Proinflammatory cytokines correlate with early exercise attenuating anxiety‐like behavior after cerebral ischemia

Zhang, Qi; Zhang, Jingjun; Yan, Yuzhong; Zhang, Pengyue; Zhang, Wei; Xiao, Rong

doi:10.1002/brb3.854

Cited by 28 publications

(17 citation statements)

References 25 publications

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“…Proliferation and activation of microglia is a key feature in neurodegenerative disease settings [28]. Our data showing microglia activation following anesthesia and surgery are in line with several studies [29][30][31]. Leakage of peripheral cytokines through blood-brain barrier breakdown might be the main trigger [2].…”

Section: Discussionsupporting

confidence: 88%

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

Sun¹,

Wang²,

Ye³

et al. 2021

Preprint

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BackgroundPostoperative cognitive dysfunction (POCD) is a debilitating neurological complication in surgical patients. Current studies mainly focus on microglia activation, however, less is known about the mechanism underlying neuronal synaptic changes involved in microglia activation. Recent studies indicate that silent information regulator 1 (SIRT1) plays critical roles in different neurological disorders, and is involved in microglia activation. Herein, we evaluated the effects of SIRT1 activation on POCD.MethodsExploratory laparotomy were employed on mice (12-14 month) under sevoflurane anesthesia to establish model of POCD. Transcriptional changes in hippocampus after anesthesia and surgery were evaluated by RNA sequencing. SIRT1 expression were verified by Western Blot. Mice were treated with SIRT1 agonist SRT1720 or vehicle after surgery. Changes in microglia morphology, microglial phagocytosis, as well as dystrophic neurites and dendritic spine density were determined. Cognitive functions were evaluated by Y maze and Morris water maze.ResultsSIRT1 expression levels were downregulated in anesthesia and surgery group. Anesthesia and surgery lead to microglia morphology alteration, enhanced synaptic engulfment, dendritic spine loss, and cognitive deficits in our mice model, all of which were alleviated by SRT1720 administration.ConclusionOur study unveils one of the roles of SIRT1 in POCD pathogenesis. SIRT1 activation may represent a therapeutic strategy for prevention and treatment of POCD.

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Section: Discussionsupporting

confidence: 88%

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

Sun¹,

Wang²,

Ye³

et al. 2021

Preprint

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“…The therapeutic doses of physical exercise training used in our study were calculated as 40% of this maximum velocity for mild exercise training, which amounted to approximately 15 m/min, and 80% of the maximum velocity for intense exercise training, which was about 32 m/min (Zhang et al, 2012 ; Li F. et al, 2020 ). To further accentuate the difference between the two categories, we reduced the mild exercise group’s speed to a maximum of 12 m/min as done by previous studies (Tian et al, 2013 ; Zhang et al, 2017 ; Tang et al, 2018 ; Li F. et al, 2020 ). For the high-intensity group, we selected 30 m/min because we have employed this speed in our previous work, in which we found that it reduced brain damage (Ding et al, 2006 ), blood-brain barrier dysfunction (Guo et al, 2008 ), and brain inflammation in stroke (Curry et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Effects of Exercise Postconditioning After Stroke via SIRT1-Mediated Suppression of Endoplasmic Reticulum (ER) Stress

Lee

et al. 2021

Front. Cell. Neurosci.

