Efficacy of acute administration of inhaled argon on traumatic brain injury in mice

Moro, Federico; Fossi, Francesca; Magliocca, Aurora; Pascente, Rosaria; Sammali, Eliana; Baldini, Federico; Tolomeo, Daniele; Micotti, Edoardo; Citerio, Giuseppe; Stocchetti, Nino; Fumagalli, Francesca; Magnoni, Sandra; Latini, Roberto; Ristagno, Giuseppe; Zanier, Elisa R.

doi:10.1016/j.bja.2020.08.027

Cited by 32 publications

(53 citation statements)

References 40 publications

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“…After the cognitive function tests, all mice were sacrificed, and the brain tissues were dissected. To determine whether Alzheimer's-like pathology and synaptic impairments can be accelerated by mTBI at a relatively early chronic stage ( 23 , 24 ), HE staining, immunofluorescence (IF) staining, and immunohistochemistry (IHC) were performed to evaluate cell density in the brain, the degree of Aβ plaque deposition in the brain, and SYN expression in the brain. Furthermore, the activation and phenotype of microglia were determined by IF staining and Western blotting after the 1st, 2nd, 3rd, and 4th weeks of TBI.…”

Section: Methodsmentioning

confidence: 99%

Traumatic Brain Injury Accelerates the Onset of Cognitive Dysfunction and Aggravates Alzheimer's-Like Pathology in the Hippocampus by Altering the Phenotype of Microglia in the APP/PS1 Mouse Model

Kumal

et al. 2021

Front. Neurol.

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An increasing number of studies have suggested that traumatic brain injury (TBI) is associated with some neurodegenerative diseases, including Alzheimer's disease (AD). Various aspects of the mechanism of TBI-induced AD have been elucidated. However, there are also studies opposing the view that TBI is one of the causes of AD. In the present study, we demonstrated that TBI exacerbated the disruption of hippocampal-dependent learning and memory, worsened the reductions in neuronal cell density and synapse formation, and aggravated the deposition of Aβ plaques in the hippocampi of APP/PS1 mice. We also found that TBI rapidly activated microglia in the central nervous system (CNS) and that this effect lasted for at least for 3 weeks. Furthermore, TBI boosted Aβ-related microglia-mediated neuroinflammation in the hippocampi of APP/PS1 mice and the transformation of microglia toward the proinflammatory phenotype. Therefore, our experiments suggest that TBI accelerates the onset of cognitive dysfunction and Alzheimer-like pathology in the APP/PS1 mouse model, at least partly by altering microglial reactions and polarization.

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Section: Methodsmentioning

confidence: 99%

Traumatic Brain Injury Accelerates the Onset of Cognitive Dysfunction and Aggravates Alzheimer's-Like Pathology in the Hippocampus by Altering the Phenotype of Microglia in the APP/PS1 Mouse Model

Kumal

et al. 2021

Front. Neurol.

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“…Before each test, mice were trained in three habituation trials. Performance was scored as the sum of the number of foot faults during the two tests (best score 0) [32].…”

Section: Beam Walking Testmentioning

confidence: 99%

“…Neurological parameters were assessed in eight tests including vision, proprioception, motor strength and posture, as previously described [32]. The result obtained in each of the eight tests was summed to obtain the overall SNAP score.…”

Section: Snap Testmentioning

confidence: 99%

In-depth characterization of a mouse model of post-traumatic epilepsy for biomarker and drug discovery

