MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys(778 views) Miletich RS, Bankiewicz KS, Quarantelli M, Plunkett RJ, Frank J, Kopin IJ, Di Chiro G
Ann Neurol (ISSN: 0364-5134), 1994 Jun; 35(6): 689-697.
Affiliations: Neuroimaging Branch, Natl. Inst. Neurol. Disord. Stroke, Bethesda, MD, United States
Surgical Neurology Branch, Natl. Inst. Neurol. Disord. Stroke, Bethesda, MD, United States
Lab. of Diagn. Radiology Research, National Institutes of Health, Bethesda, MD, United States
Clinical Neurosciences Branch, Natl. Inst. Neurol. Disord. Stroke, Bethesda, MD, United States
References: Not available.
MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys
Exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can cause an acute chemical toxicity resulting in a parkinsonian state in humans and nonhuman primates. We wished to assess whether the toxicity from MPTP is associated with changes on magnetic resonance images of brain structures containing dopamine neuronal processes or with disrupture of the blood-brain barrier. Normal rhesus monkeys and monkeys at various times after being subjected to unilateral intracarotid injection of MPTP (0.4 mg/kg) were studied with magnetic resonance imaging using T1- and T2-weighted spin-echo and gradient-echo sequences. Disrupture of the blood-brain barrier was assessed also with magnetic resonance imaging after administration of gadolinium-diethylenetriamine pentaacetic acid. Parkinsonian symptoms contralateral to the infused carotid usually appeared within 1 day after MPTP exposure, reaching their peak severity by 7 days, when all monkeys showed clear clinical abnormalities. Magnetic resonance imaging changes developed in concomitance with the clinical signs and were characterized by increased signal intensity on T2-weighted images as well as decreased intensity on T1- weighted images of the ipsilateral caudate and putamen. T2 hyperintensity was also present just dorsal to the pars compacta of the substantia nigra, in the region of the proximal nigrostriatal tract. All magnetic resonance imaging changes dissipated in the next 2 weeks. There were no abnormalities at any time in the globus pallidus, nucleus accumbens, and other structures innervated by the mesocorticolimbic dopamine system. After MPTP exposure, there was no evidence of blood-brain barrier disrupture, suggesting that vasogenic edema was an unlikely factor in the production of the observed abnormalities. The signal intensity changes on magnetic resonance images are most probably associated with cytotoxic edema caused by the acute MPTP- induced degeneration of nigrostriatal dopamine nerve terminals and axons. Follow-up by magnetic resonance imaging, to 3 years after MPTP infusion, failed to reveal any residual abnormalities.
MRI detects acute degeneration of the nigrostriatal dopamine system after MPTP exposure in hemiparkinsonian monkeys
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(535 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote