- Authors: Campbell, M., Hanrahan, F., Gobbo, O. L., Kelly, M. E., Kiang, A. S., Humphries, M. M., Nguyen, A. T., Ozaki, E., Keaney, J., Blau, C. W., Kerskens, C. M., Cahalan, S. D., Callanan, J. J., Wallace, E., Grant, G. A., Doherty, C. P., Humphries, P.
- Year: 2012
- Journal: Nat Commun 3 849
- Applications: in vivo / siRNA / in vivo-jetPEI
siRNA (20 μg) was diluted in 100 μl of a 10% glucose solution. The volume was adjusted to 200 μl using RNAse/DNAse free water. Solutions were mixed and briefly centrifuged. In a separate tube, 6.4 μl in vivo-jetPEI was diluted in 100 μl of a 10% glucose solution. The volume was adjusted to 200 μl, using RNAse/DNAse free water, and solutions were briefly mixed. The 200 μl in vivo-jetPEI solution was then added to the siRNA solution, vortexed and briefly centrifuged. Solutions were then incubated for 15 min, at room temperature, to allow complexes to form. Mice were injected slowly in the tail vein (400 μl final volume per mouse).
Traumatic brain injury is the leading cause of death in children and young adults globally. Malignant cerebral oedema has a major role in the pathophysiology that evolves after severe traumatic brain injury. Added to this is the significant morbidity and mortality from cerebral oedema associated with acute stroke, hypoxic ischemic coma, neurological cancers and brain infection. Therapeutic strategies to prevent cerebral oedema are limited and, if brain swelling persists, the risks of permanent brain damage or mortality are greatly exacerbated. Here we show that a temporary and size-selective modulation of the blood-brain barrier allows enhanced movement of water from the brain to the blood and significantly impacts on brain swelling. We also show cognitive improvement in mice with focal cerebral oedema following administration in these animals of short interfering RNA directed against claudin-5. These observations may have profound consequences for early intervention in cases of traumatic brain injury, or indeed any neurological condition where cerebral oedema is the hallmark pathology.