Microglial Inflammation and Cognitive Dysfunction in Comorbid Rat Models of Striatal Ischemic Stroke and Alzheimer’s Disease: Effects of Antioxidant Catalase-SKL on Behavioral and Cellular Pathology

MacKenzie, Jennifer L.; Ivanova, N. A.; Nell, Hayley J.; Giordano, Courtney R.; Terlecky, Stanley R.; Ağca, Cansu; Ağca, Yüksel; Walton, Paul A.; Whitehead, Shawn N.; Cechetto, David F.

doi:10.1016/j.neuroscience.2022.01.026

Cited by 8 publications

(4 citation statements)

References 101 publications

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“…Similarly, since we predicted a decrease in stroke-related pathology in the striatum of minocycline-treated rats, we also hypothesized that there would be an improvement in striatal-based learning. Although previous experimental studies using minocycline have observed improvements in hippocampal-based tasks [39][40][41] , similar stroke models to ours have not reported hippocampal de cits 43,44 , thus we did not expect to see treatment differences in this cognitive domain. To address these hypotheses, we administered 4 days of minocycline treatment post-unilateral focal subcortical stroke and assessed its effect on chronic microglia and astrocyte expression in the infarct and remote brain regions and various domains of cognitive function.…”

Section: Introductionmentioning

confidence: 40%

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-stroke cognition in rats

Myers

Agapova

Patel

et al. 2023

Preprint

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Ischemic stroke affects millions of individuals worldwide and a high prevalence of survivors experience cognitive deficits. At present, the underlying mechanisms that drive post-stroke cognitive decline are not well understood. Microglia play a critical role in the post-stroke inflammatory response, but experimental studies show that an accumulation of chronically activated microglia can be harmful and associates with cognitive impairment. This study aimed to assess the effect of acute post-stroke minocycline treatment, a tetracycline derivative that readily crosses the blood-brain barrier and has been shown to inhibit microglia activation, on chronic microglia and astrocyte expression within both the infarct and remote white matter regions, as well as determine its effect on various domains of cognitive function post-stroke. Nine-month-old male rats received an injection of endothelin-1 into the right dorsal striatum to induce a transient focal ischemic stroke, and then were treated with minocycline or saline for 4 days post-stroke. Rats were tested using a series of lever-pressing tasks and the Morris water maze to assess striatal-based learning, cognitive flexibility, and spatial learning and reference memory. We found that minocycline-treated rats had smaller stroke-induced infarcts, less microglia activation in the infarct area and less microglia activation in remote white matter regions compared to saline-treated rats at 28 days post-stroke. The behavioural testing results differed according to the cognitive domain; whereas minocycline-treated rats trended towards improved striatal-based learning in a lever-pressing task, but cognitive flexibility was unaffected during the subsequent set-shifting task. Furthermore, minocycline treatment unexpectedly impaired spatial learning, yet it did not alter reference memory. Collectively, we show that post-stroke minocycline treatment can reduce chronic microglia activation even in remote brain regions, with domain-specific effects on cognitive function.

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Section: Introductionmentioning

confidence: 40%

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-stroke cognition in rats

Myers

Agapova

Patel

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similarly, since we predicted a decrease in stroke-related pathology in the striatum of minocycline-treated rats, we also hypothesized that there would be an improvement in striatal-based learning. Although previous experimental studies using minocycline have observed improvements in hippocampal-based tasks [40][41][42], similar stroke models to ours have not reported hippocampal de cits [44,45], thus we did not expect to see treatment differences in this cognitive domain. In the present study, we administered 4 days of minocycline treatment post-unilateral focal subcortical stroke and used immunohistochemistry to assess its effect on infarct volume and chronic microglia and astrocyte expression in both the infarct and remote brain regions.…”

Section: Introductionmentioning

confidence: 40%

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-ischemic stroke cognition in rats

Myers,

Agapova,

Patel

et al. 2023

Behavioural Brain Research

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“…The lack of this enzyme, or the presence of its mutation, has been observed to be in direct correlation with several neurodegenerative disorders [ 77 ]. Catalase treatment was reported to ameliorate memory deficit in AD [ 84 ], attenuate neurotoxicity and neuroinflammation [ 85 ], and provide significant neuroprotective effects in PD [ 86 ].…”

Section: Neuroprotection and Antioxidantsmentioning

confidence: 99%

An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases

Teleanu

Niculescu

Lungu

et al. 2022

IJMS

380

139

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Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress of several neurodegenerative disorders. This review intends to summarize some of the findings that correlate the overproduction of reactive oxygen species with the pathophysiology of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Oxidative stress was also noted to modify the inflammatory response. Even though oxidative stress and neuroinflammation are two totally different pathological events, they are linked and affect one another. Nonetheless, there are still several mechanisms that need to be understood regarding the onset and the progress of neurodegenerative diseases in order to develop efficient therapies. As antioxidants are a means to alter oxidative stress and slow down the symptoms of these neurodegenerative diseases, the most common antioxidants, enzymatic as well as non-enzymatic, have been mentioned in this paper as therapeutic options for the discussed disorders.

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Microglial Inflammation and Cognitive Dysfunction in Comorbid Rat Models of Striatal Ischemic Stroke and Alzheimer’s Disease: Effects of Antioxidant Catalase-SKL on Behavioral and Cellular Pathology

Cited by 8 publications

References 101 publications

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-stroke cognition in rats

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-stroke cognition in rats

Acute minocycline treatment inhibits microglia activation, reduces infarct volume, and has domain-specific effects on post-ischemic stroke cognition in rats

An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases

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