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- W2153338009 endingPage "e106238" @default.
- W2153338009 startingPage "e106238" @default.
- W2153338009 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." @default.
- W2153338009 created "2016-06-24" @default.
- W2153338009 creator A5005508444 @default.
- W2153338009 creator A5009105694 @default.
- W2153338009 creator A5011056392 @default.
- W2153338009 creator A5042353405 @default.
- W2153338009 creator A5057596405 @default.
- W2153338009 creator A5085097885 @default.
- W2153338009 creator A5085252735 @default.
- W2153338009 date "2014-09-03" @default.
- W2153338009 modified "2023-09-27" @default.
- W2153338009 title "Subacute Intranasal Administration of Tissue Plasminogen Activator Promotes Neuroplasticity and Improves Functional Recovery following Traumatic Brain Injury in Rats" @default.
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