pp. 1415-1426 ◽  
Author(s):  
Di Wu ◽  
Jian Chen ◽  
Mohammed Hussain ◽  
Longfei Wu ◽  
Jingfei Shi ◽  
...  
Keyword(s):  
Rhesus Macaques ◽  
Motor Dysfunction ◽  
Neurological Deficits ◽  
Brain Cooling ◽  
Long Term Outcomes ◽  
Primate Model ◽  
Tissue Plasminogen ◽  
Human Primate ◽  
Arterial Thrombolysis

Nearly all stroke neuroprotection modalities, including selective intra-arterial cooling (SI-AC), have failed to be translated from bench to bed side. Potentially overlooked reasons may be biological gaps, inadequate attention to reperfusion states and mismatched attention to neurological benefits. To advance stroke translation, we describe a novel thrombus-based stroke model in adult rhesus macaques. Intra-arterial thrombolysis with tissue plasminogen activator leads to three clinically relevant outcomes – complete, partial, and no recanalization based on digital subtraction angiography. We also find reperfusion as a prerequisite for SI-AC-induced benefits, in which models with complete or partial reperfusion exhibit significantly reduced infarct volumes, mitigated neurological deficits, improved upper limb motor dysfunction in both acute and chronic stages; however, no further neuroprotection is observed in those without reperfusion. In summary, we discover reperfusion as a crucial regulator of SI-AC-induced neuroprotection and provide insights of long-term functional benefits in behavior and imaging levels. Our findings could be important not only for the translational prerequisite and potential molecular targets, but also for this thrombus-thrombolysis model in monkeys as a powerful tool for further translational stroke studies.

Endovascular management of acute ischemic stroke

2009 ◽  
Vol 26 (3) ◽  
pp. E2 ◽  
Author(s):  
Chirag D. Gandhi ◽  
Lana D. Christiano ◽  
Charles J. Prestigiacomo
Keyword(s):  
Acute Stroke ◽  
Plasminogen Activator ◽  
Tissue Plasminogen Activator ◽  
Treatment Options ◽  
Antiplatelet Agents ◽  
Interventional Treatment ◽  
Long Term Outcomes ◽  
Treatment Protocols ◽  
Tissue Plasminogen

The management of stroke has progressed significantly over the past 2 decades due to successful treatment protocols including intravenous and intraarterial options. The intravenous administration of tissue plasminogen activator within an established treatment window has been proven in large, well-designed studies. The evolution of endovascular strategies for acute stroke has been prompted by the limits of the intravenous treatment, as well as by the desire to demonstrate improved recanalization rates and improved long-term outcomes. The interventional treatment options available today are the intraarterial administration of tissue plasminogen activator and newer antiplatelet agents, mechanical thrombectomy with the MERCI device and the Penumbra system, and intracranial angioplasty and stent placement. In this review the authors outline the major studies that have defined the current field of acute stroke management and discuss the basic treatment paradigms that are commonly used today.

scholarly journals Infant Rhesus Macaques as a Nonhuman Primate Model of Bordetella Pertussis

2020 ◽  
Author(s):  
Li Shi ◽  
Wenwen Jiang ◽  
Chen Wei ◽  
Dachao Mou ◽  
Weilun Zuo ◽  
...  
Keyword(s):  
Animal Model ◽  
Bordetella Pertussis ◽  
Whooping Cough ◽  
Rhesus Macaques ◽  
Public Health Problem ◽  
Primate Model ◽  
Pertussis Infection ◽  
Cellular Immune ◽  
Infant Rhesus ◽  
Human Primate

