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In vivo detection of excitotoxicity by manganese-enhanced MRI: comparison with physiological stimulation
Oliviero L Gobbo1, Fanny Petit, Hirac Gurden
1School of Pharmacy and Pharmaceutical Sciences, and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
Abstract:
Manganese-enhanced MRI (MEMRI) is a powerful technique for the in vivo monitoring of brain function in animals. Manganese enters into cells through calcium channels, i.e., voltage-gated calcium channels and activated glutamate receptors (e.g., N-methyl-D-aspartate receptors). N-methyl-D-aspartate receptors are activated both in normal physiological and pathophysiological conditions. Consistent with these mechanisms, we showed that in the olfactory bulb, the MEMRI signal strongly increases when excitotoxic mechanisms are induced by an administration of a N-methyl-D-aspartate receptor agonist, quinolinate. We found that the intensity of the MEMRI signal in excitotoxic conditions is similar to the odor-evoked signal in normal physiological conditions. Finally, we showed that the dynamics of the MEMRI signal are determined by the early phase of manganese in the olfactory bulb. Overall, these data show that, in addition to physiological studies, MEMRI can be used as an in vivo method to follow-up the dynamics of excitotoxic events.
Insights
Manganese-enhanced MRI (MEMRI) can track brain activity by monitoring manganese uptake via calcium channels. This study shows MEMRI effectively detects excitotoxic events in the olfactory bulb, similar to normal physiological responses.
Area of Science:
- Neuroscience
- Medical Imaging
Background:
- Manganese-enhanced MRI (MEMRI) monitors in vivo brain function in animals.
- Manganese uptake occurs through calcium channels, including voltage-gated calcium channels and N-methyl-D-aspartate (NMDA) receptors.
- NMDA receptors are involved in both physiological and pathophysiological brain conditions.
Purpose of the Study:
- To investigate the utility of MEMRI for monitoring excitotoxic events in the olfactory bulb.
- To compare MEMRI signal intensity during excitotoxicity with normal physiological odor responses.
- To determine the factors influencing MEMRI signal dynamics in the olfactory bulb.
Main Methods:
- Induction of excitotoxicity in the olfactory bulb using the NMDA receptor agonist, quinolinate.
- In vivo monitoring of brain function using Manganese-enhanced MRI (MEMRI).
- Analysis of MEMRI signal intensity and dynamics in response to excitotoxic stimuli.
Main Results:
- MEMRI signal significantly increased in the olfactory bulb upon induction of excitotoxicity with quinolinate.
- The intensity of the MEMRI signal during excitotoxic conditions was comparable to odor-evoked signals under physiological conditions.
- The early phase of manganese uptake in the olfactory bulb dictates the MEMRI signal dynamics.
Conclusions:
- MEMRI is a viable in vivo technique for monitoring the dynamics of excitotoxic events.
- MEMRI can be used beyond physiological studies to track pathophysiological processes in the brain.
- The findings highlight MEMRI's potential for studying neurological disorders involving excitotoxicity.
