Inhibition of Elevated Hippocampal CD24 Reduces Neurogenesis in Mice With Traumatic Brain Injury

Han, Wei; Zhou, Xiaoming; Xu, Weidong; Tao, Tao; Liu, Guangjie; Gao, Yongyue; Lu, Yaxin; Wu, Lingyun; Yang, Zhu; Yuan, Bin; Hang, Chun-Hua; Li, Wei

doi:10.1016/j.jss.2019.07.082

“…Quantitative real-time PCR Q-PCR was performed as previously described [36]. Total mRNA was isolated from tissues (Additional le 1: Figure S1) using the Trizol reagent (TAKARA, Japan) and measured using spectrophotometric analysis (OD260/OD280).…”

Section: Rna Interferencementioning

confidence: 99%

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Wang

¹

,

Zhou²,

Wu

³

et al. 2020

Preprint

Self Cite

2

1

0

View full text Add to dashboard Cite

Background: Aucubin (Au), an iridoid glycoside from natural plants, has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H 2 O 2 -induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model. Methods: In vitro experiments, the various concentrations of Au (50 μg/ml, 100 μg/ml or 200 μg/ml) were added in culture medium at 0h and 6h after neurons stimulated by H 2 O 2 (100μM). After exposed for 12 hours, neurons were collected for western blot (WB), immunofluorescence and M29,79-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. In vivo experiments, Au (20 mg/kg or 40 mg/kg) was administrated intraperitoneally at 30 min, 12 h, 24 h, and 48 h after modeling. Brain water content, neurological deficits and cognitive functions were measured at specific time, respectively. Cortical tissue around focal trauma was collected for WB, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA) at 72 h after TBI. RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with Au (40 mg/kg) treatment. Mice were intracerebroventricularly administrated with lentivirus at 72 h before TBI establishment. The cortex was obtained at 72 h after TBI and used for WB and q-PCR. Results: Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis both in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au. Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

show abstract

“…Q-PCR was performed as previously described [36]. Total mRNA was isolated from tissues using the Trizol reagent (TAKARA, Japan) and measured using spectrophotometric analysis (OD260/OD280).…”

Section: Quantitative Real-time Pcrmentioning

confidence: 99%

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Wang

¹

,

Zhou²,

Wu

³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Aucubin (Au) has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H 2 O 2 -induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.Methods: Neuronal apoptosis, brain water content, histological damages and neurological deficits and cognitive functions were measured. We performed western blot, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA). RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with intraperitoneal injection of Au.Results: We found that Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system. pathobiological features of secondary brain damage [4,5]. Excessive production of free radicals leads to lipid peroxidation, protein degradation, and genotoxicity leading to cellular and tissue damage [6].The brain is an organ with a high content of polyunsaturated fatty acids, which also makes it vulnerable to free radical attack and lipid peroxidation [7]. In addition, OS damage to mitochondrial function can collapse the cellular bioenergetics leading to cell apoptosis [6]. These OS-induced damaged cells releases damage associated molecular patterns (DAMPs; e.g. ATP, RNA, high mobility group box-1) to initiate or exacerbate neuroinflammation, which can also further promote ROS generation [8,9]. Extensive animal data suggest that elevated antioxidant response and reduced inflammation would attenuate brain damage [10][11][12].Nuclear factor erythroid-2 related factor 2 (Nrf2) has considerable neuroprotective effects in central nervous system (CNS) diseases[13-15]. Nrf2 is a transcription factor that takes part in regulation of cellular response to oxidative stress. Under normal physiological conditions, Kelch-like ECH-associated protein 1 (Keap1) combines with Nrf2 and enhances Nrf2 degradation. Once stimulated, Nrf2 translocates into the nucleus and binds to the antioxidant response element (ARE) in the promoter of antioxidant genes, thereby inducing the expression of antioxidant and detoxifi...

show abstract

“…On the 24 th day after the trauma, the mice were administered the MWM test with minor modifications to assess their cognitive functions based on previous experiments [36]. Visual cues of figures were hung on the wall of the tank.…”

Section: Mwm Testmentioning

confidence: 99%

“…The transfection of LV expressing Nrf2-specific shRNA or negative control shRNA for mice brains in vivo were conducted according to previously described methods [36]. After induction of anesthesia, mice with scalp incisions were placed in a stereotaxic device, then a cranial burr hole (2.…”

Section: Rna Interferencementioning

confidence: 99%

See 1 more Smart Citation

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Wang

¹

,

Zhou²,

Wu

³

et al. 2020

Preprint

Self Cite

1

0

View full text Add to dashboard Cite

Background: Aucubin (Au) has anti-oxidative and anti-inflammatory bioactivities; however, its effects on a traumatic brain injury (TBI) model remain unknown. We explored the potential role of Au in a H2O2-induced oxidant damage in primary cortical neurons and weight-drop induced-TBI in a mouse model.Methods: Neuronal apoptosis, brain water content, histological damages and neurological deficits and cognitive functions were measured. We performed western blot, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, Nissl staining, quantitative real time polymerase chain reaction (q-PCR), immunofluorescence/immunohistochemistry and enzyme linked immunosorbent assay (ELISA). RNA interference experiments were performed to determine the effects of Nuclear factor erythroid-2 related factor 2 (Nrf2) on TBI mice with intraperitoneal injection of Au.Results: We found that Au enhanced the translocation of Nrf2 into the nucleus, activated antioxidant enzymes, suppressed excessive generation of reactive oxygen species (ROS) and reduced cell apoptosis in vitro and vivo experiments. In the mice model of TBI, Au markedly attenuated brain edema, histological damages and improved neurological and cognitive deficits. Au significantly suppressed high mobility group box 1(HMGB1)-mediated aseptic inflammation. Nrf2 knockdown in TBI mice blunted the antioxidant and anti-inflammatory neuroprotective effects of the Au.Conclusions: Taken together, our data suggest that Au provides a neuroprotective effect in TBI mice model by inhibiting oxidative stress and inflammatory responses; the mechanisms involve triggering Nrf2-induced antioxidant system.

show abstract

Inhibition of Elevated Hippocampal CD24 Reduces Neurogenesis in Mice With Traumatic Brain Injury

Cited by 15 publications

References 36 publications

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Aucubin alleviates oxidative stress and inflammation via Nrf2-mediated signaling activity in experimental traumatic brain injury

Contact Info

Product

Resources

About