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Updated: Jun 29, 2026
Monitoring Astrocyte Reactivity and Proliferation in Vitro Under Ischemic-Like Conditions
Published on: October 21, 2017
Ultrastructural and temporal changes of the microvascular basement membrane and astrocyte interface following focal
Il Kwon1, Eun Hee Kim, Gregory J del Zoppo
1Department of Neurology, National Core Research Center for Nanomedical Technology, Yonsei University College of Medicine, Seoul, Korea.
Abstract:
Microvascular integrity is lost during cerebral ischemia. Detachment of the microvascular basement membrane (BM) from the astrocyte, as well as degradation of the BM, is responsible for the loss of microvascular integrity. However, their ultrastructural and temporal changes during cerebral ischemia are not well known. Male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) for 1, 4, 8, 12, 16, 20, and 48 hr. By using transmission electron microscopy, the proportion of intact BM-astrocyte contacts and electron densities of the BM were measured from five randomly selected microvessels in the ischemic basal ganglia. Their temporal changes and associations with activities of the matrix metalloproteinases (MMPs) were investigated. The intact portion of the BM-astrocyte contacts was decreased significantly within 4 hr and was rarely observed at 48 hr after MCAO. Decreases in the electron density and degradation of the BM were significant 12 hr after MCAO. The intact BM-astrocyte contacts and the mean BM density showed a significant positive correlation (r = 0.784, P < 0.001). MMP-9 activity was correlated negatively with the intact BM-astrocyte contacts (r = -0.711, P < 0.001) and with the BM density (r = -0.538, P = 0.0016). The increase in MMP-9 coincided temporally with the loss of the BM-astrocyte contacts and a decrease in the BM density. Ultrastructural alterations occurring in the microvascular BM and its contacts with astrocyte endfeet were temporally associated in cerebral ischemia. Time courses of their alterations should be considered in the treatment targeted to the microvascular BM and its contact with astrocytes.
Insights
Cerebral ischemia damages microvascular integrity by detaching and degrading the basement membrane (BM) from astrocytes. Matrix metalloproteinase-9 (MMP-9) activity increases, correlating with BM damage and loss of astrocyte contact, highlighting temporal changes crucial for treatment.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Microvascular integrity is crucial for brain function and is compromised during cerebral ischemia.
- The detachment and degradation of the microvascular basement membrane (BM) from astrocytes contribute to this loss of integrity.
- The precise ultrastructural and temporal changes of the BM-astrocyte interface during ischemia are not fully understood.
Purpose of the Study:
- To investigate the ultrastructural and temporal changes of microvascular basement membrane (BM)-astrocyte contacts during cerebral ischemia.
- To examine the degradation of the BM and its association with matrix metalloproteinase (MMP) activity.
- To establish the temporal relationship between BM integrity, astrocyte contact, and MMPs in an ischemic stroke model.
Main Methods:
- Male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (MCAO) for durations of 1 to 48 hours.
- Transmission electron microscopy was used to assess intact BM-astrocyte contacts and BM electron density in the ischemic basal ganglia.
- Matrix metalloproteinase-9 (MMP-9) activity was measured and correlated with ultrastructural changes.
Main Results:
- Intact BM-astrocyte contacts significantly decreased within 4 hours post-MCAO, becoming rare by 48 hours.
- BM electron density and integrity showed significant degradation starting 12 hours after MCAO.
- MMP-9 activity increased, correlating negatively with intact BM-astrocyte contacts and BM density, indicating its role in BM damage.
Conclusions:
- Ultrastructural alterations in the microvascular BM and its astrocyte contacts are temporally associated during cerebral ischemia.
- The loss of BM-astrocyte contacts precedes significant BM degradation.
- Understanding the time course of these microvascular changes is essential for developing targeted therapeutic strategies for ischemic stroke.
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