Middle aged CAMKII-Cre:&lt;i&gt;Cbs&lt;sup&gt;fl/fl&lt;/sup&gt;&lt;/i&gt; mice: a new model for studying perioperative neurocognitive disorders

Li, Zhen; He, Mengfan; Dai, Danqing; Gao, Xiaofei; Liang, Huazheng; Xiong, Lize

doi:10.1538/expanim.23-0065

Cited by 1 publication

(1 citation statement)

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“…These findings are consistent with our findings and clinical observations. Intriguingly, Xiong's team established a novel model for studying PND by inducing hyperhomocysteinemia in middleaged mice through intraperitoneal injection or gene editing, based on the evidences that increased serum homocysteine levels are a common characteristic associated with aggravated neuronal damage in aging and AD (Li et al, 2024;Zhang et al, 2024). Their research enlightened us that middle-aged mice with brain lymphatic drainage impairment may serve as another new model for reducing the need for old mice and saving time and costs in studying PND.…”

Section: Discussionmentioning

confidence: 99%

Surgery induces neurocognitive disorder via neuroinflammation and glymphatic dysfunction in middle-aged mice with brain lymphatic drainage impairment

Zhu,

Lin,

Yang

et al. 2024

Front. Neurosci.

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BackgroundBrain lymphatic drainage impairment is a prevalent characteristic in both aging and neurodegeneration. Surgery is more likely to induce excessive neuroinflammation and postoperative neurocognitive disorder (PND) among patients with aging and neurodegeneration. We hypothesized that surgical trauma may aggravate PND through preexisting cerebral lymphatic drainage impairment. However, there remains limited understanding about the role of surgery in changes of neurocognitive function in the populations with preoperative brain lymphatic drainage impairment. This study aims to expand our insight into surgery-induced glymphatic dysfunction, neuroinflammation and PND in middle-aged mice with preoperative brain lymphatic drainage impairment.Materials and methodsDeep cervical lymph nodes ligation (LdcLNs) was performed on middle-aged mice to establish preoperative brain lymphatic drainage impairment. A month later, laparotomy was performed on these mice with or without LdcLNs followed by analysis of brain neuroinflammation, glymphatic function, neuronal damage, and behavioral test.ResultsLdcLNs disrupted meningeal lymphatic drainage. In middle-aged mice with LdcLNs, surgery exacerbated more serious glymphatic dysfunction accompanied by aggravation of A1 astrocytes activation and AQP4 depolarization. Furthermore, surgery caused neuronal damage via reducing expression of neuronal nuclei (NeuN), post-synaptic density protein 95 (PSD95) and synaptophysin (SYP), as well as impairment in exploratory behavior and spatial working memory in middle-aged mice with LdcLNs. Additionally, surgery induced neuroinflammation with elevated microglia activation and increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, as well as activated more expression of HMGB1/TLR-4/NF-κB pathway in middle-aged mice with LdcLNs.ConclusionSurgery exacerbates neuroinflammation and glymphatic dysfunction, ultimately resulting in neuronal damage and neurocognitive disorder in middle-aged mice with preoperative brain lymphatic drainage impairment. These results suggest that brain lymphatic drainage impairment may be a deteriorating factor in the progression of PND, and restoring its function may serve as a potential strategy against PND.

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Section: Discussionmentioning

confidence: 99%