Dynamic cerebral blood flow changes with FOXOs stimulation are involved in neuronal damage associated with high-altitude cerebral edema in mice

Shi, Huaxiang; Li, Pengfei; Zhou, Hu; Nie, Zhiyong; Zhang, Jingxin; Sui, Xin; Guo, Jiahao; Wang, Yongan; Wang, Liyun

doi:10.1016/j.brainres.2022.147987

Cited by 3 publications

(2 citation statements)

References 30 publications

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“…Almost everyone who climbs to high-altitude above 4500 m experiences headache, weariness, dizziness, or vertigo [ 53 ]. In addition, previous research has also demonstrated that AHAI significantly affects both locomotor activity and rotarod behavior tests in mice [ 54 ], and the findings in this study are consistent with above experiment. It is suggested that this model may effectively restore the high altitude environment and make the tested zebrafish show the pathological state similar to AHAI.…”

Section: Discussionsupporting

confidence: 92%

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

Ma,

et al. 2024

Heliyon

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Section: Discussionsupporting

confidence: 92%

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

Ma,

et al. 2024

Heliyon

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“…Exposure to hypoxia increases the release of excitatory and inhibitory synaptic transmitters in neurons, causing excitability, neuronal damage, and even brain cell death ( Revah et al, 2016 ). HH exposure activates neuronal apoptotic signaling and triggers neuronal apoptosis ( Shi et al, 2022 ). Neuronal damage directly affects the synthesis, uptake, and release of central neurotransmitters, which in turn affects interneural excitatory neurotransmitter transmission and synaptic plasticity, thus causing cognitive impairment ( Sharma et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

CX3CL1/CX3CR1 signal mediates M1-type microglia and accelerates high-altitude-induced forgetting

Wang

Xie

Niu

et al. 2023

Front. Cell. Neurosci.

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IntroductionHypoxia-induced neuronal damage is the primary cause of cognitive impairment induced by high-altitude exposure. Microglia play a crucial regulatory role in the central nervous system (CNS) homeostasis and synaptic plasticity. M1-type polarized microglia are suspected to be responsible for CNS injury under hypoxic conditions, but the exact molecular mechanism is still unelucidated.MethodsCX3CR1 knock out and wide type mice were exposed to a simulated plateau at 7000 m for 48 h to construct the model of hypobaric hypoxia-induced memory impairment. The memory impairment of mice was assessed by Morris water maze. The dendritic spine density in the hippocampus was examined by Golgi staining. The synapses in the CA1 region and the number of neurons in the DG region were examined by immunofluorescence staining. The synapses in microglia activation and phagocytosis were examined by immunofluorescence. The levels of CX3CL1/CX3CR1 and their downstream proteins were detected. CX3CR1 knockout primary microglia were treated with CX3CL1 combined with 1% O2. The levels of proteins related to microglial polarization, the uptake of synaptosome and phagocytotic ability of microglia were detected.ResultsIn this study, mice exposed to a simulated 7000 m altitude for 48 h developed significant amnesia for recent memories, but no significant change in their anxiety levels was observed. Hypobaric hypoxia exposure (7000 m altitude above sea level for 48 h) resulted in synapse loss in the CA1 region of the hippocampus, but no significant changes occurred in the total number of neurons. Meanwhile, microglia activation, increased phagocytosis of synapses by microglia, and CX3CL1/CX3CR1 signal activation were observed under hypobaric hypoxic exposure. Further, we found that after hypobaric hypoxia exposure, CX3CR1-deficient mice showed less amnesia, less synaptic loss in the CA1 region, and less increase in M1 microglia, compared to their wildtype siblings. CX3CR1-deficient microglia did not exhibit M1-type polarization in response to either hypoxia or CX3CL1 induction. Both hypoxia and CX3CL1 induced the phagocytosis of synapses by microglia through the upregulation of microglial phagocytosis.DiscussionThe current study demonstrates that CX3CL1/CX3CR1 signal mediates the M1-type polarization of microglia under high-altitude exposure and upregulates microglial phagocytosis, which increases the phagocytosis of synapses in the CA1 region of the hippocampus, causing synaptic loss and inducing forgetting.

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Aeromedical evacuation-relevant hypobaria following traumatic brain injury in rats contributes to cerebral blood flow depression, altered neurochemistry, and increased neuroinflammation

Proctor,

Xu,

Guo

et al. 2024

J Cereb Blood Flow Metab

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Aircraft cabins are routinely pressurized to the equivalent of 8000 ft altitude. Exposure of lab animals to aeromedical evacuation relevant hypobaria after traumatic brain injury worsens neurological outcomes, which is paradoxically exacerbated by hyperoxia. This study tested the hypothesis that exposure of rats to hypobaria following cortical impact reduces cerebral blood flow, increases neuroinflammation, and alters brain neurochemistry. Rats were exposed to simulated ground (normobaric) or air (hypobaric 8000 ft) transport, under normoxia or hyperoxia, 24 hr after trauma. Hypobaria exposure resulted in lower cerebral blood flow to the contralateral cortex and bilateral thalamus during flight and increased delayed cortical inflammation (ED1 immunoreactivity) at 14 days post injury. Impacted rats exposed to hypobaria had higher cortical creatine levels compared rats maintained at sea level. Exposure to the combination of hyperoxia and hypobaria resulted in the greatest reduction in cortical blood flow and total creatine during flight which persisted up to two weeks. In conclusion, hypoperfusion during hypobaria exposure could contribute to worsening of neuroinflammation and neurochemical imbalances. The presence of excessive O2 during hypobaria results in long-term suppression of cerebral blood flow, indicating that supplemental O2 should be titrated during hypobaria to maintain normoxia.

show abstract

Dynamic cerebral blood flow changes with FOXOs stimulation are involved in neuronal damage associated with high-altitude cerebral edema in mice

Cited by 3 publications

References 30 publications

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

Rapid altitude displacement induce zebrafish appearing acute high altitude illness symptoms

CX3CL1/CX3CR1 signal mediates M1-type microglia and accelerates high-altitude-induced forgetting

Aeromedical evacuation-relevant hypobaria following traumatic brain injury in rats contributes to cerebral blood flow depression, altered neurochemistry, and increased neuroinflammation

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