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Magnesium plus mexiletine inhibit energy usage and protect retinas against ischemia
K I Maynard1, A Quiñones-Hinojosa, C S Ogilvy
1Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Abstract:
We determined whether exogenous Mg2+ and/or mexiletine (Mex), which are reported to be neuroprotective agents, reduced neuronal energy requirements and protected against ischemia, using isolated rabbit retinas. Under non-ischemic conditions, Mex (300 microM) and the combination of Mg2+ (1 mM) plus Mex (300 microM) significantly reduced glucose utilization, by 19% and 31%, respectively. The combination of Mg2+ plus Mex, but not either agent alone, significantly reduced lactate production (by 18%; p < 0.05). When added during 2 h of ischemia (simulated by the reduction of oxygen from 95% to 15% and of glucose from 6 mM to 1 mM), Mg2+ plus Mex improved the recovery of glucose utilization (p < 0.01), lactate production (p < 0.05) and neuronal function (p < 0.05) for 3 h following return to control (post-ischemia/recovery) conditions. Thus reducing energy demands by blocking functions during temporary ischemia, protects neurons from irreversible functional damage.
Insights
Magnesium (Mg2+) and mexiletine (Mex) reduce neuronal energy demands. This combination protects rabbit retinas from ischemic damage by lowering energy requirements during ischemia.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Exogenous magnesium (Mg2+) and mexiletine (Mex) are recognized for their neuroprotective properties.
- Understanding their impact on neuronal energy metabolism is crucial for developing effective ischemia treatments.
Purpose of the Study:
- To investigate the effects of Mg2+ and Mex on neuronal energy requirements in isolated rabbit retinas.
- To determine if these agents protect against ischemic damage by modulating energy metabolism.
Main Methods:
- Isolated rabbit retinas were used to assess glucose utilization and lactate production under non-ischemic and ischemic conditions.
- The effects of Mg2+ and Mex, alone and in combination, were evaluated before, during, and after simulated ischemia.
Main Results:
- Mex and the Mg2+ plus Mex combination significantly reduced glucose utilization under non-ischemic conditions.
- The Mg2+ plus Mex combination reduced lactate production, indicating decreased metabolic activity.
- During ischemia, Mg2+ plus Mex improved the recovery of glucose utilization, lactate production, and neuronal function post-ischemia.
Conclusions:
- Reducing neuronal energy demands by blocking functions during temporary ischemia confers protection against irreversible functional damage.
- The combination of Mg2+ and Mex shows significant potential in mitigating ischemic neuronal injury by modulating energy metabolism.