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. 2022 Jan 15:366:109406.
doi: 10.1016/j.jneumeth.2021.109406. Epub 2021 Nov 9.

Severe acute neurotoxicity reflects absolute intra-carotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine dose in non-human primates

S A Norris  1 , Hcb White  2 , A Tanenbaum  2 , E L Williams  2 , C Cruchaga  3 , L Tian  2 , R E Schmidt  4 , J S Perlmutter  5
Affiliations

Severe acute neurotoxicity reflects absolute intra-carotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine dose in non-human primates

S A Norris et al. J Neurosci Methods. .
No abstract available

Keywords: Basal ganglia; MPTP; Monkey; Neurotoxicity; Striatum.

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Conflict of interest statement

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1.
Fig. 1.
Gross brain pathology 10 h post-MPTP from the same animal. Sections demonstrate an anterior striatal coronal section (top = superior, bottom = inferior brain) for A) right (MPTP infused) striatum and B) left (no MPTP) striatum. White arrows indicate regions of MPTP infused striatum with striatal edema associated with softening when palpated.
Fig. 2.
Fig. 2.
Hematoxylin and Eosin staining in a single animal (MMo) 5.5 h following MPTP administration (A-C): A) whole mount image of basal ganglia and adjacent cortex with pale basal ganglia lesions (arrows); B) 4X magnification, lesion margin with normal tissue (arrows demarcate separation), C) 20X magnification, junction of normal cortex (left, blue arrow) and neurons undergoing esosinophilic neuronal necrosis (right, red arrow). These abnormalities are greater than expected 5.5 h following acute ischemic stroke, thus representing toxic injury; D-F) Similar images for a separate animal (MJe) 3.25 h following iatrogenic ischemic stroke demonstrating normal histology as would be anticipated in this time period.
Fig. 3.
Fig. 3.
MPTP dosing strategy and immediate post-procedural recovery. A) Absolute MPTP dose is significantly different in animals with acute recovery versus severe acute neurotoxicity. B) Weight-based MPTP dose is not significantly different across the same outcomes.
Fig. 4.
Fig. 4.
A) scatter plots of brain volume for both MPTP outcome groups. Horizontal bars represent mean brain volumes which do not differ between groups. Scatterplots of B) brain volume versus absolute dose, C) brain volume versus weight, and D) animal weight versus age with independent linear fits for recovery (solid line) and severe neurotoxicity (dashed line) groups.
See this image and copyright information in PMC

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