ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2012
Combination therapy targeting Akt and mammalian target of rapamycin improves functional outcome after controlled cortical impact in mice.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
46 citing papers in PubMed, 74 citations in OpenAlex.
- Cottonseed Oil Attenuates Traumatic Brain Injury by Inhibiting AKT/GSK-3β-mediated Neuroinflammatory Responses.Molecular neurobiology · 2026Article
- USP4 modulates ZBP1 ubiquitination to regulate microglial PANoptosis and functional outcomes following traumatic brain injury.Cell death and differentiation · 2026Article
- Article
- Activation of AMPK/OPA1 pathway alleviates traumatic brain damage by regulating mitophagy.Acta cirurgica brasileira · 2025Article
- Motor skill learning modulates striatal extracellular vesicles' content in a mouse model of Huntington's disease.Cell communication and signaling : CCS · 2024Article
- Treatment with Rapamycin in Animal Models of Traumatic Brain Injuries; a Systematic Review and Meta-Analysis.Archives of academic emergency medicine · 2024Review
- Genetic inhibition of RIPK3 ameliorates functional outcome in controlled cortical impact independent of necroptosis.Cell death & disease · 2021Article
- IGF1-Stimulated Posttraumatic Hippocampal Remodeling Is Not Dependent on mTOR.Frontiers in cell and developmental biology · 2021Article
- Synaptic RTP801 contributes to motor-learning dysfunction in Huntington's disease.Cell death & disease · 2020Article
- Neurodegenerative pathways as targets for acquired epilepsy therapy development.Epilepsia open · 2020Review
- Modeling Controlled Cortical Impact Injury in 3D Brain-Like Tissue Cultures.Advanced healthcare materials · 2020Article
- Lipopolysaccharide induces neuroinflammation in microglia by activating the MTOR pathway and downregulating Vps34 to inhibit autophagosome formation.Journal of neuroinflammation · 2020Article
- MicroRNA-23a-3p improves traumatic brain injury through modulating the neurological apoptosis and inflammation response in mice.Cell cycle (Georgetown, Tex.) · 2020Article
- Converging early responses to brain injury pave the road to epileptogenesis.Journal of neuroscience research · 2019Review
- Interleukin-1 Receptor 1 Deletion in Focal and Diffuse Experimental Traumatic Brain Injury in Mice.Journal of neurotrauma · 2019Article
- Exogenous Hydrogen Sulfide Offers Neuroprotection on Intracerebral Hemorrhage Injury Through Modulating Endogenous HFrontiers in cellular neuroscience · 2019Article
- The mTOR kinase inhibitor rapamycin enhances the expression and release of pro-inflammatory cytokine interleukin 6 modulating the activation of human microglial cells.EXCLI journal · 2019Article
- Effects of rapamycin and curcumin on inflammation and oxidative stress in vitro and in vivo - in search of potential anti-epileptogenic strategies for temporal lobe epilepsy.Journal of neuroinflammation · 2018Article
- Lysosomal damage after spinal cord injury causes accumulation of RIPK1 and RIPK3 proteins and potentiation of necroptosis.Cell death & disease · 2018Article
- Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Akt and mammalian target of rapamycin (mTOR) are both activated after traumatic brain injury (TBI), however complex interplay between the two hampers deciphering their functional implications in vivo. We examined the effects of single and combination inhibitors of Akt/mTOR in a mouse controlled cortical impact (CCI) model. Following CCI, phospho-Akt-473 (p-Akt) and -S6 ribosomal protein (p-S6RP), a downstream substrate of mTOR, were increased in cortical and hippocampal brain homogenates (P<0.05 versus sham). At 24 hours, p-S6RP was detected in neurons and was robustly induced in microglia and astrocytes in injured hippocampus. In vivo activity of Akt and mTOR inhibitors administered separately was confirmed by reduced expression of p-GSK3β (P<0.01) or p-S6RP (P<0.05), respectively, after CCI. Importantly, administration of Akt and mTOR inhibitors together (but not of either alone) improved postinjury motor (P=0.02) and cognitive deficits (hidden platform trials, P=0.001; probe trials, P<0.05), decreased propidium iodide-positive cells in CA1 and CA3 (P<0.005), and unexpectedly increased p-GSK3β in hippocampus. Although the roles of Akt and mTOR in the pathogenesis of TBI remain to be fully elucidated, dual inhibition of Akt and mTOR may have therapeutic potential for TBI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.