Biomedicine Xagena

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Traumatic brain injury in murine model: subacute intranasal administration of tPA promotes neuroplasticity and improves functional recovery

Traumatic brain injury ( TBI ) is a major cause of death and long-term disability worldwide. To date, there are no effective pharmacological treatments for traumatic brain injury.

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.

Researchers have reported that tPA, administered by intranasal delivery during the subacute phase after traumatic brain injury, provides therapeutic benefit.

Animals with traumatic brain injury were treated intranasally with saline or tPA initiated 7 days after traumatic brain injury.
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 traumatic brain injury;

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;

4) increased the level of mature brain-derived neurotrophic factor.

The data suggest that subacute intranasal tPA treatment improves functional recovery and promotes brain neurogenesis and spinal cord axonal sprouting after traumatic brain injury, which may be mediated, at least in part, by tPA/plasmin-dependent maturation of brain-derived neurotrophic factor. ( Xagena )

Meng Y et al, PLoS ONE 2014; 9(9): e106238. doi:10.1371/journal.pone.0106238