Abstract
Although manganese (Mn) can enhance brain tissues for improving magnetic resonance imaging (MRI) assessments, the underlying neural mechanisms of Mn detection remain unclear. In this study, we used Mn-enhanced MRI to test the hypothesis that different Mn entry routes and spatiotemporal Mn distributions can reflect different mechanisms of neural circuitry and neurodegeneration in normal and injured brains. Upon systemic administration, exogenous Mn exhibited varying transport rates and continuous redistribution across healthy rodent brain nuclei over a 2-week timeframe, whereas in rodents following photothrombotic cortical injury, transient middle cerebral artery occlusion, or neonatal hypoxic-ischemic brain injury, Mn preferentially accumulated in perilesional tissues expressing gliosis or oxidative stress within days. Intravitreal Mn administration to healthy rodents not only allowed tracing of primary visual pathways, but also enhanced the hippocampus and medial amygdala within a day, whereas partial transection of the optic nerve led to MRI detection of degrading anterograde Mn transport at the primary injury site and the perilesional tissues secondarily over 6 weeks. Taken together, our results indicate the different Mn transport dynamics across widespread projections in normal and diseased brains. Particularly, perilesional brain tissues may attract abnormal Mn accumulation and gradually reduce anterograde Mn transport via specific Mn entry routes.
Highlights
Glutamine synthetase, which is a glial specific enzyme for regulating extracellular glutamate and reducing glutamate excitotoxicity[5,6,7,8,9]
We evaluated the spatiotemporal profiles of Mn enhancement in 3 different types of cerebral ischemic injuries induced by photothrombotic cortical injury (PCI), transient middle cerebral artery occlusion, and neonatal hypoxic-ischemic (HI) injury, and confirmed the alterations in biochemical processes that occurred in the enhanced perilesional tissues using immunohistochemical markers
Upon systemic Mn administration to healthy adult rats, longitudinal T1-weighted magnetic resonance imaging (MRI) showed increased signal intensities to varying extents in both cortical and subcortical brain nuclei at Day 1 and Day 5 compared to pre-injection and Day 12 (Fig. 1)
Summary
Glutamine synthetase, which is a glial specific enzyme for regulating extracellular glutamate and reducing glutamate excitotoxicity[5,6,7,8,9]. Because of the complex properties of Mn, it remains unclear how Mn is transported dynamically in normal and injured brains, and how Mn accumulates and enhances different brain tissues for MRI detection. We hypothesize that Mn-enhanced MRI can indicate different mechanisms of brain circuitry and neurodegeneration by examining different Mn entry routes and the spatiotemporal Mn distributions across widespread projections in normal and injured brain tissues. Our results indicate that Mn-enhanced MRI can be an important in vivo technique for dynamically assessing the neural circuitry and degenerative events in localized regions across the brain. It may help characterize the pathophysiological properties of perilesional brain tissues via different routes of Mn entry
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