Abstract Background: The prevalent resurgence of pertussis recently creates a vital public health problem worldwide. To understand the pertussis pathogenesis and host response to both pathogen and vaccine, a suitable pertussis animal model, particularly a non-human primate model, is necessary. Recently, a successful non-human primate pertussis model of baboons have been established. However, though the rhesus macaques have been proven to be ideal animal models for several infectious diseases, the infectious model of pertussis has not been established on it. The previous studies on rhesus macaque models of pertussis were performed in 1920s-1930s with limited experimental details. Recent monkey pertussis models failed to be established because the typical clinic syndrome and transmission were not investigated.Methods: In the present study, infant rhesus macaques were challenged with Bordetella pertussis (B.p) using the aerosol method to evaluate the feasibility of using it as an animal model of pertussis infection.Results: Upon aerosol infection, monkeys infected with the recent clinically isolated B.p strain 2016-CY-41 developed typical whooping cough, leukocytosis, bacteria-positive nasopharyngeal wash (NPW), and inter-animal transmission. Both humoral and cellular immune responses were induced by B.pertussis.Conclusion: These results demonstrate that a model of pertussis infection was successfully established in infant rhesus macaques, which provides a valuable platform to study pertussis pathogenesis and evaluate vaccine candidates.

scholarly journals Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

2018 ◽  
Author(s):  
Jonathan O. Rayner ◽  
Raj Kalkeri ◽  
Scott Goebel ◽  
Zhaohui Cai ◽  
Brian Green ◽  
...  
Keyword(s):  
Immune Response ◽  
Zika Virus ◽  
Rhesus Macaques ◽  
New Drugs ◽  
Primate Model ◽  
Robust Immune Response ◽  
African Lineage ◽  
Limit Of Quantitation ◽  
Asian Lineage ◽  
Human Primate

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose dependent peak viral loads between days 2 and 5 post infection; and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assays lower limit of quantitation and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasures development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

scholarly journals Prior dengue immunity enhances Zika virus infection of the maternal-fetal interface in rhesus macaques

2021 ◽  
Author(s):  
C. M. Crooks ◽  
A. M. Weiler ◽  
S. L. Rybarczyk ◽  
M. I. Bliss ◽  
A. S. Jaeger ◽  
...  
Keyword(s):  
Zika Virus ◽  
Rhesus Macaques ◽  
Maternal Plasma ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Primate Model ◽  
Denv Serotypes ◽  
The Impact ◽  
Human Primate ◽  
Maternal Fetal Interface

ABSTRACTConcerns have arisen that pre-existing immunity to dengue virus (DENV) could enhance Zika virus (ZIKV) disease, due to the homology between ZIKV and DENV and the observation of antibody-dependent enhancement (ADE) among DENV serotypes. To date, no study has examined the impact of pre-existing DENV immunity on ZIKV pathogenesis during pregnancy in a translational non-human primate model. Here we show that prior DENV-2 exposure enhanced ZIKV infection of maternal-fetal interface tissues in macaques. However, pre-existing DENV immunity had no detectable impact on ZIKV replication kinetics in maternal plasma, and all pregnancies progressed to term without adverse outcomes or gross fetal abnormalities detectable at delivery. Understanding the risks of ADE to pregnant women worldwide is critical as vaccines against DENV and ZIKV are developed and licensed and as DENV and ZIKV continue to circulate.

scholarly journals Higher Serum-Soluble α-Klotho Level Does Not Predict Longer Survival after Stroke

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Dagmara Adamska-Tomaszewska ◽  
Jarosław Wajda ◽  
Katarzyna Wyskida ◽  
Dawid Bednarczyk ◽  
Maciej Świat ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Fibroblast Growth Factor 23 ◽  
Serum Levels ◽  
Neurological Deficits ◽  
Long Term Outcomes ◽  
Recurrent Strokes ◽  
Klotho Protein ◽  
Aims And Scope

