ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2019
Induction of Neuronal PI3Kγ Contributes to Endoplasmic Reticulum Stress and Long-Term Functional Impairment in a Murine Model of Traumatic Brain Injury.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Temporal and Spatial Patterns of Glial Activation After Unilateral Cortical Injury in Rats.Life (Basel, Switzerland) · 2026Article
- Intravenous miR-30c therapy confers dual neurovascular protection and improves long-term recovery after ischemic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- An exploratory exome-wide machine learning analysis identifies candidate host gene signatures associated with Long COVID in a large admixed Brazilian cohort.Frontiers in medicine · 2026Article
- Neurotrauma induced retinal basement membrane COL4A1 defects are restored by adipose tissue derived mesenchymal stem cell concentrated conditioned medium.Stem cell research & therapy · 2025Article
- Attenuation of Ventilation-Induced Endoplasmic Reticulum Stress Associated with Lung Injury Through Phosphoinositide 3-Kinase-Gamma in a Murine Endotoxemia Model.International journal of molecular sciences · 2025Article
- Impact of prior exposures on biomarkers of blast during military tactical training.Frontiers in neurology · 2025Article
- Biomaterials in tissue repair and regeneration: key insights from extracellular matrix biology.Frontiers in medical technology · 2025Review
- J147 treatment protects against traumatic brain injury by inhibiting neuronal endoplasmic reticulum stress potentially via the AMPK/SREBP-1 pathway.Translational research : the journal of laboratory and clinical medicine · 2024Article
- The Importance of Phosphoinositide 3-Kinase in Neuroinflammation.International journal of molecular sciences · 2024Review
- Sestrin2 can alleviate endoplasmic reticulum stress to improve traumatic brain injury by activating AMPK/mTORC1 signaling pathway.Metabolic brain disease · 2024Review
- Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury.Cell death & disease · 2024Review
- Enhancement of the liver's neuroprotective role ameliorates traumatic brain injury pathology.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- m6A Methyltransferase METTL3 Reduces Hippocampal Neuron Apoptosis in a Mouse Model of Autism Through the MALAT1/SFRP2/Wnt/β-catenin Axis.Psychiatry investigation · 2022Article
- Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside.Pharmaceutics · 2022Review
- Inhibition of PI3Kγ by AS605240 plus low-dose tissue plasminogen activator (tPA) combination improves thrombolytic therapy in a rat model of embolic stroke.Neuroscience letters · 2020Article
- Inhibition of CD147 improves oligodendrogenesis and promotes white matter integrity and functional recovery in mice after ischemic stroke.Brain, behavior, and immunity · 2019Article
- The neuroprotective effects of Dexmedetomidine: key mechanisms focusing on neuronal programmed cell death.Frontiers in neurologyReview
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8 authors.
Funding
Abstract
Phosphoinositide 3-kinase γ (PI3Kγ) expressed in immune cells is linked to neuroinflammation in several neurological diseases. However, the expression and role of PI3Kγ in preclinical traumatic brain injury (TBI) have not been investigated. In WT mice, we found that TBI induced rapid and extensive expression of PI3Kγ in neurons within the perilesional cortex and the ipsilateral hippocampal subfields (CA1, CA3), which peaked between 1 and 3 days and declined significantly 7 days after TBI. Intriguingly, the induction of neuronal PI3Kγ in these subregions of the brain spatiotemporally coincided with both the TBI-induced activation of the neuronal ER stress pathway (p-eIF2α, ATF4, and CHOP) and neuronal cell death (marked by TUNEL-positive neurons) 3 days after TBI. Further, we show that the absence of PI3Kγ in knockout mice profoundly reduced the TBI-induced activation of the ER stress pathway and neuronal cell death. White matter disruption is a better predictor of long-term clinical outcomes than focal lesion size. We show that PI3Kγ deficiency not only reduced brain tissue loss but also alleviated white matter injury (determined by axonal injury and demyelination) up to 28 days after TBI. Importantly, PI3Kγ-knockout mice exhibited greater functional recovery including forepaw use, sensorimotor balance and coordination, and spatial learning and memory up to 28 days after TBI. These results unveil a previously unappreciated role for neuronal PI3Kγ in the regulation of ER stress associated with neuronal cell death, white matter damage, and long-term functional impairment after TBI.
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