Improving Brain Cell Function

Purinergic Treatment in Stroke model, Reverses Mitochondrial Depolarization in Astrocytes

impact of single-vessel blood clots on neuronal morphologyThe impact of single-vessel blood clots on neuronal morphology (green fluorescence) and on mitochondria (labeled with the potential sensitive dye TMRM; red fluorescence) was recorded before the initial thrombosis (3A), three hours after thrombosis (3B) where significant depolarization of astrocyte mitochondria (loss of red fluorescence) and significant disruption of neuronal cells and processes (green “beading”) is observed. At three hours, treatment was administered via tail-vein injection, and images at three hours later (six hours after thrombosis) (3C), show treatment has resulted in repolarization of the astrocyte mitochondria and partial reversal of the neuronal beading. (3D) A histogram of astrocyte mitochondrial potentials (pooled from 4 mice) and in Zheng et al2013 quantifies the repolarization after purinergic treatment (red bars).

Treatment in Stroke model, Partially Reverses Neuronal Damage

Neurons (green flourescence) observed in vivo before the initial mouse thrombosis (4A), three hours after the thrombosis (4B), four hours after the thrombosis and one hour after tail-vein treatment injection (4C), and six hours after the thrombosis (three post treatment) (4D). Note the reversal of neuronal blebbing in the inset, the first indication of ischemic injury. (4E) is a plot of the percentage of neurites that are blebbing.Neurons observed in vivo

For further detail, see: Zheng, W., Talley Watts, L., Holstein, D.M., Wewer, J. & Lechleiter, J.D. P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse. J Cereb Blood Flow Metab 33, 600-11 (2013).

Developing innovative neuroprotection therapies for Traumatic Brain Injuries (TBI), concussions, stroke, and neurodegenerative disorders