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Morphological changes in acute cerebral ischemia after occlusion and reperfusion in the rat
Y Nakagawa1, N Fujimoto, K Matsumoto
1Department of Neurosurgery, National Kagawa Children's Hospital, Japan.
Abstract:
Blood-brain barrier permeability was investigated in acute focal ischemia after MCA occlusion and reperfusion. Four kind of tracers were used: sodium fluorescein and ionic lanthanum as a small molecular tracer, and Evans blue and HRP as a macromolecular tracer. BBB permeability to the tracers was observed macroscopically and studied by electron microscopy. The MCA was dissected free and occluded by ligation with 10-0 monofilament nylon suture. In the reperfusion model, the nylon suture was cut and the occluded MCA was reopened. Diffuse fluorescein staining was noted in the ipsilateral cortex; however, there was no extravasation of Evans blue or HRP in the occlusion model. Ionic lanthanum was demonstrated in the interendothelial space, basement membrane, and extracellular space. In the reperfusion model, intense fluorescein staining and hemorrhagic infarction were observed. Remarkable extravasation of Evans blue and HRP was also revealed in the ischemic lesion. HRP was demonstrated in the basement membrane and around the neuropils. Ultrastructural findings suggested that small molecules such as sodium fluorescein and ionic lanthanum may pass through the entire interendothelial cleft into the extracellular space before leakage of the macromolecules in the acute ischemic stage. Between 30 to 60 min after MCA occlusion, cerebral edema may begin with an escape of water and ions through the tight junctions. Reperfusion of MCA in the acute stage of ischemia may lead to abnormal vascular permeability to macromolecules as a manifestation of severe damage to the BBB.
Insights
Investigating blood-brain barrier (BBB) permeability in acute ischemic stroke shows small molecules cross early. Reperfusion significantly increases BBB leakage of larger molecules, indicating severe damage.
Area of Science:
- Neuroscience
- Cerebrovascular Research
- Pathophysiology
Background:
- The blood-brain barrier (BBB) protects the central nervous system but its integrity in acute ischemic stroke is not fully understood.
- Investigating BBB permeability is crucial for understanding stroke pathophysiology and developing therapeutic strategies.
Purpose of the Study:
- To investigate blood-brain barrier permeability to small and large molecular tracers during acute focal cerebral ischemia and reperfusion.
- To determine the sequence of BBB breakdown following middle cerebral artery (MCA) occlusion.
Main Methods:
- Acute focal cerebral ischemia was induced by MCA occlusion and subsequent reperfusion in a rodent model.
- Small molecule tracers (sodium fluorescein, ionic lanthanum) and macromolecular tracers (Evans blue, HRP) were used.
- BBB permeability was assessed macroscopically and via electron microscopy.
Main Results:
- In the occlusion model, small molecules permeated the BBB, but macromolecules did not.
- Ionic lanthanum was found in the interendothelial space, basement membrane, and extracellular space.
- Reperfusion led to intense staining, hemorrhagic infarction, and significant extravasation of macromolecules (Evans blue, HRP) into the ischemic lesion.
Conclusions:
- Small molecules cross the BBB early in acute ischemia, followed by larger molecules during reperfusion.
- Reperfusion exacerbates BBB damage, leading to macromolecular leakage and potentially contributing to cerebral edema.
- These findings highlight the dynamic nature of BBB dysfunction in ischemic stroke.