Neuroprotective Role of Hypothermia in Hypoxic-ischemic Brain Injury: Combined Therapies using Estrogen

Toro-Urrego, Nicolás; Vesga-Jiménez, Diego Julián; Herrera, María Inés; Luaces, Juan Pablo; Capani, Francisco

doi:10.2174/1570159x17666181206101314

Cited by 12 publications

(6 citation statements)

References 181 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Models using hypoxia-simulating agents are among the in vitro approaches. These are based on producing, at the molecular level, the effects caused by low oxygen concentrations, primarily those based on the expression of hypoxia-inducible factor 1α (HIF1A) (Toro-Urrego et al, 2019). However, they do not consider removing glucose, the most important energy substrate in cerebral energy metabolism.…”

Section: Discussionmentioning

confidence: 99%

Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury

Toro-Urrego,

Luaces,

Bordet

et al. 2024

Preprint

View full text Add to dashboard Cite

. Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurological disability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads to insufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrial dysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemic brain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, a selective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whether raloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model. Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nM and 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygen-glucose deprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifene improved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.

show abstract

Section: Discussionmentioning

confidence: 99%

Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury

Toro-Urrego,

Luaces,

Bordet

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Hypoxic-ischemic brain injury (HIBI) is mainly characterized by a reduction in levels of blood flow and oxygen concentration, which results in an inefficient supply of nutrient substances to the brain [ 1 ]. HIBI is caused by birth asphyxia in neonates and cardiac arrest in infants or children, which is related to altered degrees of neurologic sequelae based upon the severity and length of HI [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Post-Treatment Sevoflurane Protects Against Hypoxic-Ischemic Brain Injury in Neonatal Rats by Downregulating Histone Methyltransferase G9a and Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)

Wang

Zhu

et al. 2021

Med Sci Monit

View full text Add to dashboard Cite

Background Perinatal hypoxia and subsequent reduction of cerebral blood flow leads to neonatal hypoxic-ischemic brain injury (HIBI), resulting in severe disability and even death. Preconditioning or post-conditioning with sevoflurane protects against cerebral injury. This study investigated the mechanism of sevoflurane in HIBI. Material/Methods The HIBI model of neonatal rats was established and the model rats were post-treated with sevoflurane. The oxygen-glucose deprivation (OGD) cell model was established, and the OGD cells were transfected with NRF2-siRNA plasmid and post-treated with sevoflurane. The Morris water maze test was used to detect the motor activity, spatial learning, and memory ability of HIBI rats. Histological stainings were performed to observe the area of cerebral infarction, record the number of neurons in the hippocampus, and assess neuron apoptosis. The levels of inflammatory factors were detected by ELISA. The protein levels of histone methyltransferase G9a and histone H3 lysine 9 (H3K9me2) were detected by western blot assay. The apoptosis was detected by flow cytometry. Results Sevoflurane post-treatment significantly shortened the escape latency of HIBI neonatal rats, increased the density of neurons, reduced the area of cerebral infarction, and decreased the levels of inflammatory factors and neuronal apoptosis. Sevoflurane post-treatment decreased G9a and H3K9me2 levels, and G9a level was negatively correlated with NRF2 level. NRF2 silencing reversed the alleviation of sevoflurane post-treatment on OGD-induced cell injury. Conclusions Sevoflurane post-treatment promotes NRF2 expression by inhibiting G9a and H3K9me2, thus alleviating HIBI in neonatal rats.

show abstract

“…2 HI brain injury involves a complex array of factors, with the main feature being a decrease in oxygen concentration and blood flow levels, eventually leading to an insufficient supply of nutrition to the brain. 3 Inflammation also represents a crucial factor leading to brain damage, with microglia playing an important role in the early inflammatory responses after HI injury. 4 As therapeutic interventions for these HI-induced effects are extremely limited, an increased understanding of the underlying mechanisms of this condition is sorely needed for the development of more effective measures in the prevention and treatment of neonatal HI encephalopathy.…”

Section: Introductionmentioning

confidence: 99%

<p>Hydrogen-Rich Saline Regulates Microglial Phagocytosis and Restores Behavioral Deficits Following Hypoxia-Ischemia Injury in Neonatal Mice via the Akt Pathway</p>

Ke¹,

Liu²,

Li³

et al. 2020

DDDT

View full text Add to dashboard Cite

Introduction: We have reported previously that hydrogen-rich saline (HS) plays a neuroprotective role in hypoxia-ischemia (HI) brain damage in newborn mice. However, the mechanisms for this neuroprotection resulting from HS remain unknown. In this study, we examined the potential for HS to exert effects upon microglial phagocytosis via involvement of the Akt signaling pathway as one of the neuroprotective mechanisms in response to neonatal HI. Methods: The HI brain injury model was performed on postnatal day (PND) 7 (modified Vannucci model). The acute brain damage was detected at 3 days after HI exposure. The behavioral and functional screening of the pups at PND11 and PND13 and their long-term outcomes (PND35, 28-days post-HI) were evaluated sensorimotor performance and cognitive functions, respectively. Results: The result showed that HS administration alleviated HI-induced edema, infract volume and cellular apoptosis within the cortex of neonatal mice. Accompanying these indices of neuroprotection from HS were reductions in HI-induced phagocytosis in microglia as demonstrated in vivo and in vitro, effects that were associated with increasing levels of Akt phosphorylation and improvements in neurobehavioral responses. These beneficial effects of HS were abolished in mice treated with an Akt inhibitor. Discussion: These results demonstrate that HS treatment attenuates neurobehavioral deficits and apoptosis resulting from HI, effects which were associated with reductions in phagocytosis and appear to involve the Akt signaling pathway.

show abstract

Neuroprotective Role of Hypothermia in Hypoxic-ischemic Brain Injury: Combined Therapies using Estrogen

Cited by 12 publications

References 181 publications

Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury

Raloxifene Protects Oxygen-glucose-deprived Astrocyte Cells Used To Mimic Hypoxic-ischemic Brain Injury

Post-Treatment Sevoflurane Protects Against Hypoxic-Ischemic Brain Injury in Neonatal Rats by Downregulating Histone Methyltransferase G9a and Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)

<p>Hydrogen-Rich Saline Regulates Microglial Phagocytosis and Restores Behavioral Deficits Following Hypoxia-Ischemia Injury in Neonatal Mice via the Akt Pathway</p>

Contact Info

Product

Resources

About