Dataset Information

Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

ABSTRACT:

Background

Hypoxic-ischemic brain damage (HIBD) significantly affects neurodevelopment in infants and is a leading cause of severe neurological morbidity and mortality in neonates. Our previous study found that photobiomodulation therapy (PBMT) improves the impaired spatial learning and memory of HIBD rat models. However, the neuroprotective mechanism conferred by PBMT in HIBD is unclear.

Methods

In the present study, HIBD model rats were treated with PBMT at 5 mW/cm² per day in the dark for 14 days (10 min each day), and primary neural stem cells (NSCs) after oxygen-glucose deprivation (OGD) were treated with PBMT for 10 min at 1, 5, 10, and 20 mW/cm² in the dark. PBMT promoted hippocampal neural stem cell (NSC) proliferation in vivo and in vitro.

Results

Mechanistically, PBMT upregulated phosphatidylinositol 3 kinase (PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated glycogen synthase kinase 3 beta (p-GSK-3β), β-catenin, and cyclin D1 expression in vivo and in vitro, promoting NSC proliferation. Furthermore, both LY294002 (a PI3K inhibitor) and IWR-1 (a Wnt/β-catenin inhibitor) inhibited the PBMT promotion of NSC proliferation after OGD and suppressed β-catenin and cyclin D1 expression in vitro.

Conclusions

PBMT improved the spatial learning and memory of HIBD rats and promoted hippocampal NSC proliferation through the AKT/GSK-3β/β-catenin pathway.

SUBMITTER: Liao Z

PROVIDER: S-EPMC8848383 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

Liao Zhaoying Z Zhou Xuanzi X Li Siyu S Jiang Wei W Li Tingsong T Wang Nanqing N Xiao Nong N

Annals of translational medicine 20220101 2

<h4>Background</h4>Hypoxic-ischemic brain damage (HIBD) significantly affects neurodevelopment in infants and is a leading cause of severe neurological morbidity and mortality in neonates. Our previous study found that photobiomodulation therapy (PBMT) improves the impaired spatial learning and memory of HIBD rat models. However, the neuroprotective mechanism conferred by PBMT in HIBD is unclear.<h4>Methods</h4>In the present study, HIBD model rats were treated with PBMT at 5 mW/cm<sup>2</sup> p ...[more]

PMID: 35282079

Similar Datasets

Project description:Neonatal hypoxic-ischemic (HI) injury is a severe complication often leading to neonatal death and long-term neurobehavioral deficits in children. Currently, the only treatment option available for neonatal HI injury is therapeutic hypothermia. However, the necessary specialized equipment, possible adverse side effects, and limited effectiveness of this therapy creates an urgent need for the development of new HI treatment methods. Photobiomodulation (PBM) has been shown to be neuroprotective against multiple brain disorders in animal models, as well as limited human studies. However, the effects of PBM treatment on neonatal HI injury remain unclear. Methods: Two-minutes PBM (808 nm continuous wave laser, 8 mW/cm2 on neonatal brain) was applied three times weekly on the abdomen of pregnant rats from gestation day 1 (GD1) to GD21. After neonatal right common carotid artery ligation, cortex- and hippocampus-related behavioral deficits due to HI insult were measured using a battery of behavioral tests. The effects of HI insult and PBM pretreatment on infarct size; synaptic, dendritic, and white matter damage; neuronal degeneration; apoptosis; mitochondrial function; mitochondrial fragmentation; oxidative stress; and gliosis were then assessed. Results: Prenatal PBM treatment significantly improved the survival rate of neonatal rats and decreased infarct size after HI insult. Behavioral tests revealed that prenatal PBM treatment significantly alleviated cortex-related motor deficits and hippocampus-related memory and learning dysfunction. In addition, mitochondrial function and integrity were protected in HI animals treated with PBM. Additional studies revealed that prenatal PBM treatment significantly alleviated HI-induced neuroinflammation, oxidative stress, and myeloid cell/astrocyte activation. Conclusion: Prenatal PBM treatment exerts neuroprotective effects on neonatal HI rats. Underlying mechanisms for this neuroprotection may include preservation of mitochondrial function, reduction of inflammation, and decreased oxidative stress. Our findings support the possible use of PBM treatment in high-risk pregnancies to alleviate or prevent HI-induced brain injury in the perinatal period.

Project description:Neonatal hypoxic-ischemic encephalopathy (HIE) is considered a major cause of death and long-term neurological injury in newborns. Studies have demonstrated that oxidative stress and apoptosis play a major role in the progression of neonatal HIE. Echinocystic acid (EA), a natural plant extract, shows great antioxidant and antiapoptotic activities in various diseases. However, it has not yet been reported whether EA exerts a neuroprotective effect against neonatal HIE. Therefore, this study was undertaken to explore the neuroprotective effects and potential mechanisms of EA in neonatal HIE using in vivo and in vitro experiments. In the in vivo study, a hypoxic-ischemic brain damage (HIBD) model was established in neonatal mice, and EA was administered immediately after HIBD. Cerebral infarction, brain atrophy and long-term neurobehavioral deficits were measured. Hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and dihydroethidium (DHE) staining were performed, and the contents of malondialdehyde (MDA) and glutathione (GSH) were detected. In the in vitro study, an oxygen-glucose deprivation/reperfusion (OGD/R) model was employed in primary cortical neurons, and EA was introduced during OGD/R. Cell death and cellular ROS levels were determined. To illustrate the mechanism, the PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 were used. The protein expression levels of p-PI3K, PI3K, p-Akt, Akt, Nrf2, NQO1, and HO-1 were measured by western blotting. The results showed that EA treatment significantly reduced cerebral infarction, attenuated neuronal injury, and improved brain atrophy and long-term neurobehavioral deficits in neonatal mice subjected to HIBD. Meanwhile, EA effectively increased the survival rate in neurons exposed to OGD/R and inhibited oxidative stress and apoptosis in both in vivo and in vitro studies. Moreover, EA activated the PI3K/Akt/Nrf2 pathway in neonatal mice following HIBD and in neurons after OGD/R. In conclusion, these results suggested that EA alleviated HIBD by ameliorating oxidative stress and apoptosis via activation of the PI3K/Akt/Nrf2 signaling pathway.

Dataset Information

Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

Background

Methods

Results

Conclusions

Publications

Activation of the AKT/GSK-3β/β-catenin pathway via photobiomodulation therapy promotes neural stem cell proliferation in neonatal rat models of hypoxic-ischemic brain damage.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets