Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice

Purpose Ex-PRESS glaucoma shunt stainless steel devices have been used worldwide for glaucoma treatment. The purpose of this study was to evaluate the safety of high-field magnetic resonance imaging (MRI) for Ex-PRESS–inserted eyes. Methods Using rabbits, we performed Ex-PRESS shunt surgery in one eye in each rabbit and divided the rabbits into MRI and non-MRI groups. In the MRI group, 1 week after Ex-PRESS shunt surgery under low specific absorption rate (SAR) conditions and 1 week later under high SAR conditions, high-field 4.7-Tesla MRI was performed. Aqueous flare counts were measured before and after the Ex-PRESS shunt surgery and each MRI examination. The rabbits in the non-MRI group received only general anesthesia, and aqueous flare counts were measured as for those of the MRI group. Aqueous flare counts were expressed in photon counts per millisecond. Results No dislocation of the Ex-PRESS shunt device was observed after MRI. The flare count ratio (MRI/non-MRI) in Ex-PRESS–inserted eyes 2 hours after high SAR MRI increased significantly compared with that before MRI (0.8 ± 0.3 vs 2.7 ± 0.8; pre-high SAR MRI vs 2 hours after high SAR MRI, respectively; P = 0.01). The day after MRI, the flare count improved spontaneously to the same level as that before MRI. Conclusions Our results indicate that high-field MRI can be performed relatively safely after Ex-PRESS shunt surgery. Translational Relevance This study demonstrates the safety of high-field MRI for Ex-PRESS–inserted eyes using a rabbit model.

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“… 27 Additionally, prolonged isoflurane anesthesia has also been reported to produce neuroinflammation. 28 …”

Section: Discussionmentioning

confidence: 99%

Aqueous Flare Changes in Ex-PRESS Glaucoma Shunt Eyes After 4.7 Tesla High-Field Magnetic Resonance Imaging

Edo

Nakamura-Shibasaki

Tamura

et al. 2023

Trans. Vis. Sci. Tech.

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“…Much work has been done to inhibit one of these key cytokines and to reverse A1-like astrocytes, but few have effectively stopped or slowed aging. 71,72 This may be because there are many alternatives to the silenced pathway. Given that astrocyte-driven neuroinflammatory pathways are indeed one of the mechanisms of aging, future research could focus more on how these pathways interact and compensate with each other.…”

Section: Astrocytes: the Impairment Of Neurovascular Unit Homeostasismentioning

confidence: 99%

Alterations of the blood-brain barrier during aging

Cao,

Xu,

Liu

2024

J Cereb Blood Flow Metab

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The blood-brain barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules and cells between the blood and the central nervous system. It undergoes structural and functional changes during aging, which may compromise its integrity and contribute to the pathogenesis of neurodegenerative diseases. In recent years, advances in microscopy and high-throughput bioinformatics have allowed a more in-depth investigation of the aging mechanisms of BBB. This review summarizes age-related alterations of the BBB structure and function from six perspectives: endothelial cells, astrocytes, pericytes, basement membrane, microglia and perivascular macrophages, and fibroblasts, ranging from the molecular level to the human multi-system level. These basic components are essential for the proper functioning of the BBB. Recent imaging methods of BBB were also reviewed. Elucidation of age-associated BBB changes may offer insights into BBB homeostasis and may provide effective therapeutic strategies to protect it during aging.

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“…Several groups have examined pharmacotherapies for POCD in basic science models. Peng et al ( 246) utilized metformin as a potential treatment option for isofluraneinduced cognitive dysfunction in vivo (246). The research group utilized a sub-minimal alveolar concentration (MAC) of 1.3% isoflurane to induce cognitive dysfunction in murine models (246).…”

Section: Targeting the Neuro-immune Axismentioning

confidence: 99%

Anesthesia-mediated neuroinflammatory sequelae in post operative cognitive dysfunction: mechanisms and therapeutic implications

Smith,

Chen,

Shah

et al. 2024

Front. Anesthesiol.

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Post-operative cognitive dysfunction (POCD) is an iatrogenic cognitive decline with unclear etiology. While current hypotheses include surgical and pharmacological-induced neuroinflammatory mechanisms, the growing prevalence, especially amongst the geriatric population, emphasizes the ambiguity of the dysfunction. Recent studies have highlighted the potential role of general and regional anesthesia in the pathogenesis of POCD; these pharmacological effects have been demonstrated to disrupt blood-brain barrier integrity, influence microglial polarization, and have been linked to worsening prognoses in cognitive decline. Moreover, mechanical stress from surgical intervention and reperfusion injury may exacerbate the generation of reactive oxygen species (ROS), thereby increasing oxidative stress to the brain synergistically with blood-brain barrier disruptions. In previous studies, factors for the variable incidence and various risk factors have been explored. In this review, we examine the pharmacological effects of local, regional, and general anesthesia on molecular and cellular glial response, along with its intercellular interactions and previously reported clinical outcomes.

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Metformin alleviates prolonged isoflurane inhalation induced cognitive decline via reducing neuroinflammation in adult mice

Cited by 13 publications

References 58 publications

Aqueous Flare Changes in Ex-PRESS Glaucoma Shunt Eyes After 4.7 Tesla High-Field Magnetic Resonance Imaging

Aqueous Flare Changes in Ex-PRESS Glaucoma Shunt Eyes After 4.7 Tesla High-Field Magnetic Resonance Imaging

Alterations of the blood-brain barrier during aging

Anesthesia-mediated neuroinflammatory sequelae in post operative cognitive dysfunction: mechanisms and therapeutic implications

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