When administered as a nasal spray, t-PA may improve functional recovery in patients with less severe forms of traumatic brain injury (TBI), according to a study published September 3 in PLoS One.
Seven days after laboratory rats withstood TBI, investigators treated them intranasally with saline or t-PA. Compared with saline treatment, subacute intranasal t-PA treatment significantly improved the animals’ cognitive and sensorimotor functional recovery, reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, 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 increased the level of mature brain-derived neurotrophic factor.
“Using this novel procedure in our earlier stroke studies, we found significant improvement in neurologic function,” said Michael Chopp, PhD, Scientific Director of the Henry Ford Neuroscience Institute in Detroit. “We essentially repeated the experiment on laboratory rats with subacute TBI with similarly remarkable results. As in stroke treated intranasally with t-PA, our subjects showed greatly improved functional outcome and rewiring of the cortical spinal tract.”
Although the damage resulting from stroke can be reduced if t-PA is administered intravenously within 4.5 hours, IV t-PA also has potentially harmful side effects, including swelling of the brain and hemorrhage. Researchers at Henry Ford Hospital found that the effective treatment window could be extended to as long as two weeks for laboratory rats dosed with t-PA in a nasal spray, which avoids the harmful side effects of IV injection.
Previous research has indicated that drugs administered through the nose directly target the brain and spinal cord, although researchers do not yet fully understand how this targeting occurs. Although the new study offers hope that a drug treatment will emerge, no effective pharmacologic therapy is available yet.
These most recent findings suggest that t-PA has the potential to be a noninvasive treatment for subacute TBI, thus helping the brain restore function to damaged cells. The investigators noted that further animal studies will be required to determine the best dose and the appropriate time window for optimal intranasal treatment.