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A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Minocycline treatment reduces white matter damage after excitotoxic striatal injury
Joanilson S Guimarães1, Marco Aurelio M Freire, Rafael R Lima
1Edmond and Lily Safra International Institute of Neuroscience of Natal, Natal/RN, Brazil.
Abstract:
We investigated the protective effects of minocycline following white matter damage (WMD) in the rat striatum. Excitotoxic lesions were induced by N-Methyl-d-Aspartate (NMDA) microinjections and caused striatal damage, concomitant with microglial/macrophage activation. The excitotoxic lesion both damaged oligodendrocytes (Tau-1(+) cells) and caused a decrease in tissue reactivity for myelin basic protein (MBP) after post-lesional day 3 (PLD). Treatment with the semi-synthetic tetracycline antibiotic minocycline, however, led to oligodendrocyte preservation and decreased myelin impairment. Taken together, these results suggest that white matter damage (WMD) is an important component of the physiopathology of acute striatal damage and that microglial/macrophage activation contributes to this pathological phenomenon.
Insights
Minocycline protects white matter damage (WMD) in rat striatum following excitotoxic lesions. This antibiotic preserves oligodendrocytes and reduces myelin impairment, suggesting a role in mitigating neuroinflammation.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- White matter damage (WMD) is a key component of acute striatal injury.
- Microglial and macrophage activation are implicated in the pathology of WMD.
- Oligodendrocyte damage and myelin loss are consequences of excitotoxic insults.
Purpose of the Study:
- To investigate the neuroprotective effects of minocycline in a rat model of striatal excitotoxic injury.
- To determine if minocycline can mitigate white matter damage and associated cellular pathology.
Main Methods:
- Induction of excitotoxic lesions in the rat striatum using N-Methyl-d-Aspartate (NMDA) microinjections.
- Administration of minocycline post-lesion.
- Assessment of oligodendrocyte integrity (Tau-1 staining) and myelin basic protein (MBP) reactivity.
Main Results:
- NMDA lesions caused significant striatal damage, oligodendrocyte loss, and reduced MBP reactivity.
- Minocycline treatment preserved oligodendrocytes (Tau-1 positive cells).
- Minocycline treatment reduced myelin impairment, as indicated by MBP reactivity.
Conclusions:
- White matter damage is a significant pathological feature of acute striatal injury.
- Microglial/macrophage activation contributes to white matter damage in this model.
- Minocycline exhibits neuroprotective effects by preserving white matter integrity and reducing myelin loss.
