- Professor, Department of Neurosurgery
- (608) 263-4055
Ph.D. University of Hyderabad
Molecular Mechanisms of Inflammation, Neuronal Death, and Neurogenesis after Stroke
Gene Expression Profiling following CNS Injury
Acute insults to CNS alter the expression of several genes with significant functional consequences. To develop a viable therapy, it is essential to identify and understand the role of the novel molecular pathways affected by an insult. Using microarray analysis and proteomics, our lab identified inflammatory gene expression driven by pro-inflammatory transcription factors as a common molecular mechanism underlying excitotoxic pathologies.
Control of Post-ischemic Inflammation
The molecular mechanisms that modulate the inflammatory progression in brain are not well understood. When induced, suppressor of cytokine signaling (SOCS) family of proteins controls cytokine production by negative feedback regulation of JAK-STAT pathways. As cytokines promote inflammation and neuronal damage, we are evaluating the mechanism of action of ischemia-induced SOCS-3 and STAT-3 by using antisense and adenoviral vectors.
Induction of Cerebral Inflammation
Transcription factors Egr-1 and C-EBPß are known to induce pro-inflammatory cascades in mammals. We are currently analyzing the functional significance, down-stream effectors and the interactive mechanism of action of Egr-1 and C-EBP-ß in controlling focal ischemia-induced neuroinflammation.
Role of Inflammation in Stem Cell Proliferation after Stroke
Neurogenesis in the post-ischemic brain has tremendous potential to replace lost neurons. Inflammation is known to be detrimental to neurogenesis. Despite massive inflammation, neural progenitor cell proliferation significantly increases in the post-ischemic adult rat brain. We are trying to understand the significance of inflammatory mechanisms in modulating post-ischemic neurogenesis.
- Dharap A, Bowen K, Place R, Li LC, Vemuganti R (2009) Transient focal ischemia induces extensive temporal changes in rat cerebral MicroRNAome. J Cereb Blood Flow Metab (Online early).
- Kapadia R, Yi JH, Vemuganti R. (2008) Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists. Front Biosci 13:1813-26, 2008.
- Tureyen K, Brooks N, Bowen K, Svaren J, Vemuganti R (2008) Transcription Factor Early Growth Response-1 Induction Mediates Inflammatory Gene Expression and Brain Damage following Transient Focal Ischemia. J Neurochem 105: 1313-1324.
- Vemuganti R. (2008) Therapeutic potential of PPAR-gamma activation in stroke.PPAR Res In press.
- Tureyen K, Kapadia R, Bowen KK, Satriotomo I, Liang J, Feinstein DL, Vemuganti R(2007) Peroxisome proliferator-activated receptor-? agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. J Neurochem101:41-56.
- Yan Y, Sailor K, Lang B, Park SW, Vemuganti R, Dempsey RJ (2007) MCP1 plays a critical role in neuroblast migration following focal cerebral ischemia. J Cereb Blood Flow Metab 27:1213-1224.
- Yi JH, Park SW, Kapadia R, Vemuganti R (2007) Role of transcription factors in mediating post-ischemic cerebral inflammation and brain damage: A review.Neurochem Int 50:1014-1027.
- Wiltrout C, Lang B, Yan Y, Dempsey RJ, Vemuganti R (2007) Repairing brain after stroke: A review on post-ischemic neurogensis. Neurochem Int 50:1028-1041.
- Park S, Yi J, Satriotomo I, Miranpuri G, Bowen K, Resnick DK, Vemuganti R (2007) Treatment with PPAR-g ligands decrease spinal cord injury induced neuronal damage, apoptosis, neurological dysfunction and inflammation. J Pharm Exp Therap 320:1002-1012.
- Kapadia R, Tureyen K, Bowen KK, Kalluri H, Johnson PF, Vemuganti R (2006) Decreased brain damage and curtailed inflammation in transcription factor C/EBP-ß knockout mice following transient focal cerebral ischemia. J Neurochem98:1718-1731