Characterization of Astrocytes in the Minocycline-Administered Mouse Photothrombotic Ischemic Stroke Model

Kondo, Mari; Okazaki, Haruka; Nakayama, Kei Ichi; Hitomi, Hirofumi; Nakagawa, Kimie; Segi-Nishida, Eri; Hasegawa, Hiroshi

doi:10.1007/s11064-022-03703-z

Cited by 11 publications

(8 citation statements)

References 83 publications

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“…Within this context, several investigations have documented that neuronal ischemia increases the expression of TNFα as early as 1 h after the onset of ischemia in the MCAO model [74,75]. Furthermore, Kondo et al and Meng et al demonstrated that the expression of TNFα in cells other than neurons (i.e., microglia and astrocytes) becomes visible more than 24 h after the onset of a stroke [37,76]. Considering that inflammatory processes stimulate neuroprotective effects if they persist for a short time but cause neurodegenerative processes if they persist for a longer time [28], we also examined the time course of TNFα expression in neurons located in the peri-stroke tissue.…”

Section: Discussionmentioning

confidence: 99%

“…TNFα is produced by various cell types, including neurons, microglia, astrocytes, and endothelial cells [28,36]. Previous studies have indicated that the prompt induction of TNFα mRNA in the photothrombotic model likely originates from ischemic neurons and not from activated glial cells [37]. In addition, TNFα is one of the earliest cytokines to appear in the context of the inflammatory reaction after ischemic brain injury, contributing to the stimulation of the inflammatory process in the cerebrospinal fluid and blood serum [38,39].…”

Section: Introductionmentioning

confidence: 99%

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After Ischemic Stroke, Minocycline Promotes a Protective Response in Neurons via the RNA-Binding Protein HuR, with a Positive Impact on Motor Performance

Pawletko

Jędrzejowska–Szypułka

Bogus

et al. 2023

IJMS

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Ischemic stroke is the most common cause of adult disability and one of the leading causes of death worldwide, with a serious socio-economic impact. In the present work, we used a new thromboembolic model, recently developed in our lab, to induce focal cerebral ischemic (FCI) stroke in rats without reperfusion. We analyzed selected proteins implicated in the inflammatory response (such as the RNA-binding protein HuR, TNFα, and HSP70) via immunohistochemistry and western blotting techniques. The main goal of the study was to evaluate the beneficial effects of a single administration of minocycline at a low dose (1 mg/kg intravenously administered 10 min after FCI) on the neurons localized in the penumbra area after an ischemic stroke. Furthermore, given the importance of understanding the crosstalk between molecular parameters and motor functions following FCI, motor tests were also performed, such as the Horizontal Runway Elevated test, CatWalk™ XT, and Grip Strength test. Our results indicate that a single administration of a low dose of minocycline increased the viability of neurons and reduced the neurodegeneration caused by ischemia, resulting in a significant reduction in the infarct volume. At the molecular level, minocycline resulted in a reduction in TNFα content coupled with an increase in the levels of both HSP70 and HuR proteins in the penumbra area. Considering that both HSP70 and TNF-α transcripts are targeted by HuR, the obtained results suggest that, following FCI, this RNA-binding protein promotes a protective response by shifting its binding towards HSP70 instead of TNF-α. Most importantly, motor tests showed that reduced inflammation in the brain damaged area after minocycline treatment directly translated into a better motor performance, which is a fundamental outcome when searching for new therapeutic options for clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

After Ischemic Stroke, Minocycline Promotes a Protective Response in Neurons via the RNA-Binding Protein HuR, with a Positive Impact on Motor Performance

Pawletko

Jędrzejowska–Szypułka

Bogus

et al. 2023

IJMS

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“…Then, in order to quantify the functional integrity of the whole-brain network, voxel-based FCS analysis was further performed. 31 For a given GM voxel, i , we computed its FCS using the following equation:…”

Section: Methodsmentioning

confidence: 99%

Long-range connections damage in white matter hyperintensities affects information processing speed

