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| Grant Number: | 1R43NS043013-01 |
| PI Name: | MULCHAHEY, JAMES J. |
| PI Email: | jmulchahey@phase2d.com |
| PI Title: | ASSISTANT PROFESSOR |
| Project Title: | Biomarker of Neurotoxicity in Meningitis |
Abstract: DESCRIPTION (provided by applicant): The objective of this Phase I application is to develop a sensitive biomarker for quantifying neurotoxicity and neuroprotectant efficacy in meningitis. Previous research documents that brain injury caused by meningitis affects multiple brain areas with a heterogeneous distribution. We have previously shown that the cytoskeletal protein MAP-tau is cleavedin brain during axonal degeneration. We developed a sensitive ELISA that specifically quantifies this biomarker of neuronal degeneration, cleaved-tau (C-tau). Our preliminary studies demonstrate that levels of C-tau are increased over 300-fold in an animal model of group B streptococcus meningitis (GBM). We will use the well-documented neurotoxicity of GBM to validate the C-tau as a biomarker of neurotoxicity and a measure of neuroprotectant efficacy. Our Specific Aims are: Specific Aim 1: Determine whether GBM results in a time-dependent elevation in brain, plasma and CSF concentrations of C-tau. Specific Aim 2: Determine it C-tau levels in brain, CSF and plasma correlate with traditional measures of neuronal damage in GBM. Specific Aim 3: Determine whether perihperal tissues such as liver, kidney or spleen are potential sources of C-tau measured in GBM. Specific Aim 4: Determine whether a neuroprotectant intervention known to be effective in GBM has predictable effects on C-tau levels. PROPOSED COMMERCIAL APPLICATIONS: The C-tau ELISA may be used to quantify the severity of brain injury in meningitis and to quantify the effects of neuroprotectant interventions in basic science, preclinical and clinical research settings.
Thesaurus Terms:
Streptococcus agalactiae, bacterial protein, biomarker, enzyme linked immunosorbent assay, meningitis, neuroprotectant, neurotoxicology, technology /technique development
microtubule associated protein, neural degeneration
laboratory rat
| Institution: | PHASE TWO DISCOVERY, INC. |
| 3130 HIGHLAND AVE, 3RD FL | |
| CINCINNATI, OH 45219 | |
| Fiscal Year: | 2002 |
| Department: | |
| Project Start: | 01-AUG-2002 |
| Project End: | 31-JAN-2003 |
| ICD: | NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE |
| IRG: | ZRG1 |