title: Rasagiline prevents neurodegeneration in thiamine deficient rats-a longitudinal MRI study.
abstract: Neuroprotection is a therapeutic approach for the management of neurodegenerative diseases. Experimental thiamine deficiency (TD) in rats provides a model for selective neurodegeneration accompanied by chronic oxidative deficits. Rats exhibit neurological and cognitive impairments, which can be partially reversed by thiamine administration, enabling the study of mechanisms of neurodegeneration as well as neuroprotection. In this magnetic resonance (MR) study we used various techniques to characterize the neuroprotective effects of rasagiline, a selective MAO-B inhibitor. TD was induced by a thiamine-deficient diet and daily injections of the central thiamine antagonist, pyrithiamine. Daily injections of either saline or rasagiline (3mg/kg) were also administered to untreated-TD rats and rasagiline-treated TD rats respectively. With the appearance of neurological symptoms, all injections were terminated and thiamine was restored. MRI scans were performed before induction of TD (control values), on days 10, 12 (before symptoms appear), 14 (symptomatic stage) and during the recuperation period. Both groups were assessed using in-vivo serial T2-weighted imaging and diffusion tensor imaging (DTI), from which apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated. A histopathological evaluation was correlated with the MRI analysis. Thalamic hyperintensities were significantly smaller and less severe in the rasagiline-treated TD rats. Enlargement of the lateral ventricles was significantly less pronounced in the rasagiline-treated TD group. FA values of the untreated-TD group decreased significantly in the thalamic on days 12 and 14 and in the corpus callosum on day 14. These results demonstrate significant neuroprotection by rasagiline which could have implications for clinical neurodegenerative disorders.
authors: Tel Aviv University, Department of Physiology & Pharmacolgy, Sackler School of Medicine, Pob 39040, 69978 Ramat Aviv, Israel.
authors: Vered
authors: V
authors: Dror
authors: Tel Aviv University, Department of Physiology & Pharmacolgy, Sackler School of Medicine, Pob 39040, 69978 Ramat Aviv, Israel.
authors: Moshe
authors: M
authors: Rehavi
authors: Department of Chemical Research Support MR Center, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Inbal E
authors: IE
authors: Biton
authors: Tel Aviv University, Department of Physiology & Pharmacolgy, Sackler School of Medicine, Pob 39040, 69978 Ramat Aviv, Israel. Electronic address: seliash@post.tau.ac.il.
authors: Sarah
authors: S
authors: Eliash
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D018450:Disease Progression; D007189:Indans / Q000494:pharmacology*; D053208:Kaplan-Meier Estimate; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009929:Organ Size; D011745:Pyrithiamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000187:drug effects / Q000473:pathology; D013832:Thiamine Deficiency / Q000150:complications / Q000188:drug therapy* / Q000473:pathology
chemical_list: D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; C031967:rasagiline; D011745:Pyrithiamine
keywords: Magnetic resonance imaging; Neurodegeneration; Neuroprotection; Rasagiline; Thiamine deficiency