Foxo3a Transcriptionally Upregulates AQP4 and Induces Cerebral Edema Following Traumatic Brain Injury

Kapoor, Suraj; Kim, Seon Myung; Farook, Justin M.; Mir, Sajad Ahmad; Saha, Rahul; Sen, Nilkantha

doi:10.1523/jneurosci.2756-13.2013

Cited by 53 publications

(57 citation statements)

References 33 publications

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“…The nuclear accumulation of Foxo3a is augmented by a decrease in phosphorylation at its Ser256 residue because of the inactivation of Akt after TBI. The depletion of Foxo3a in mice rescues cytotoxic edema by preventing the induction of AQP4 and attenuates memory impairment after TBI in mice (Kapoor et al, 2013). The increased calcium influx leads to the activation of several cellular pathways, including the calcium-dependent enzymes nitric oxide synthases (NOS) and phospholipases, which cause the production of free nitrogen radicals and reactive oxygen species (ROS); this leads to further excitotoxic damage (Xiong et al, 2001).…”

Section: Secondary Mechanisms Associated With Tbimentioning

confidence: 99%

Traumatic brain injury: a risk factor for neurodegenerative diseases

Gupta

Sen

2016

Reviews in the Neurosciences

118

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AbstractTraumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

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Section: Secondary Mechanisms Associated With Tbimentioning

confidence: 99%

Traumatic brain injury: a risk factor for neurodegenerative diseases

Gupta

Sen

2016

Reviews in the Neurosciences

118

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“…The procedure was done based on our previously published protocol (Farook et al, 2013; Kapoor et al, 2013; Sen et al, 2017). Briefly, 8– 12-week old adult male C57BL/6 (Jackson Laboratory) mice were anesthetized with xylazine (8 mg/kg)/ketamine (60 mg/kg) and subjected to a sham injury or controlled cortical impact.…”

Section: Methodsmentioning

confidence: 99%

“…A 1 mm micro punch was collected from the pericontusional cortex or the corresponding pericontusional hemisphere as described previously (Farook et al, 2013; Kapoor et al, 2013; Mir et al, 2014; Sen et al, 2017). Tissue was placed in RIPA buffer (containing protease and phosphatase inhibitor), sonicated, and centrifuged for 5 min at 12,000 × g at 4°C.…”

Section: Methodsmentioning

confidence: 99%

“…Blots were incubated overnight at 4°C in primary antibody Cyclin Dl, (Cell Signalling, 1:500 dilution), total NRF1 (Santa Cruz Biotech., 1:500 dilution), p300 (Sigma-Aldrich, 1:500 dilution), total PGClα (Santa Cruz Biotech., 1:500 dilution), Nuclear NRF1 (Abeam, abl75932), nuclear PGClα (Abeam ab54481), TFAM (Santa Cruz Biotech., 1:500 dilution), CoxII (Santa Cruz Biotech., 1:500 dilution), and Actin (Sigma-Aldrich, 1:5000 dilution) followed by a 2 h incubation with a Licor IRDye secondary antibody at room temperature. Blots were visualized using a Fi-Cor Odyssey near-infrared imaging system, and densitometry analysis was performed using Quantity One software (Bio-Rad) (Farook et al, 2013; Kapoor et al, 2013; Mir et al, 2014). The intensity of each band was determined by ImageJ software, and the changes in the experimental band were represented as the fold change as described previously (Sen et al, 2017; Sen and Sen, 2016).…”

Section: Methodsmentioning

confidence: 99%

“…Protein-protein interactions and protein acetylation were measured by co-immunoprecipitation assay per our method (Farook et al, 2013; Kapoor et al, 2013; Mir et al, 2014; Sen et al, 2017). Briefly, treated or untreated cells were homogenized in lysis buffer containing 50 mm Tris, pH 7.4, 150mM NaCl, 0.5% (v/v) tween-20, 50mM Tris (pH 7.5), 1mM EDTA with protease and phosphatase inhibitor by passing through 26- gauge syringe needle and centrifuged at 12,000 × g for 5 min.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury

Saha

Gupta

Sen

et al. 2018

Neurobiology of Disease

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Cell cycle activation has been associated with varying types of neurological disorders including brain injury. Cyclin D1 is a critical modulator of cell cycle activation and upregulation of Cyclin D1 in neurons contributes to the pathology associated with traumatic brain injury (TBI). Mitochondrial mass is a critical factor to maintain the mitochondrial function, and it can be regulated by different signaling cascades and transcription factors including NRF1. However, the underlying mechanism of how TBI leads to impairment of mitochondrial mass following TBI remains obscure. Our results indicate that augmentation of CyclinD1 attenuates mitochondrial mass formation following TBI. To elucidate the molecular mechanism, we found that Cyclin D1 interacts with a transcription factor NRF1 in the nucleus and prevents NRF1’s interaction with p300 in the pericontusional cortex following TBI. As a result, the acetylation level of NRF1 was decreased, and its transcriptional activity was attenuated. This event leads to a loss of mitochondrial mass in the pericontusional cortex following TBI. Intranasal delivery of Cyclin D1 RNAi immediately after TBI rescues transcriptional activation of NRF1 and recovers mitochondrial mass after TBI.

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Neuroprotective effects of FK866 against traumatic brain injury: Involvement of p38/ERK pathway

Tan

Chen

Ren

et al. 2020

Ann Clin Transl Neurol

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Objective: FK866 is an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), which exhibits neuroprotective effects in ischemic brain injury. However, in traumatic brain injury (TBI), the role and mechanism of FK866 remain unclear. The present research was aimed to investigate whether FK866 could attenuate TBI and clarified the underlying mechanisms. Methods: A controlled cortical impact model was established, and FK866 at a dose of 5 mg/kg was administered intraperitoneally at 1 h and 6 h, then twice per day post-TBI until sacrifice. Brain water content, Evans blue dye extravasation, modified neurological severity scores (mNSS), Morris water maze test, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and western blot were performed. Results: The results demonstrated that FK866 significantly mitigated the brain edema, blood-brain barrier (BBB) disruption, and ameliorated the neurological function post-TBI. Moreover, FK866 decreased the number of Iba-1-positive cells, GFAP-positive astrocytes, and AQP4-positive cells. FK866 reduced the protein levels of proinflammatory cytokines and inhibited NF-jB from translocation to the nucleus. FK866 upregulated the expression of Bcl-2, diminished the expression of Bax and caspase 3, and the number of apoptotic cells. Moreover, p38 MAPK and ERK activation were significantly inhibited by FK866. Interpretation: FK866 attenuated TBI-induced neuroinflammation and apoptosis, at least in part, through p38/ERK MAPKs signaling pathway. 742

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Foxo3a Transcriptionally Upregulates AQP4 and Induces Cerebral Edema Following Traumatic Brain Injury

Cited by 53 publications

References 33 publications

Traumatic brain injury: a risk factor for neurodegenerative diseases

Traumatic brain injury: a risk factor for neurodegenerative diseases

Activation of cyclin D1 affects mitochondrial mass following traumatic brain injury

Neuroprotective effects of FK866 against traumatic brain injury: Involvement of p38/ERK pathway

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