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Transport of microperoxidase across segments of cerebral arterioles under normal conditions
Abstract:
Microperoxidase, injected intravenously into mice, was allowed to circulate in the blood stream for 1 min to 1 h. The amount of reaction product in the walls of cerebral arterioles was most pronounced after circulation of 40 mg peroxidase for one min, the maximum dose used. The peroxidase was transported across the endothelium in a few segments of cerebral arterioles, lying on the surface of the brain or restricted to regions of the brain parenchyma. Reaction product was observed in vesicles: 1 open to the vessel lumen, 2 freely situated in the cytoplasm of endothelial cells, and 3 open to the subendothelial basement membrane. The endothelial cells did not show leaky plasma membranes. Channels or chains or vesicles, simultaneously open to the vessel lumen and the subendothelial basement membrane, were not seen, nor were fenestrae found. Furthermore, reaction product never formed a continuous column from the first luminal to the first abluminal tight junctions between two adjacent endothelial cells. From these observations, it is suggested that vesicular transfer of intravenously injected microperoxidase may occur under normal conditions across the endothelium in segments of cerebral arterioles.
Insights
Intravenously injected microperoxidase crosses the cerebral arteriole endothelium via vesicular transport in mice. This process occurs under normal conditions, suggesting a pathway for molecule movement across the blood-brain barrier.
Area of Science:
- Neuroscience
- Cell Biology
- Vascular Biology
Background:
- The blood-brain barrier (BBB) restricts the passage of molecules into the brain.
- Understanding transport mechanisms across cerebral endothelium is crucial for drug delivery and neurological research.
Purpose of the Study:
- To investigate the transport pathway of microperoxidase across the cerebral arteriole endothelium in vivo.
- To determine if microperoxidase crosses the endothelium via vesicular transport under normal physiological conditions.
Main Methods:
- Intravenous injection of microperoxidase into mice.
- Analysis of reaction product localization within cerebral arteriole walls at various time points (1 min to 1 h).
- Microscopic examination of endothelial cell structure and vesicular transport.
Main Results:
- Microperoxidase reaction product was observed within endothelial vesicles, open to the lumen, within the cytoplasm, and open to the subendothelial basement membrane.
- No evidence of leaky plasma membranes, fenestrae, or continuous channels across the endothelium was found.
- Maximum transport occurred with a high dose (40 mg) and short circulation time (1 min).
Conclusions:
- Vesicular transport is a likely mechanism for microperoxidase crossing the cerebral arteriole endothelium.
- This suggests a potential pathway for macromolecule transport across the BBB under normal conditions.