scholarly journals Hes1 negatively regulates neurogenesis in the adult mouse dentate gyrus following traumatic brain injury

2018 ◽  
Author(s):  
Rong Yan ◽  
Lin Zhang ◽  
Mengqi Li ◽  
Xiaozhi Liu ◽  
Xinyu Yang ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Adult Mouse

scholarly journals Enhancement of Neurogenesis and Memory by a Neurotrophic Peptide in Mild to Moderate Traumatic Brain Injury

Neurosurgery ◽  
2014 ◽  
Vol 76 (2) ◽  
pp. 201-215 ◽  
Author(s):  
Muhammad Omar Chohan ◽  
Olga Bragina ◽  
Syed Faraz Kazim ◽  
Gloria Statom ◽  
Narjes Baazaoui ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Parietal Cortex ◽  
Saline Solution ◽  
Neuronal Loss ◽  
Synaptic Density ◽  
Moderate Traumatic Brain Injury ◽  
Long Term Treatment ◽  
Newborn Neurons

ABSTRACT BACKGROUND: Traumatic brain injury (TBI) is a risk factor for Alzheimer disease (AD), a neurocognitive disorder with similar cellular abnormalities. We recently discovered a small molecule (Peptide 6) corresponding to an active region of human ciliary neurotrophic factor, with neurogenic and neurotrophic properties in mouse models of AD and Down syndrome. OBJECTIVE: To describe hippocampal abnormalities in a mouse model of mild to moderate TBI and their reversal by Peptide 6. METHODS: TBI was induced in adult C57Bl6 mice using controlled cortical impact with 1.5 mm of cortical penetration. The animals were treated with 50 nmol/d of Peptide 6 or saline solution for 30 days. Dentate gyrus neurogenesis, dendritic and synaptic density, and AD biomarkers were quantitatively analyzed, and behavioral tests were performed. RESULTS: Ipsilateral neuronal loss in CA1 and the parietal cortex and increase in Alzheimer-type hyperphosphorylated tau and A-β were seen in TBI mice. Compared with saline solution, Peptide 6 treatment increased the number of newborn neurons, but not uncommitted progenitor cells, in dentate gyrus by 80%. Peptide 6 treatment also reversed TBI-induced dendritic and synaptic density loss while increasing activity in tri-synaptic hippocampal circuitry, ultimately leading to improvement in memory recall on behavioral testing. CONCLUSION: Long-term treatment with Peptide 6 enhances the pool of newborn neurons in the dentate gyrus, prevents neuronal loss in CA1 and parietal cortex, preserves the dendritic and synaptic architecture in the hippocampus, and improves performance on a hippocampus-dependent memory task in TBI mice. These findings necessitate further inquiry into the therapeutic potential of small molecules based on neurotrophic factors.

scholarly journals Changes in TrkB–ERK1/2–CREB/Elk-1 Pathways in Hippocampal Mossy Fiber Organization after Traumatic Brain Injury

2004 ◽  
Vol 24 (8) ◽  
pp. 934-943 ◽  
Author(s):  
Bingren Hu ◽  
Chunli Liu ◽  
Helen Bramlett ◽  
Thomas J. Sick ◽  
Ofelia F. Alonso ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Signaling Pathways ◽  
Granule Cells ◽  
Mossy Fiber ◽  
Control Level ◽  
Mossy Fibers ◽  
Underlying Mechanism ◽  
Fiber Organization

Traumatic brain injury (TBI) leads to mossy fiber reorganization, which is considered to be a causative factor in the development of temporal lobe epilepsy. However, the underlying mechanism is not fully understood. Emerging evidence suggests that TrkB–ERK1/2–CREB/Elk-1 pathways are highly related to synaptic plasticity. This study used the rat fluid-percussion injury model to investigate activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways after TBI. Rats were subjected to 2.0-atm parasagittal TBI followed by 30 minutes, 4 hours, 24 hours, and 72 hours of recovery. After TBI, striking activation of TrkB–ERK1/2–CREB/Elk-1 signaling pathways in mossy fiber organization were observed with confocal microscopy and Western blot analysis. ERK1/2 was highly phosphorylated predominantly in hippocampal mossy fibers, whereas TrkB was phosphorylated both in the mossy fibers and the dentate gyrus region at 30 minutes and 4 hours of recovery after TBI. CREB was also activated at 30 minutes, peaked at 24 hours of recovery, and returned to the control level at 72 hours of recovery in dentate gyrus granule cells. Elk-1 phosphorylation was seen in CA3 neurons at 4 hours after TBI. The results suggest that the signaling pathways of TrkB–ERK1/2–CREB/Elk-1 are highly activated in mossy fiber organization, which may contribute to mossy fiber reorganization seen after TBI.

scholarly journals Selective death of newborn neurons in hippocampal dentate gyrus following moderate experimental traumatic brain injury

