The blood-brain barrier effectively shields the brain parenchyma from a number of potentially neurotoxic substances. This is achieved in virtue of expression of specific zipper-like proteins that join neighboring endothelial cells. In addition to this cellular barrier, endothelial cells also express multiple drug resistance (MDR)-related proteins that act as extruders of a number of drugs that would otherwise significantly contribute to treatment of a number of central nervous system disorders including epilepsy. We have shown upregulation of MDR gene expression in endothelial cells isolated from human epileptic vs. non-epileptic brain. We have also unveiled an abnormal pattern of MDR expression in 1 """"""""epileptic"""""""" glia. To further our knowledge on the mechanisms involved in the development of pharmacoresistance to antiepileptic drugs (AED) we propose: 1) To study patterns of MDR gene expression across different epileptic pathologies compared to non-epileptic brain; 2) To determine the cellular distribution of MDR gene products in epileptic compared to non-epileptic cortex; 3) To test the hypothesis that breakdown of the blood-brain barrier is an early event leading to pharmacoresistance and expression of MDR in perivascular glia; and 4) To determine the AED permeability across and """"""""epileptic"""""""" blood-brain barrier model compared to non-MDR expressing endothelial cells and glia. We propose to use a multidisciplinary approach combining molecular biology, protein analysis and functional studies; these studies will be performed on freshly isolated surgical specimens characterized by their epileptogenic (or normal) electrical activity by a team of neurosurgeons and neurologists. The long-term goal of this laboratory is to understand interactions between neuronal and non-neuronal cells in health and disease. In particular, we are investigating how changes in blood-brain barrier function may drive glia and neurons into an """"""""epileptic"""""""" phenotype.
| Choi, Humberto; Puvenna, Vikram; Brennan, Chanda et al. (2016) S100B and S100B autoantibody as biomarkers for early detection of brain metastases in lung cancer. Transl Lung Cancer Res 5:413-9 |
| Dadas, Aaron; Washington, Jolewis; Marchi, Nicola et al. (2016) Improving the clinical management of traumatic brain injury through the pharmacokinetic modeling of peripheral blood biomarkers. Fluids Barriers CNS 13:21 |
| Ghosh, Chaitali; Hossain, Mohammed; Solanki, Jesal et al. (2016) Pathophysiological implications of neurovascular P450 in brain disorders. Drug Discov Today 21:1609-1619 |
| Puvenna, Vikram; Engeler, Madeline; Banjara, Manoj et al. (2016) Is phosphorylated tau unique to chronic traumatic encephalopathy? Phosphorylated tau in epileptic brain and chronic traumatic encephalopathy. Brain Res 1630:225-40 |
| Falcone, Tatiana; Carlton, Erin; Lee, Catherine et al. (2015) Does Systemic Inflammation Play a Role in Pediatric Psychosis? Clin Schizophr Relat Psychoses 9:65-78B |
| Ghosh, Chaitali; Hossain, Mohammad; Spriggs, Addison et al. (2015) Sertraline-induced potentiation of the CYP3A4-dependent neurotoxicity of carbamazepine: an in vitro study. Epilepsia 56:439-49 |
| Falcone, Tatiana; Janigro, Damir; Lovell, Rachel et al. (2015) S100B blood levels and childhood trauma in adolescent inpatients. J Psychiatr Res 62:14-22 |
| Bargerstock, Erin; Puvenna, Vikram; Iffland, Philip et al. (2014) Is peripheral immunity regulated by blood-brain barrier permeability changes? PLoS One 9:e101477 |
| Marchi, Nicola; Granata, Tiziana; Janigro, Damir (2014) Inflammatory pathways of seizure disorders. Trends Neurosci 37:55-65 |
| Janigro, Damir; Walker, Matthew C (2014) What non-neuronal mechanisms should be studied to understand epileptic seizures? Adv Exp Med Biol 813:253-64 |
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