Evaluation of Early and Prolonged Effects of Acute Neurotoxicity and Neuroprotection Using Novel Functional Imaging Techniques
Abstract
We have explored efficacy of neuroprotection on functional and metabolic pathways in transgenic mouse model and 3-nitropropionic acid induced rat model of Huntington's disease. We conducted longitudinal studies of glucose utilization (energy metabolism) in transgenic mice during the treatment with transglutaminase inhibitor cystamine using 4 different doses; 5/4, 9, 50 and 100 mg/kg ip. In addition, we used CPCCOEt, an antagonist for mGluR 1 receptors with a dose of 5.2-mg/kg. each group of mice had an untreated control group for the parallel imaging studies. In these studies were found that neuroprotection for energy metabolism can be obtained even with a low dose of 5.4 mg/kg. This confirmed also by MRS studies of NAA and the endpoint histological evaluation. However, to protect dopaminergic system a higher dose of cystamine (>50 mg/kg ip.) was required. CPCCOEt with a dose of 5.2 mg/kg ip. Provided neuroprotection for energy metabolism at the same levels as cystamine with 9 mg/kg ip. In 3-NP rat model we found that pretreatment with cystamine (9 mg/kg ip.) before acute administration of 3-NP (25 mg/kg iv.) will significantly enhance 3-NP induced neurotoxicity in rats. This conclusion is based on studies of glucose metabolism, behavior, enhanced mortality and endpoint histological studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2003
- Accession Number
- ADA419492
Entities
People
- Anna-Liisa Brownell
Organizations
- Massachusetts General Hospital