Dr. Jonas’ laboratory research focuses on improving neurological outcomes for patients undergoing cardiac surgical procedures on cardiopulmonary bypass. His current R01 grant focuses on white matter susceptibility to cardiac surgery. Other ongoing projects include investigating the use of near-infrared spectroscopy to guide surgery, examining the permeability of the blood brain barrier during cardiopulmonary bypass using a porcine model, exploring the cellular and molecular level responses to various bypass strategies and developing appropriate bypass management and adjunctive protection.
Using two transgenic mouse lines, analysis has identified OLs as a cellular target to reduce risks of white matter injury in immature white matter. Based on these results, the study has been the first to develop a combined experimental paradigm using rodent hypoxia and brain slice models to replicate the unique brain conditions in neonates with severe and complex congenital heart disease. Analysis has identified a uniquely susceptible cellular target of OGD-induced WM injury within the oligodendrocyte lineage. Studies have also defined cellular effects of preoperative hypoxia on each oligodendrocyte developmental stage thus contributing to future development of an optimal strategy of CPB/DHCA management for white matter protection in neonates with severe/complex congenital heart disease.
In addition to these findings, Dr. Jonas’ lab has demonstrated that astrocytes play an important role in white matter injury associated with cardiopulmonary bypass using hypothermia For designing cell-based regenerative strategies in perinatal brain injury including congenital heart disease induced hypoxia, the team has established innovative in vivo cell fate analysis in a porcine model The technique allows definition of endogenous neurogenesis/gliogenesis from neural stem/progenitor cells in the postnatal brain under normal conditions and after injury by trucking the cells labeled using cell-tracker green The unique impact of restricted oxygen supply in CHD patients has been investigated using a porcine hypoxia model. The porcine hypoxia model results in macroscopic changes in the developing brain very similar to those observed in CHD newborns. Preliminary data demonstrate that: i) labeled cells migrating from the neurogenic niche express specific markers of immature neurons in the cortex; ii) significant cellular and morphological changes occur in the neurogenic niche after hypoxia; and iii) there is a significant decrease in cell number of cortical immature neurons after hypoxia. The team hypothesizes that these cells play an important role in cortico-cortical connectivity.
Dr. Jonas’ laboratory has developed a new project titled “Antenatal Tetrahydrobiopterin Treatment for Complex CHD”, to improve neurological injury due to hypoxia in fetus with severe/complex CHD. In this project, they will test the hypothesis using rodent animal model: i) Decreased tetrahydrobiopterin (BH4) level is a critical mechanism underlying brain injury in the CHD fetus; and ii) Antenatal BH4 treatment.