Local fractal dimension of collagen detects increased spatial complexity in fibrosis

Introduction: 2,4-dichlorophenoxyacetic acid (2,4-D) is one of the most used in the world and exposure to herbicides can affect animals and humans, causing toxic effects that include cardiotoxicity. This is the first study to evaluate cardiac remodeling after experimental simulation of environmental exposure by chronic inhalation (6 months) to the herbicide 2,4-D. Methods: Thirty male Wistar rats were exposed to two different concentrations of the 2,4-D formulation (low – 187.17 mg/m3; and high – 467.93 mg/m3) and the control group exposed to nebulization of chloride solution 0.9% sodium. Inhalation exposure lasted 6 months. Mice hearts were collected for histology. Results: There was a difference between exposure concentrations in relation to the increase in cardiac collagen (P < 0.0001). In mice exposed to a low dose of 2,4-D and a decrease in the fractal dimension of cardiac collagen in the high dose of 2, 4-D (P = 0.010). Discussion: This study shows that chronic inhalation exposure to 2,4-D induces cardiotoxicity in rats, characterized by extracellular matrix reorganization and changes in collagen levels, highlighting the impact of the exposure route on cardiac outcomes. Conclusion: There was no difference in relation to anatomical parameters, cardiomyocyte area, collagen types I and III and analysis of arteriole thickness. Chronic exposure at different doses to the 2,4D herbicide had the potential to cause damage to cardiac remodeling by altering cardiac collagen in rats.

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Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia

Ardaya,

Tiveron,

Cremer

et al. 2023

Preprint

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Activation of the subventricular zone (SVZ) after cerebral ischemia is one of the early responses in the brain to counteract the loss of neurons and reduce tissue damage. Impaired brain regions communicate with the SVZ through many chemotactic messages that result in neural stem cells (NSC) migration and differentiation. However, the activation of gliogenesis and the role of newborn astrocytes in the post-ischemic scenario is still under debate. We have previously shown that adenosine release after brain ischemia prompts the SVZ to generate new astrocytes. Here, we use transient brain ischemia in mice to define the cellular origin of these astrocytes in the SVZ neurogenic niche and investigate their role in the pathological process. By combining immunofluorescence, BrdU-tracing and genetic cellular labelling, we tracked the migration of newborn astrocytes, positive for the proteoglycan marker Thbs4, from the dorsal and medial SVZ to the glial scar surrounding the ischemic core. We found that these Thbs4-positive astrocytes modulate the dense extracellular matrix at the scar by synthesis but also degradation of hyaluronan. We also show that while the accumulation of this polymer at the scar is sufficient to recruit newborn astrocytes, its degradation at the SVZ correlates with gliogenesis. These results point to newborn astrocytes as a plausible pharmacological target to modulate the glial scar after brain ischemia and facilitate tissue regeneration.

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Local fractal dimension of collagen detects increased spatial complexity in fibrosis

Cited by 6 publications

References 43 publications

Complex shape markers can detect alterations in the spatial distribution of cell nuclei in human lung squamous cell carcinoma: a useful tool for automatic analysis?

Complex shape markers can detect alterations in the spatial distribution of cell nuclei in human lung squamous cell carcinoma: a useful tool for automatic analysis?

Chronic inhalation exposure to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) alters cardiac collagen in Wistar rats

Gliogenesis from the subventricular zone modulates the extracellular matrix at the glial scar after brain ischemia

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