Lu,

Wang,

Zhu

et al. 2023

Brain Communications

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White matter hyperintensities, one of the major markers of cerebral small vessel disease, disrupt the integrity of neuronal networks and ultimately contribute to cognitive dysfunction. However, a deeper understanding of how white matter hyperintensities related to connectivity patterns of brain hubs at the neural network level could provide valuable insights into the relationship between white matter hyperintensities and cognitive dysfunction. A total of 36 patients with moderate to severe white matter hyperintensities (Fazekas score ≥ 3) and 34 healthy controls underwent comprehensive neuropsychological assessments and resting-state functional-MRI scans. The voxel-based graph-theory approach-functional connectivity strength was employed to systematically investigate the topological organization of the whole-brain networks. The white matter hyperintensities patients performed significantly worse than the healthy controls in episodic memory, executive function, and information processing speed. Additionally, we found that white matter hyperintensities selectively affected highly connected hub regions, predominantly involving the medial and lateral prefrontal, precuneus, inferior parietal lobule, insula, and thalamus. Intriguingly, this impairment was connectivity distance-dependent, with the most prominent disruptions observed in long-range connections (e.g., 100 - 150 mm). Finally, these disruptions of hub connectivity (e.g., the long-range functional connectivity strength in the left dorsolateral prefrontal cortex) positively correlated with the cognitive performance in white matter hyperintensities patients. Our findings emphasize that the disrupted hub connectivity patterns in white matter hyperintensities are dependent on connection distance, especially longer distance connections, which in turn predispose white matter hyperintensities patients to worse cognitive function.

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“…The thymus was fixed in 4% paraformaldehyde in PBS at 4°C for 6 h. Immunohistochemistry was performed as described in our previous study with minor modifications. 10) The paraformaldehyde-fixed thymus tissues were cryoprotected in 30% sucrose in PBS at 4°C overnight. Furthermore, 30-μm-thick sections were prepared using a cryostat (SLEE medical GmbH, Mainz, Germany).…”

Section: Histological Analysesmentioning

confidence: 99%

Different Properties of Involuted Thymus upon Nutritional Deficiency in Young and Aged Mice

Nakayama

Kondo

Okuno

et al. 2023

Biological & Pharmaceutical Bulletin

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Immune suppression in elderly individuals is one of the most important hygienic problems in aged societies. The primary immune organ thymus is histologically and functionally reduced by aging, which is known as thymic involution. The thymus is also involuted by nutritional deficiency, which frequently occurs in elderly individuals. However, there is no information on the thymic changes caused by nutritional deficiency with aging. Therefore, this study was conducted to examine the histological and molecular responses of the thymus to nutritional deficiency in young and aged mice.The thymic size was significantly smaller in 16-or 18-week-old aged mice than in 7-week-old young mice. Dietary restriction for 48 h reduced the thymic size in young mice, but not in aged mice.Immunostaining with anti-keratin 5 antibody revealed that the integrity of the corticomedullary boundary was maintained in the aged thymus, whereas dietary restriction induced its disorganization in both young and aged thymus. The numbers of IgG-positive cells were increased upon dietary restriction in aged, but not in young, thymus. Dietary restriction, but not aging, upregulated the mRNA levels of Th2-related Il5, Il6, and Il10, whereas aging increased that of Th1-related Ifng. The dietary restriction-induced upregulation of prostanoid-synthesizing enzymes was clearly observed in the young thymus but attenuated in the aged thymus. Thus, nutritional deficiency and aging cause an involuted thymus with different properties. Moreover, the thymus in aged mice does not show further reduction in size by nutritional deficiency but still responds differently compared with that in young mice.

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Characterization of Astrocytes in the Minocycline-Administered Mouse Photothrombotic Ischemic Stroke Model

Cited by 11 publications

References 83 publications

After Ischemic Stroke, Minocycline Promotes a Protective Response in Neurons via the RNA-Binding Protein HuR, with a Positive Impact on Motor Performance

After Ischemic Stroke, Minocycline Promotes a Protective Response in Neurons via the RNA-Binding Protein HuR, with a Positive Impact on Motor Performance

Long-range connections damage in white matter hyperintensities affects information processing speed

Different Properties of Involuted Thymus upon Nutritional Deficiency in Young and Aged Mice

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