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While it is well-known that pre-stroke exercise conditioning reduces the incidence of stroke and the development of comorbidities, it is unclear whether post-stroke exercise conditioning is also neuroprotective. The present study investigated whether exercise postconditioning (PostE) induced neuroprotection and elucidated the involvement of SIRT1 regulation on the ROS/ER stress pathway. Adult rats were subjected to middle cerebral artery occlusion (MCAO) followed by either: (1) resting; (2) mild exercise postconditioning (MPostE); or (3) intense exercise postconditioning (IPostE). PostE was initiated 24 h after reperfusion and performed on a treadmill. At 1 and 3 days thereafter, we determined infarct volumes, neurological defects, brain edema, apoptotic cell death through measuring pro- (BAX and Caspase-3) and anti-apoptotic (Bcl-2) proteins, and ER stress through the measurement of glucose-regulated protein 78 (GRP78), inositol-requiring 1α (IRE1α), protein kinase RNA-like endoplasmic reticulum kinase (PERK), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), Caspase-12, and SIRT1. Proteins were measured by Western blot. ROS production was detected by flow cytometry.Compared to resting rats, both MPostE and IPostE significantly decreased brain infarct volumes and edema, neurological deficits, ROS production, and apoptotic cell death. MPostE further increased Bcl-2 expression and Bcl-2/BAX ratio as well as BAX and Caspase-3 expressions and ROS production (*p < 0.05). Both PostE groups saw decreases in ER stress proteins, while MPostE demonstrated a further reduction in GRP78 (***p < 0.001) and Caspase-12 (*p < 0.05) expressions at 1 day and IRE1α (**p < 0.01) and CHOP (*p < 0.05) expressions at 3 days. Additionally, both PostE groups saw significant increases in SIRT1 expression.In this study, both mild and intense PostE levels induced neuroprotection after stroke through SIRT1 and ROS/ER stress pathway. Additionally, the results may provide a base for our future study regarding the regulation of SIRT1 on the ROS/ER stress pathway in the biochemical processes underlying post-stroke neuroprotection. The results suggest that mild exercise postconditioning might play a similar neuroprotective role as intensive exercise and could be an effective exercise strategy as well.

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“…The therapeutic doses of physical exercise training used in our study were calculated as 40% of this maximum velocity in the case of mild exercise training, which amounted to approximately 15 m/min, and 80% in the case of intense exercise training, which was about 32 m/min (Zhang et al, 2012 ). To further increase the difference between our categories, we reduced speed in the mild group to a maximum of 12 m/min as previous studies (Tian et al, 2013 ; Zhang P. et al, 2013 ; Zhang et al, 2017 ; Tang et al, 2018 ). For the high-intensity group, we selected 30 m/min because we have employed this speed in previous work, in which we found that it reduced brain damage (Ding et al, 2006 ), blood-brain barrier dysfunction (Guo et al, 2008 ), and brain inflammation in stroke (Curry et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

Huber

et al. 2020

Front. Cell. Neurosci.

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Although physical exercise has been demonstrated to augment recovery of the post-stroke brain, the question of what level of exercise intensity optimizes neurological outcomes of post-stroke rehabilitation remains unsettled. In this study, we aim to clarify the mechanisms underlying the intensity-dependent effect of exercise on neurologic function, and thereby to help direct the clinical application of exercisebased neurorehabilitation. To do this, we used a well-established rat model of ischemic stroke consisting of cerebral ischemia induction through middle cerebral artery occlusion (MCAO). Ischemic rats were subsequently assigned either to a control group entailing post-stroke rest or to one of two exercise groups distinguished by the intensity of their accompanying treadmill regimens. After 24 h of reperfusion, exercise was initiated. Infarct volume, apoptotic cell death, and neurological defects were quantified in all groups at 3 days, and motor and cognitive functions were tracked up to day-28. Additionally, Western blotting was used to assess the influence of our interventions on several proteins related to synaptogenesis and neuroplasticity (growth-associated protein 43, a microtubule-associated protein, postsynaptic density-95, synapsin I, hypoxia-inducible factor-1α, brain-derived neurotrophic factor, nerve growth factor, tyrosine kinase B, and cAMP response element-binding protein). Our results were in equal parts encouraging and surprising. Both mild and intense exercise significantly decreased infarct volume, cell death, and neurological deficits. Motor and cognitive function, as determined using an array of tests such as beam balance, forelimb placing, and the Morris water maze, were also significantly improved by both exercise protocols. Interestingly, while an obvious enhancement of neuroplasticity proteins was shown in both exercise groups, mild exercise rats demonstrated a stronger effect on the expressions of Tau (p < 0.01), brain-derived neurotrophic factor (p < 0.01), and tyrosine kinase B (p < 0.05). These findings contribute to the growing body of literature regarding the positive effects of both mild and intense long-term treadmill exercise on brain injury, functional outcome, and

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Proinflammatory cytokines correlate with early exercise attenuating anxiety‐like behavior after cerebral ischemia

Cited by 28 publications

References 25 publications

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

SIRT1 Activation Attenuates Microglia Mediated Synaptic Engulfment in Postoperative Cognitive Dysfunction

Neuroprotective Effects of Exercise Postconditioning After Stroke via SIRT1-Mediated Suppression of Endoplasmic Reticulum (ER) Stress

In Search of a Dose: The Functional and Molecular Effects of Exercise on Post-stroke Rehabilitation in Rats

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