In general, our laboratory is interested in the molecular and cellular mechanisms of neuroprotection that occur in response to ischemic stress, acute brain injury and aging. Most strategies to reduce, slow and repair the severity of brain injuries have focused almost exclusively on neurons. We have focused our research on the potential of astrocytes as a novel theurapeutic avenue for brain treatment. Astrocytes are known to play a crucial role in supporting and protecting neuronal function and in modulating brain energy metabolism. A therapeutic strategy that increases energy production is inherently robust, since the number of potential neuroprotective processes that benefit are significantly higher than a single molecular target.
Talley Watts L, Sprague S, Zheng W, Garling RJ, Jimenez D, Digicaylioglu M, Lechleiter J. Purinergic 2Y1 receptor stimulation decreases cerebral edema and reactive gliosis in a traumatic brain injury model. J Neurotrauma. 2013 Jan 1;30(1):55-66.
Paredes RM, Bollo M, Holstein D, Lechleiter JD. Luminal Ca2+ depletion during the unfolded protein response in Xenopus oocytes: cause and consequence. Cell Calcium. 2013 Apr;53(4):286-96.
Diekman CO, Fall CP, Lechleiter JD, Terman D. Modeling the neuroprotective role of enhanced astrocyte mitochondrial metabolism during stroke. Biophys J. 2013 Apr 16;104(8):1752-63.
Zheng W, Talley Watts L, Holstein DM, Wewer J, Lechleiter JD. P2Y1R-initiated, IP3R-dependent stimulation of astrocyte mitochondrial metabolism reduces and partially reverses ischemic neuronal damage in mouse. J Cereb Blood Flow Metab. 2013 Apr;33(4):600-11.
Lin AL, Zheng W, Halloran JJ, Burbank RR, Hussong SA, Hart MJ, Javors M, Shih YY, Muir E, Solano Fonseca R, Strong R, Richardson AG, Lechleiter JD, Fox PT, Galvan V. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease. J Cereb Blood Flow Metab. 2013 Sep;33(9):1412-21.