Aim: Traumatic brain injury (TBI) in infancy and childhood is a cause of death and a permanent disability. Young animals have more brain water than adult animals and typically the juvenile brain swells more than the adult brain after injury. However, therapeutic treatments for juvenile TBI (jTBI) are often based on adult physiology. Aquaporin 4 (AQP4), a water channel, is a possible therapeutic candidate, but, its role in juvenile brain swelling following TBI has not been studied. These experiments were designed to correlate the level of AQP4 expression with the edema formation using MRI after TBI.
Methods: A P17 day juvenile rat TBI (jTBI) controlled cortical impact (CCI) model used in using a 1 mm blunt tip piston to induce the trauma directly onto the cortex. MRI was performed at 1, 3, 7 and 28 days after jTBI followed by AQP4 immunolabeling. AQP4 staining was quantified using an infrared-scanner (LiCor) and epifluorescence microscopy.
Results: A significant decrease in ADC and increased T2 values were observed at 1 day after CCI in all ROI which reflected edema formation. At 3 days ADC values were normalized while T2s were still significantly elevated consistent with the onset of edema resolution. In the contused area, the number of neurons was decreased and GFAP staining was increased at 3 days, corresponding to the gliosis. Significant increased AQP4 expression within the contusion was coincident with the normalization MRI changes at 3 and 7 days. However, increase of AQP4 expression was also observed on astrocyte end-feet in contact with blood vessels distant from the site of the impact. At 28 days AQP4 expression normalized throughout the brain except in the contusion.
Conclusion: AQP4 expression was increased during the period of active edema resolution in the contusion and peri-contusional region, as we have previously observed in a stroke model. In adult TBI, decreased AQP4 expression was observed early after trauma. Our results suggest that traumatic pathological mechanisms are different between young and adult animals. This key finding should be considered in the future development of new drugs acting on AQPs to treat the edema formation after juvenile TBI.