Sapia

Moro

Montanarella

et al. 2021

acta neuropathol commun

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Post-traumatic epilepsy (PTE) accounts for 5% of all epilepsies and 10–20% of the acquired forms. The latency between traumatic brain injury (TBI) and epilepsy onset in high-risk patients offers a therapeutic window for intervention to prevent or improve the disease course. However, progress towards effective treatments has been hampered by the lack of sensitive prognostic biomarkers of PTE, and of therapeutic targets. There is therefore a pressing clinical need for preclinical PTE models suitable for biomarker discovery and drug testing. We characterized in-depth a model of severe TBI induced by controlled cortical impact evolving into PTE in CD1 adult male mice. To identify sensitive measures predictive of PTE development and severity, TBI mice were longitudinally monitored by video-electrocorticography (ECoG), examined by MRI, and tested for sensorimotor and cognitive deficits and locomotor activity. At the end of the video-ECoG recording mice were killed for brain histological analysis. PTE occurred in 58% of mice with frequent motor seizures (one seizure every other day), as determined up to 5 months post-TBI. The weight loss of PTE mice in 1 week after TBI correlated with the number of spontaneous seizures at 5 months. Moreover, the recovery rate of the sensorimotor deficit detected by the SNAP test before the predicted time of epilepsy onset was significantly lower in PTE mice than in those without epilepsy. Neuroscore, beam walk and cognitive deficit were similar in all TBI mice. The increase in the contusion volume, the volume of forebrain regions contralateral to the lesioned hemisphere and white matter changes over time assessed by MRI were similar in PTE and no-PTE mice. However, brain histology showed a more pronounced neuronal cell loss in the cortex and hippocampus contralateral to the injured hemisphere in PTE than in no-PTE mice. The extensive functional and neuropathological characterization of this TBI model, provides a tool to identify sensitive measures of epilepsy development and severity clinically useful for increasing PTE prediction in high-risk TBI patients. The high PTE incidence and spontaneous seizures frequency in mice provide an ideal model for biomarker discovery and for testing new drugs.

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“…It has the lowest bloodgas partition coefficient among anesthetic gases (122). It has the advantage of being non-flammable and non-teratogenic, and it has less cardiovascular effects and no adverse effects on cognitive function in animal models (123)(124)(125)(126). In recent years, there has been increased interest in noble gases as novel treatments for ischemic and traumatic brain injury (127)(128)(129).…”

Section: Xenonmentioning

confidence: 99%

Inhaled Gases as Therapies for Post–Cardiac Arrest Syndrome: A Narrative Review of Recent Developments

et al. 2021

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Despite recent advances in the management of post–cardiac arrest syndrome (PCAS), the survival rate, without neurologic sequelae after resuscitation, remains very low. Whole-body ischemia, followed by reperfusion after cardiac arrest (CA), contributes to PCAS, for which established pharmaceutical interventions are still lacking. It has been shown that a number of different processes can ultimately lead to neuronal injury and cell death in the pathology of PCAS, including vasoconstriction, protein modification, impaired mitochondrial respiration, cell death signaling, inflammation, and excessive oxidative stress. Recently, the pathophysiological effects of inhaled gases including nitric oxide (NO), molecular hydrogen (H2), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H2, and Xe for treating PCAS. Recent basic and clinical research has shown that these gases have cytoprotective effects against PCAS. Nevertheless, there are likely differences in the mechanisms by which these gases modulate reperfusion injury after CA. Further preclinical and clinical studies examining the combinations of standard post-CA care and inhaled gas treatment to prevent ischemia–reperfusion injury are warranted to improve outcomes in patients who are being failed by our current therapies.

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Efficacy of acute administration of inhaled argon on traumatic brain injury in mice

Cited by 32 publications

References 40 publications

Traumatic Brain Injury Accelerates the Onset of Cognitive Dysfunction and Aggravates Alzheimer's-Like Pathology in the Hippocampus by Altering the Phenotype of Microglia in the APP/PS1 Mouse Model

Traumatic Brain Injury Accelerates the Onset of Cognitive Dysfunction and Aggravates Alzheimer's-Like Pathology in the Hippocampus by Altering the Phenotype of Microglia in the APP/PS1 Mouse Model

In-depth characterization of a mouse model of post-traumatic epilepsy for biomarker and drug discovery

Inhaled Gases as Therapies for Post–Cardiac Arrest Syndrome: A Narrative Review of Recent Developments

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