2008 ◽  
Vol 86 (10) ◽  
pp. 2258-2270 ◽  
Author(s):  
Xiang Gao ◽  
Ying Deng‐Bryant ◽  
Wongil Cho ◽  
Kimberly M. Carrico ◽  
Edward D. Hall ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Hippocampal Dentate Gyrus ◽  
Selective Death ◽  
Newborn Neurons ◽  
Experimental Traumatic Brain Injury

scholarly journals Traumatic Brain Injury Severity Affects Neurogenesis in Adult Mouse Hippocampus

2016 ◽  
Vol 33 (8) ◽  
pp. 721-733 ◽  
Author(s):  
Xiaoting Wang ◽  
Xiang Gao ◽  
Stephanie Michalski ◽  
Shu Zhao ◽  
Jinhui Chen
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Adult Mouse ◽  
Injury Severity ◽  
Mouse Hippocampus ◽  
Traumatic Brain Injury Severity

scholarly journals Dentate Gyrus Proliferative Responses After Traumatic Brain Injury and Binge Alcohol in Adult Rats

2020 ◽  
Vol 15 ◽  
pp. 263310552096890
Author(s):  
Son T Ton ◽  
Natalie S Adamczyk ◽  
Jack P Gerling ◽  
Ian C Vaagenes ◽  
Joanna Y Wu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Proliferative Response ◽  
Male Rats ◽  
Public Health Issue ◽  
Adult Rats ◽  
Double Labeling ◽  
Post Traumatic

Background: Traumatic brain injury is a significant public health issue that results in serious disability in survivors. Traumatic brain injury patients are often intoxicated with alcohol when admitted to the hospital; however, it is not clear how acute intoxication affects recovery from a traumatic brain injury. Our group has previously shown that binge alcohol prior to traumatic brain injury resulted in long-term impairment in a fine sensorimotor task that was correlated with a decreased proliferative and neuroblast response from the subventricular zone. However, whether binge alcohol prior to traumatic brain injury affects the proliferative response in the hippocampal dentate gyrus is not yet known. Methods: Male rats underwent binge alcohol (3 g/kg/day) by gastric gavage for 3 days prior to traumatic brain injury. Cell proliferation was labeled by BrdU injections following traumatic brain injury. Stereological quantification and immunofluorescence confocal analysis of BrdU+ cells in the hippocampal dorsal dentate gyrus was performed at 24 hours, 1 week and 6 weeks post traumatic brain injury. Results: We found that either traumatic brain injury alone or binge alcohol alone significantly increased dentate gyrus proliferation at 24 hours and 1 week. However, a combined binge alcohol and traumatic brain injury regimen resulted in decreased dentate gyrus proliferation at 24 hours post-traumatic brain injury. At the 6 week time point, binge alcohol overall reduced the number of BrdU+ cells. Furthermore, more BrdU+ cells were found in the dentate hilar region of alcohol traumatic brain injury compared to vehicle traumatic brain injury groups. The location and double-labeling of these mismigrated BrdU+ cells was consistent with hilar ectopic granule cells. Conclusion: The results from this study showed that pre-traumatic brain injury binge alcohol impacts the injury-induced proliferative response in the dentate gyrus in the short-term and may affect the distribution of newly generated cells in the dentate gyrus in the long-term.

scholarly journals Ketogenic Diet as a potential treatment for traumatic brain injury in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Meirav Har-Even ◽  
Vardit Rubovitch ◽  
Whitney A. Ratliff ◽  
Bar Richmond-Hacham ◽  
Bruce A. Citron ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Dentate Gyrus ◽  
Ketogenic Diet ◽  
Cognitive Abilities ◽  
Ketone Bodies ◽  
Temporal Cortex ◽  
Closed Head Injury ◽  
Standard Diet ◽  
Post Injury

AbstractTraumatic brain injury (TBI) is a brain dysfunction without present treatment. Previous studies have shown that animals fed ketogenic diet (KD) perform better in learning tasks than those fed standard diet (SD) following brain injury. The goal of this study was to examine whether KD is a neuroprotective in TBI mouse model. We utilized a closed head injury model to induce TBI in mice, followed by up to 30 days of KD/SD. Elevated levels of ketone bodies were confirmed in the blood following KD. Cognitive and behavioral performance was assessed post injury and molecular and cellular changes were assessed within the temporal cortex and hippocampus. Y-maze and Novel Object Recognition tasks indicated that mTBI mice maintained on KD displayed better cognitive abilities than mTBI mice maintained on SD. Mice maintained on SD post-injury demonstrated SIRT1 reduction when compared with uninjured and KD groups. In addition, KD management attenuated mTBI-induced astrocyte reactivity in the dentate gyrus and decreased degeneration of neurons in the dentate gyrus and in the cortex. These results support accumulating evidence that KD may be an effective approach to increase the brain’s resistance to damage and suggest a potential new therapeutic strategy for treating TBI.

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