scholarly journals Human Cerebral Organoid Implantation Alleviated the Neurological Deficits of Traumatic Brain Injury in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Zhongyuan Bao ◽  
Kaiheng Fang ◽  
Zong Miao ◽  
Chong Li ◽  
Chaojuan Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Cortical Neurons ◽  
Embryonic Stem ◽  
High Rate ◽  
Neurological Deficits ◽  
Spatial Learning And Memory ◽  
Electromyographic Activity

Traumatic brain injury (TBI) causes a high rate of mortality and disability, and its treatment is still limited. Loss of neurons in damaged area is hardly rescued by relative molecular therapies. Based on its disease characteristics, we transplanted human embryonic stem cell- (hESC-) derived cerebral organoids in the brain lesions of controlled cortical impact- (CCI-) modeled severe combined immunodeficient (SCID) mice. Grafted organoids survived and differentiated in CCI-induced lesion pools in mouse cortical tissue. Implanted cerebral organoids differentiated into various types of neuronal cells, extended long projections, and showed spontaneous action, as indicated by electromyographic activity in the grafts. Induced vascularization and reduced glial scar were also found after organoid implantation, suggesting grafting could improve local situation and promote neural repair. More importantly, the CCI mice’s spatial learning and memory improved after organoid grafting. These findings suggest that cerebral organoid implanted in lesion sites differentiates into cortical neurons, forms long projections, and reverses deficits in spatial learning and memory, a potential therapeutic avenue for TBI.

scholarly journals Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sujing Zhuang ◽  
Baogui Liu ◽  
Shifeng Guo ◽  
Yanzhong Xue ◽  
Lin Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Neuronal Apoptosis ◽  
Spatial Learning And Memory ◽  
Dependent Manner ◽  
Dose Dependent ◽  
And Oxidative Stress

Abstract Background Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Methods Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. Results GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. Conclusions GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

scholarly journals Zinc supplementation prevents depression and deficits in spatial learning and memory associated with traumatic brain injury in the rat

2011 ◽  
Vol 25 (S1) ◽  
Author(s):  
Elise C. Cope ◽  
Jacob W. VanLandingham ◽  
Angus G. Scrimgeour ◽  
Michelle L. Condlin ◽  
Shannon D. Gower‐Winter ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Learning And Memory ◽  
Spatial Learning ◽  
Zinc Supplementation ◽  
Spatial Learning And Memory

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

2020 ◽  
Author(s):  
Han Wang ◽  
Xiaoming Zhou ◽  
Lingyun Wu ◽  
Guangjie Liu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Neurons ◽  
Neurological Deficits ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Related Factor ◽  
Mice Model ◽  
Anti Inflammatory

Abstract 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.

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

2020 ◽  
Author(s):  
Han Wang ◽  
Xiaoming Zhou ◽  
Lingyun Wu ◽  
Guangjie Liu ◽  
Weidong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cortical Neurons ◽  
Neurological Deficits ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Related Factor ◽  
Mice Model ◽  
Anti Inflammatory

Abstract 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.

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