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Updated: Aug 13, 2026
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 attenuates white matter damage in a rat model of chronic cerebral hypoperfusion
Kyung-Ok Cho1, Hyen O La, Young-Jin Cho
1Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Abstract:
White matter lesions are thought to result from chronic cerebral ischemia and constitute a core pathology of subcortical vascular dementia. This rarefaction has been known to be associated with microglial activation. We investigated whether minocycline, a microglial inhibitor, attenuates the white matter damage induced by chronic cerebral hypoperfusion that is used as a model of vascular dementia. Male Wistar rats were subjected to bilateral, permanent occlusion of the common carotid arteries (BCCAO) to induce chronic cerebral hypoperfusion. Minocycline or saline was injected daily for 2 weeks after BCCAO. In the corpus callosum and the optic tract, white matter damage observed with Klüver-Barrera staining was significantly attenuated in the minocycline-treated group compared to saline-treated controls. In control rats, immunoreactivities of major basic protein (MBP), Ox-42 as a microglial marker, and matrix metalloproteinase (MMP)-2 were increased in the corpus callosum. Minocycline significantly reduced these changes. Co-expression of Ox-42 and MMP-2 was confirmed by double immunofluorescence histochemistry. Our results suggest that chronic treatment with minocycline could be protective against at least some ischemic white matter damage, and its mechanism may be related to suppressing microglial activation.
Insights
Minocycline, a microglial inhibitor, reduced white matter damage in a rat model of vascular dementia. This suggests minocycline may protect against ischemic white matter injury by suppressing microglial activation.
Area of Science:
- Neuroscience
- Neurology
- Pathology
Background:
- White matter lesions are linked to chronic cerebral ischemia and subcortical vascular dementia.
- Microglial activation is associated with white matter rarefaction in vascular dementia models.
Purpose of the Study:
- To investigate if minocycline, a microglial inhibitor, can mitigate white matter damage caused by chronic cerebral hypoperfusion.
- To explore the potential of minocycline as a therapeutic agent for vascular dementia.
Main Methods:
- Male Wistar rats underwent bilateral common carotid artery occlusion (BCCAO) to model chronic cerebral hypoperfusion.
- Minocycline or saline was administered daily for two weeks post-BCCAO.
- White matter damage was assessed using Klüver-Barrera staining, and microglial activation markers (Ox-42) and matrix metalloproteinase-2 (MMP-2) were quantified.
Main Results:
- Minocycline treatment significantly attenuated white matter damage in the corpus callosum and optic tract.
- Minocycline reduced the increased immunoreactivity of major basic protein (MBP), Ox-42, and MMP-2 in the corpus callosum.
- Double immunofluorescence confirmed co-expression of Ox-42 and MMP-2, indicating microglial involvement in damage.
Conclusions:
- Chronic minocycline treatment offers protection against ischemic white matter damage in a vascular dementia model.
- The protective mechanism of minocycline appears to involve the suppression of microglial activation.
