Role of DAMPs and of Leukocytes Infiltration in Ischemic Stroke: Insights from Animal Models and Translation to the Human Disease

Thiourea and dimethylthiourea are powerful scavengers of hydroxyl radicals (.OH), and dimethylthiourea has been used to test the involvement of .OH in several animal models of human disease. It is shown that both thiourea and dimethylthiourea are scavengers of HOCl, a powerful oxidant produced by neutrophil myeloperoxidase. Hence the ability of dimethylthiourea to protect against neutrophil-mediated tissue damage cannot be used as evidence for a role of .OH in causing such damage. Dimethyl sulphoxide also reacts with HOCl, but at a rate that is probably too low to be biologically significant at dimethyl sulphoxide concentrations up to 10 mM. Neither mannitol nor desferrioxamine, at the concentrations normally used in radical-generating systems, appears to react with HOCl.

Download Full-text

Preclinical and clinical evidence of IGF-1 as a prognostic marker and acute intervention with ischemic stroke

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x211000894 ◽

2021 ◽

pp. 0271678X2110008

Author(s):

Cellas A Hayes ◽

M Noa Valcarcel-Ares ◽

Nicole M Ashpole

Keyword(s):

Ischemic Stroke ◽

Animal Models ◽

The Elderly ◽

Clinical Settings ◽

Mortality And Morbidity ◽

Routes Of Administration ◽

Insulin Growth Factor ◽

Cellular Processes ◽

Preclinical Animal Models

Ischemic strokes are highly prevalent in the elderly population and are a leading cause of mortality and morbidity worldwide. The risk of ischemic stroke increases in advanced age, corresponding with a noted decrease in circulating insulin growth factor-1 (IGF-1). IGF-1 is a known neuroprotectant involved in embryonic development, neurogenesis, neurotransmission, cognition, and lifespan. Clinically, several studies have shown that reduced levels of IGF-1 correlate with increased mortality rate, poorer functional outcomes, and increased morbidities following an ischemic stroke. In animal models of ischemia, administering exogenous IGF-1 using various routes of administration (intranasal, intravenous, subcutaneous, or topical) at various time points prior to and following insult attenuates neurological damage and accompanying behavioral changes caused by ischemia. However, there are some contrasting findings in select clinical and preclinical studies. This review discusses the role of IGF-1 as a determinant factor of ischemic stroke outcomes, both within the clinical settings and preclinical animal models. Furthermore, the review provides insight on the role of IGF-1 in mechanisms and cellular processes that contribute to stroke damage.

Download Full-text

The role of disturbed blood flow in the development of pulmonary arterial hypertension: lessons from preclinical animal models

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00031.2013 ◽

2013 ◽

Vol 305 (1) ◽

pp. L1-L14 ◽

Cited By ~ 45

Author(s):

Michael G. Dickinson ◽

Beatrijs Bartelds ◽

Marinus A. J. Borgdorff ◽

Rolf M. F. Berger

Keyword(s):

Blood Flow ◽

Pulmonary Arterial Hypertension ◽

Animal Models ◽

Arterial Hypertension ◽

Human Disease ◽

Vascular Remodeling ◽

Pulmonary Blood Flow ◽

Current Knowledge ◽

Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive pulmonary vasoproliferative disorder characterized by the development of unique neointimal lesions, including concentric laminar intima fibrosis and plexiform lesions. Although the histomorphology of neointimal lesions is well described, the pathogenesis of PAH and neointimal development is largely unknown. After three decades of PAH pathobiology research the focus has shifted from vasoconstriction towards a mechanism of cancer-like angioproliferation. In this concept the role of disturbed blood flow is seen as an important trigger in the development of vascular remodeling. For instance, in PAH associated with congenital heart disease, increased pulmonary blood flow (i.e., systemic-to-pulmonary shunt) is an essential trigger for the occurrence of neointimal lesions and PAH development. Still, questions remain about the exact role of these blood flow characteristics in disease progression. PAH animal models are important for obtaining insight in new pathobiological processes and therapeutical targets. However, as for any preclinical model the pathophysiological mechanism and clinical course has to be comparable to the human disease that it mimics. This means that animal models mimicking human PAH ideally are characterized by: a hit recognized in human disease (e.g., altered pulmonary blood flow), specific vascular remodeling resembling human neointimal lesions, and disease progression that leads to right ventriclular dysfunction and death. A review that underlines the current knowledge of PAH due to disturbed flow is still lacking. In this review we will summarize the current knowledge obtained from PAH animal models associated with disturbed pulmonary blood flow and address questions for future treatment strategies for PAH.

Download Full-text

The role of cytokines and pathogen recognition molecules in fungal keratitis – Insights from human disease and animal models

Cytokine ◽

10.1016/j.cyto.2011.12.022 ◽

2012 ◽

Vol 58 (1) ◽

pp. 107-111 ◽

Cited By ~ 27

Author(s):

Sixto M. Leal ◽

Eric Pearlman

Keyword(s):

Animal Models ◽

Human Disease ◽

Fungal Keratitis ◽

Pathogen Recognition

Download Full-text

Animal Models of Peripheral Neuropathy and Neuropathic Pain

10.1093/med/9780199937837.003.0119 ◽

2017 ◽

Author(s):

Katelyn Donaldson ◽

Ahmet Höke

Keyword(s):

Neuropathic Pain ◽

Peripheral Neuropathy ◽

Animal Models ◽

Human Disease ◽

New Drugs ◽

Molecular Pathways ◽

Peripheral Neuropathies ◽

Different Types

There are numerous types of peripheral neuropathies and conditions that cause neuropathic pain with varying symptoms and different mechanisms of pathogenesis. Therefore, it is not surprising that many different animal models of peripheral neuropathies and neuropathic pain have been developed with varying degrees of fidelity to recapitulate the human disease. Nevertheless, these models are useful in a deconstructive manner to examine role of specific molecular pathways in pathogenesis of different types of peripheral neuropathies and test potential new drugs.

Download Full-text

Animal Models of CNS Viral Disease: Examples from Borna Disease Virus Models

Interdisciplinary Perspectives on Infectious Diseases ◽

10.1155/2010/709791 ◽

2010 ◽

Vol 2010 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Marylou V. Solbrig

Keyword(s):

Animal Models ◽

Disease Virus ◽

Human Disease ◽

Rna Virus ◽

Bird Species ◽

Viral Disease ◽

Borna Disease Virus ◽

Neuropsychiatric Diseases ◽

Borna Disease

Borna disease (BD), caused by the neurotropic RNA virus, Borna Disease virus, is an affliction ranging from asymptomatic to fatal meningoencephalitis across naturally and experimentally infected warmblooded (mammalian and bird) species. More than 100 years after the first clinical descriptions of Borna disease in horses and studies beginning in the 1980's linking Borna disease virus to human neuropsychiatric diseases, experimentally infected rodents have been used as models for examining behavioral, neuropharmacological, and neurochemical responses to viral challenge at different stages of life. These studies have contributed to understanding the role of CNS viral injury in vulnerability to behavioral, developmental, epileptic, and neurodegenerative diseases and aided evaluation of the proposed and still controversial links to human disease.

Download Full-text