BDNF promotes neuronal survival after neonatal hypoxic-ischemic encephalopathy by up-regulating Stx1b and suppressing VDAC1

Xue, Lu‐Lu; Du, Ruo‐Lan; Hu, Yue; Xiong, Liu‐Lin; Su, Zhang-Yu; Ma, Zheng; Tan, Ya‐Xin; Jia, Lingyun; Hu, Qiao; Liu, Xuezheng; Wang, Ting-Hua

doi:10.1016/j.brainresbull.2021.05.013

Cited by 13 publications

(12 citation statements)

References 39 publications

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“…CREB can mediate the transcriptional activation of BDNF, 13 and as a target gene of CREB 42 . BDNF plays a crucial role in the anti‐neurotoxic effect and the promotion of neuronal survival and regeneration after ischemic brain injury 43,44 . The upregulation of BDNF significantly inhibits neuronal apoptosis 45 .…”

Section: Discussionmentioning

confidence: 99%

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Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p‐CREB/BDNF pathway in hypoxic‐ischemic neonatal rats

Liu

Zhou

et al. 2022

The FASEB Journal

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Neuronal apoptosis is one of the main pathological processes of hypoxic‐ischemic brain damage (HIBD) and is involved in the development of hypoxic‐ischemic encephalopathy (HIE) in neonates. Atorvastatin has been found to have neuroprotective effects in some nervous system diseases, but its role in regulating the pathogenesis of neonatal HIBD remains elusive. Thus, this study aimed to explore the effects and related mechanisms of atorvastatin on the regulation of neuronal apoptosis after HIBD in newborn rats. The rat HIBD model and the neuronal oxygen glucose deprivation (OGD) model were established routinely. Atorvastatin, cAMP inhibitor (SQ22536), and BDNF inhibitor (ANA‐12) were used to treat HIBD rats and OGD neurons. Cerebral infarction, learning and memory ability, cAMP/PKA/p‐CREB/BDNF signaling molecules, and apoptosis‐related indicators (TUNEL, cleaved caspase‐3, and Bax/Bcl2) were then examined. In vivo, atorvastatin reduced cerebral infarction, improved learning and memory ability, decreased the number of TUNEL‐positive neurons, inhibited the expression of cleaved caspase‐3 and Bax/Bcl2, and activated the cAMP/PKA/p‐CREB/BDNF pathway in the cerebral cortex after HIBD. In vitro, atorvastatin also decreased the apoptosis‐related indicators and activated the cAMP/PKA/p‐CREB/BDNF pathway in neurons after OGD. Furthermore, inhibition of cAMP or BDNF attenuated the effect of atorvastatin on the reduction of neuronal apoptosis, suggesting that atorvastatin inhibits HIBD‐induced neuronal apoptosis and alleviates brain injury in neonatal rats mainly by activating the cAMP/PKA/p‐CREB/BDNF pathway. In conclusion, atorvastatin may be developed as a potential drug for the treatment of neonatal HIE.

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Section: Discussionmentioning

confidence: 99%

“…42 BDNF plays a crucial role in the anti-neurotoxic effect and the promotion of neuronal survival and regeneration after ischemic brain injury. 43,44 The upregulation of BDNF significantly inhibits neuronal apoptosis. 45 HI can decrease BDNF expression in the cerebral cortex of rats.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p‐CREB/BDNF pathway in hypoxic‐ischemic neonatal rats

Liu

Zhou

et al. 2022

The FASEB Journal

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“…BDNF belongs to the neurotrophin family of growth factors (Xue et al, 2021) and is expressed at high levels in the developing brain; this protein has been proven to promote neurogenesis. Recently, a number of studies have reported that BDNF plays a crucial role in neurogenesis (Jaworska et al, 2019;Okamoto et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine alleviates olfactory cognitive dysfunction by promoting neurogenesis in the subventricular zone of hypoxic-ischemic neonatal rats

Chen

Deng

et al. 2022

Front. Pharmacol.

