ArticlePloS one2014
Subacute intranasal administration of tissue plasminogen activator promotes neuroplasticity and improves functional recovery following traumatic brain injury in rats.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- The Nasal-Brain Drug Delivery Route: Mechanisms and Applications to Central Nervous System Diseases.MedComm · 2025Review
- Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury.Scientific reports · 2023Article
- Altered Hippocampal and Striatal Expression of Endothelial Markers and VIP/PACAP Neuropeptides in a Mouse Model of Systemic Lupus Erythematosus.International journal of molecular sciences · 2023Article
- Wireless charging-mediated angiogenesis and nerve repair by adaptable microporous hydrogels from conductive building blocks.Nature communications · 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
- Plasminogen deficiency causes reduced angiogenesis and behavioral recovery after stroke in mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- The Role of BDNF in Experimental and Clinical Traumatic Brain Injury.International journal of molecular sciences · 2021Review
- Inhibiting endogenous tissue plasminogen activator enhanced neuronal apoptosis and axonal injury after traumatic brain injury.Neural regeneration research · 2020Article
- 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
- The Potential of Stem Cells in Treatment of Traumatic Brain Injury.Current neurology and neuroscience reports · 2018Review
- DRα1-MOG-35-55 treatment reduces lesion volumes and improves neurological deficits after traumatic brain injury.Metabolic brain disease · 2017Article
- Inosine enhances recovery of grasp following cortical injury to the primary motor cortex of the rhesus monkey.Restorative neurology and neuroscience · 2016Article
- Strategies targeting endogenous neurogenic cell response to improve recovery following traumatic brain injury.Brain research · 2016Review
- Dysfunction in the coagulation system and schizophrenia.Translational psychiatry · 2016Review
- Anti-Nogo-A Immunotherapy Does Not Alter Hippocampal Neurogenesis after Stroke in Adult Rats.Frontiers in neuroscience · 2016Article
- Improvement of Psychotic Symptoms and the Role of Tissue Plasminogen Activator.International journal of molecular sciences · 2015Review
- Investigational agents for treatment of traumatic brain injury.Expert opinion on investigational drugs · 2015Review
- VGF (TLQP-62)-induced neurogenesis targets early phase neural progenitor cells in the adult hippocampus and requires glutamate and BDNF signaling.Stem cell research · 2014Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) is a major cause of death and long-term disability worldwide. To date, there are no effective pharmacological treatments for TBI. Recombinant human tissue plasminogen activator (tPA) is the effective drug for the treatment of acute ischemic stroke. In addition to its thrombolytic effect, tPA is also involved in neuroplasticity in the central nervous system. However, tPA has potential adverse side effects when administered intravenously including brain edema and hemorrhage. Here we report that tPA, administered by intranasal delivery during the subacute phase after TBI, provides therapeutic benefit. Animals with TBI were treated intranasally with saline or tPA initiated 7 days after TBI. Compared with saline treatment, subacute intranasal tPA treatment significantly 1) improved cognitive (Morris water maze test) and sensorimotor (footfault and modified neurological severity score) functional recovery in rats after TBI, 2) reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, 3) enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and 4) increased the level of mature brain-derived neurotrophic factor. Our data suggest that subacute intranasal tPA treatment improves functional recovery and promotes brain neurogenesis and spinal cord axonal sprouting after TBI, which may be mediated, at least in part, by tPA/plasmin-dependent maturation of brain-derived neurotrophic factor.
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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.