ArticleProceedings of the National Academy of Sciences of the United States of America2018
Tissue plasminogen activator promotes white matter integrity and functional recovery in a murine model of traumatic brain injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases.Frontiers in neuroscience · 2020Pooled it
- Endothelial cells temporally orchestrate lymphocyte dynamics and functional outcomes after ischemic stroke.Fluids and barriers of the CNS · 2026Article
- CXCR3-mediated natural killer cell infiltration exacerbates white matter injury after intracerebral haemorrhage.Brain : a journal of neurology · 2025Article
- The Relationship Between Inflammation and the Development of Cerebral Ischaemia and Hypoxia in Traumatic Brain Injury-A Narrative Review.International journal of molecular sciences · 2025Review
- Genetic deletion of G protein-coupled receptor 56 aggravates traumatic brain injury through the microglial CCL3/4/5 upregulation targeted to CCR5.Cell death & disease · 2025Article
- Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.JCI insight · 2024Article
- Microglial histone deacetylase 2 is dispensable for functional and histological outcomes in a mouse model of traumatic brain injury.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Organoids Modeling Stroke in a Petri Dish.Biomedicines · 2024Review
- ASK1-K716R reduces neuroinflammation and white matter injury via preserving blood-brain barrier integrity after traumatic brain injury.Journal of neuroinflammation · 2023Article
- The BDNF mimetic R-13 attenuates TBI pathogenesis using TrkB-related pathways and bioenergetics.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- HSPB2 facilitates neural regeneration through autophagy for sensorimotor recovery after traumatic brain injury.JCI insight · 2023Article
- Regulatory T Cells Secrete IL10 to Suppress Neuroinflammation in Early Stage after Subarachnoid Hemorrhage.Medicina (Kaunas, Lithuania) · 2023Article
- Review
- The Unconventional Growth Factors Cerebral Dopamine Neurotrophic Factor and Mesencephalic Astrocyte-Derived Neurotrophic Factor Promote Post-ischemic Neurological Recovery, Perilesional Brain Remodeling, and Lesion-Remote Axonal Plasticity.Translational stroke research · 2023Article
- Loading neural stem cells on hydrogel scaffold improves cell retention rate and promotes functional recovery in traumatic brain injury.Materials today. Bio · 2023Article
- Insulin-like Growth Factor-1 Prevents Hypoxia/Reoxygenation-Induced White Matter Injury in Sickle Cell Mice.Biomedicines · 2023Article
- The Relationship of Astrocytes and Microglia with Different Stages of Ischemic Stroke.Current neuropharmacology · 2023Review
- Age-Related Alterations in Peripheral Immune Landscape with Magnified Impact on Post-Stroke Brain.Research (Washington, D.C.) · 2023Article
- Sulforaphane promotes white matter plasticity and improves long-term neurological outcomes after ischemic stroke via the Nrf2 pathway.Free radical biology & medicine · 2022Article
- Genetic deletion of Krüppel-like factor 11 aggravates traumatic brain injury.Journal of neuroinflammation · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Recombinant tissue plasminogen activator (tPA) is a Food and Drug Administration-approved thrombolytic treatment for ischemic stroke. tPA is also naturally expressed in glial and neuronal cells of the brain, where it promotes axon outgrowth and synaptic plasticity. However, there are conflicting reports of harmful versus neuroprotective effects of tPA in acute brain injury models. Furthermore, its impact on white matter integrity in preclinical traumatic brain injury (TBI) has not been thoroughly explored, although white matter disruption is a better predictor of long-term clinical outcomes than focal lesion volumes. Here we show that the absence of endogenous tPA in knockout mice impedes long-term recovery of white matter and neurological function after TBI. tPA-knockout mice exhibited greater asymmetries in forepaw use, poorer sensorimotor balance and coordination, and inferior spatial learning and memory up to 35 d after TBI. White matter damage was also more prominent in tPA knockouts, as shown by diffusion tensor imaging, histological criteria, and electrophysiological assessments of axon conduction properties. Replenishment of tPA through intranasal application of the recombinant protein in tPA-knockout mice enhanced neurological function, the structural and functional integrity of white matter, and postinjury compensatory sprouting in corticofugal projections. tPA also promoted neurite outgrowth in vitro, partly through the epidermal growth factor receptor. Both endogenous and exogenous tPA protected against white matter injury after TBI without increasing intracerebral hemorrhage volumes. These results unveil a previously unappreciated role for tPA in the protection and/or repair of white matter and long-term functional recovery after TBI.
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