Aims and Scope. Ischemic stroke (IS) is one of the main causes of death and disability worldwide. It has been suggested that the Klotho protein, playing a preventive role in the development of atherosclerosis, may be associated with a better recovery after IS. Therefore, the aim of this study was to analyze whether Klotho serum levels indeed correlate with long-term IS outcomes, such as overall survival (OS) and stroke-free survival (SFS). Material and Methods. The study group consisted of 217 patients with onset of IS symptoms within 24 hours before admission to the hospital. IS was diagnosed using the WHO criteria and radiology imaging. ELISA kits were used to assess soluble α-Klotho and fibroblast growth factor 23 serum levels. Results. There were 5 recurrent strokes and 89 deaths during the 36-month follow-up. Even though no significant differences in OS and SFS between soluble α-Klotho level tertile groups were recorded, unexpectedly, OS and SFS were highest in patients with the lowest soluble α-Klotho concentrations. Moreover, the Cox proportional models adjusted for established risk factors, kidney function, and the severity of stroke revealed that each 100 pg/mL increase in soluble α-Klotho levels was associated with decreased OS ( HR = 0.951 (0.908–0.995), p < 0.05 ) and SFS ( HR = 0.949 (0.908–0.993), p < 0.05 ). In addition, the α-Klotho to iFGF23 index was predicting neither OS nor SFS. Conclusion. Soluble α-Klotho levels in serum were not related to the severity of neurological deficits and long-term outcomes in patients with IS. No neuroprotective effect of soluble α-Klotho levels in patients with IS was demonstrated.

scholarly journals Three-Month and Long-Term Outcomes and Their Predictors in Acute Basilar Artery Occlusion Treated With Intra-Arterial Thrombolysis

Stroke ◽  
2011 ◽  
Vol 42 (7) ◽  
pp. 1946-1951 ◽  
Author(s):  
Simon Jung ◽  
Marie-Luise Mono ◽  
Urs Fischer ◽  
Aekaterini Galimanis ◽  
Oliver Findling ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Artery Occlusion ◽  
Basilar Artery Occlusion ◽  
Long Term Outcomes ◽  
Arterial Thrombolysis

scholarly journals A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

2020 ◽  
pp. 0271678X2092131 ◽  
Author(s):  
Justine Debatisse ◽  
Océane Wateau ◽  
Tae-Hee Cho ◽  
Nicolas Costes ◽  
Inés Mérida ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Fine Motor ◽  
Area At Risk ◽  
Primate Model ◽  
Endovascular Thrombectomy ◽  
Blood Brain Barrier Disruption ◽  
Reperfusion Damage ◽  
Brain Barrier Disruption ◽  
Human Primate

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood–brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia ( Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: “symptomatic salvaged tissue” (SST) and “asymptomatic infarcted tissue” (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia–reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

scholarly journals Failed remyelination of the non-human primate optic nerve leads to axon degeneration, retinal damages and visual dysfunction.

2022 ◽  
Author(s):  
Nadege Sarrazin ◽  
Estelle Chavret-Recculon ◽  
Corinne Bachelin ◽  
Mehdi Felfli ◽  
Rafik Arab ◽  
...  
Keyword(s):  
Optic Nerve ◽  
Axonal Degeneration ◽  
Motor Behavior ◽  
Neuronal Degeneration ◽  
Visual Dysfunction ◽  
Primate Model ◽  
Myelin Disorders ◽  
Therapeutic Avenue ◽  
Human Primate

White matter disorders of the CNS such as MS, lead to failure of nerve conduction and long-lasting neurological disabilities affecting a variety of sensory and motor systems including vision. While most disease-modifying therapies target the immune and inflammatory response, the promotion of remyelination has become a new therapeutic avenue, to prevent neuronal degeneration and promote recovery. Most of these strategies are developed in short-lived rodent models of demyelination, which spontaneously repair and do not reflect the size, organization, and biology of the human CNS. Thus, well-defined non-human primate models are required to efficiently advance therapeutic approaches for patients. Here, we followed the consequence of long-term toxin-induced demyelination of the macaque optic nerve on remyelination and axon preservation, as well as its impact on visual functions. Findings from oculo-motor behavior, ophthalmic examination, electrophysiology, and retinal imaging indicate visual impairment involving the optic nerve and retina. These visual dysfunctions fully correlated at the anatomical level, with sustained optic nerve demyelination, axonal degeneration, and alterations of the inner retinal layers. This non-human primate model of chronic optic nerve demyelination associated with axonal degeneration and visual dysfunction, recapitulates several key features of MS lesions and should be instrumental in providing the missing link to translate emerging repair pro-myelinating/neuroprotective therapies to the clinic for myelin disorders such as MS.

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