Raghu Vemuganti

 

 

Molecular Mechanisms of Inflammation, Neuronal Death, and Neurogenesis After Stroke

Email: vemugant@neurosurg.wisc.edu

Office Phone: (608) 263-4055, (608) 262-6080

Research Strengths: Development: Plasticity and Repair, Molecular Neuroscience, Neurobiology of Disease

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.

Selected Publications:

• Vemuganti, R., R.J. Dempsey, and K.K. Bowen. 2004. Inhibition of ICAM-1 expression by antisense oligonucleotides is neuroprotective after middle cerebral artery occlusion. Stroke 35: 179-184.
• Dhodda, V.K., K.A. Sailor, K.K. Bowen and R. Vemuganti. 2004. Putative endogenous mediators of preconditioning-induced ischemic tolerance in rat brain identified by genomic and proteomic analysis. J. Neurochem. 89: 73-89.
• Dempsey, R.J., K.A. Sailor, K.K. Bowen, K. Tureyen, R.Vemuganti. 2003. Stroke-induced progenitor cell proliferation in adult spontaneously hypertensive rat brain: Effect of exogenous IGF-1 and GDNF. J. Neurochem. 87: 586-597.
• Vemuganti, R., A. Dogan, K.G. Todd, K.K. Bowen, B-T. Kim, J.D. Rothstein, and R.J. Dempsey. 2001. Antisense knockdown of the glial glutamate transporter GLT-1, but not neuronal glutamate transporter EAAC1, exacerbates focal cerebral ischemia-induced neuronal damage. J. Neurosci. 21: 1876-1883.
• Vemuganti, R., A. Dogan, A. Rao, K.K. Bowen, J. Hatcher, and R.J. Dempsey. 2001. Knockdown of ODC exacerbates ischemic neuronal damage. J. Cereb. Blood Flow Metab. 21: 945-954.