ArticleNeurobiology of disease2012
Subacute intranasal administration of tissue plasminogen activator increases functional recovery and axonal remodeling after stroke in rats.
Article in Neurobiology of disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Governor vessel acupuncture therapy in experimental ischemic stroke: A systematic review and meta-analysis.Medicine · 2025Pooled it
- From the Lab to Patients: a Systematic Review and Meta-Analysis of Mesenchymal Stem Cell Therapy for Stroke.Translational stroke research · 2020Pooled it
- Intrathecal versus intravenous umbilical cord mesenchymal stem cells for ischemic stroke sequelae.Stem cells translational medicine · 2025Trial
- Article
- Dysfunctional connectivity within hippocampal and entorhinal networks underlies early-life iron deficiency induced social recognition deficits, a preliminary study.Scientific reports · 2026Article
- The promise of stem cell therapies for cellular recovery after stroke.Inflammopharmacology · 2025Review
- New Wine in an Old Bottle: tPA for Ischemic Stroke Management.Translational stroke research · 2025Article
- Modulation of the proteoglycan receptor PTPσ promotes white matter integrity and functional recovery after intracerebral hemorrhage stroke in mice.Journal of neuroinflammation · 2022Article
- The use of recombinant tissue plasminogen activator in in acute ischemic stroke is associated with increased level of BDNF.Journal of thrombosis and thrombolysis · 2021Article
- MiR-17-92 enriched exosomes derived from multipotent mesenchymal stromal cells enhance axon-myelin remodeling and motor electrophysiological recovery after stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Taking central nervous system regenerative therapies to the clinic: curing rodentsNeural regeneration research · 2020Review
- Deficiency of tPA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice.Aging and disease · 2019Article
- The Plasminogen Activation System Promotes Neurorepair in the Ischemic Brain.Current drug targets · 2019Review
- Tissue plasminogen activator promotes white matter integrity and functional recovery in a murine model of traumatic brain injury.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Subacute intranasal administration of tissue plasminogen activator improves stroke recovery by inducing axonal remodeling in mice.Experimental neurology · 2018Article
- Potential of Stem Cell-Based Therapy for Ischemic Stroke.Frontiers in neurology · 2018Review
- Sensitivity of diffusion MRI to perilesional reactive astrogliosis in focal ischemia.NMR in biomedicine · 2017Article
- Assessment of C-phycocyanin effect on astrocytes-mediated neuroprotection against oxidative brain injury using 2D and 3D astrocyte tissue model.Scientific reports · 2015Article
- Article
- Tissue-type plasminogen activator is a neuroprotectant in the central nervous system.Frontiers in cellular neuroscience · 2015Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
As a thrombolytic agent, application of recombinant tissue plasminogen activator (tPA) to ischemic stroke is limited by the narrow time window and side effects on brain edema and hemorrhage. This study examined whether tPA, administered by intranasal delivery directly targeting the brain and spinal cord, provides therapeutic benefit during the subacute phase after stroke. Adult male Wistar rats were subjected to permanent right middle cerebral artery occlusion (MCAo). Animals were treated intranasally with saline, 60 μg or 600 μg recombinant human tPA at 7 and 14days after MCAo (n=8/group), respectively. An adhesive-removal test and a foot-fault test were used to monitor functional recovery. Biotinylated dextran amine (BDA) was injected into the left motor cortex to anterogradely label the corticorubral tract (CRT) and the corticospinal tract (CST). Naive rats (n=6) were employed as normal control. Animals were euthanized 8 weeks after stroke. Compared with saline treated animals, significant functional improvements were evident in rats treated with 600 μg tPA (p<0.05), but not in 60 μg tPA treated rats. Furthermore, 600 μg tPA treatment significantly enhanced both CRT and CST sprouting originating from the contralesional cortex into the denervated side of the red nucleus and cervical gray matter compared with control group (p<0.01), respectively. The behavioral outcomes were highly correlated with CRT and CST axonal remodeling. Our data suggest that delayed tPA intranasal treatment provides therapeutic benefits for neurological recovery after stroke by, at least in part, promoting neuronal remodeling in the brain and spinal cord.
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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.