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Background: Hypoxic-ischemic brain damage (HIBD) is the main cause of neurological dysfunction in neonates. Olfactory cognitive function is important for feeding, the ability to detect hazardous situations and social relationships. However, only a few studies have investigated olfactory cognitive dysfunction in neonates with HIBD; furthermore, the specific mechanisms involved are yet to be elucidated. It has been reported that neurogenesis in the subventricular zone (SVZ) is linked to olfactory cognitive function. Recently, dexmedetomidine (DEX) has been shown to provide neuroprotection in neonates following HIBD. In the present study, we investigated whether DEX could improve olfactory cognitive dysfunction in neonatal rats following HIBD and attempted to determine the underlying mechanisms.Methods: We induced HIBD in rats using the Rice–Vannucci model, and DEX (25 μg/kg, i.p.) was administered immediately after the induction of HIBD. Next, we used triphenyl tetrazolium chloride (TTC) staining and the Zea-longa score to assess the success of modelling. The levels of BDNF, TNF-α, IL-1β and IL-6 were determined by western blotting. Immunofluorescence staining was used to detect microglial activation and microglial M1/M2 polarization as well as to evaluate the extent of neurogenesis in the SVZ. To evaluate the olfactory cognitive function, the rats in each group were raised until post-natal days 28–35; then, we performed the buried food test and the olfactory memory test.Results: Analysis showed that HIBD induced significant brain infarction, neurological deficits, and olfactory cognitive dysfunction. Furthermore, we found that DEX treatment significantly improved olfactory cognitive dysfunction in rat pups with HIBD. DEX treatment also increased the number of newly formed neuroblasts (BrdU/DCX) and neurons (BrdU/NeuN) in the SVZ by increasing the expression of BDNF in rat pups with HIBD. Furthermore, analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of inflammation and the promotion of M1 to M2 conversion in the microglia.Conclusion: Based on the present findings, DEX treatment could improve olfactory cognitive dysfunction in neonatal rats with HIBD by promoting neurogenesis in the SVZ and enhancing the expression of BDNF in the microglia. It was possible associated that DEX inhibited neuroinflammation and promoted M1 to M2 conversion in the microglia.

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“…Zea-Longa score was used to evaluate the successful establishment of animal models and the temporal alteration of neuronal impairment, the method is as follows: 0 point, no neurological deficits, double forelimb symmetrically stretching to the ground; 1 point, contralateral forelimb weakness and torso turning to the ipsilateral side when held by the tail; 2 points, circling to affected side; 3 points, failure to bear weight on affected side; and 4 points, no spontaneous locomotor activity or barrel rolling (Longa et al, 1989 ; Wang L. et al, 2021 ; Xue et al, 2021 ). The evaluations were performed by three professionals who were blinded to the experimental design.…”

Section: Methodsmentioning

confidence: 99%

Temporal alteration of microglia to microinfarcts in rat brain induced by the vascular occlusion with fluorescent microspheres

Shen

Cui

Zhang

et al. 2022

Front. Cell. Neurosci.

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Microglia, the resident immune cells in the central nervous system, can monitor the microenvironment and actively respond to ischemic stroke and other brain injuries. In this procedure, microglia and neurons can cross-talk via transmembrane chemokine, Fractalkine (CX3CL1), to impact one another. We used a rat model of multifocal microinfarcts induced by the injection of fluorescent microspheres into the right common carotid artery and examined the morphological alteration of blood vessels, microglia, astrocytes, and neurons at 6 h, 1, 7, and 14 days after modeling, along with neurobehavioral tests and the staining of CX3CL1 in this study. Our results demonstrated that in the infarcted regions, astrocytes and microglia activated in response to neuronal degeneration and upregulation of cleaved caspase-3, which occurred concurrently with vascular alteration and higher expression of CX3CL1. We provided sequential histological data to shed light on the morphological changes after modeling, which would help in the identification of new targets and the choice of the ideal time window for therapeutic intervention in ischemic stroke.

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BDNF promotes neuronal survival after neonatal hypoxic-ischemic encephalopathy by up-regulating Stx1b and suppressing VDAC1

Cited by 13 publications

References 39 publications

Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p‐CREB/BDNF pathway in hypoxic‐ischemic neonatal rats

Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p‐CREB/BDNF pathway in hypoxic‐ischemic neonatal rats

Dexmedetomidine alleviates olfactory cognitive dysfunction by promoting neurogenesis in the subventricular zone of hypoxic-ischemic neonatal rats

Temporal alteration of microglia to microinfarcts in rat brain induced by the vascular occlusion with fluorescent microspheres

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