Barriers in the developing brain and Neurotoxicology.
C Joakim Ek1, Katarzyna M Dziegielewska, Mark D Habgood
1Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010, Australia.
Neurotoxicology
|December 27, 2011
Summary
Brain barriers, including the blood-brain barrier and blood-cerebrospinal fluid barrier, are effective early in development. These crucial barriers protect the developing brain from harmful substances and are vital for clinical applications.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- The developing brain requires a controlled internal environment maintained by brain barriers.
- Key barriers include the blood-brain barrier (BBB) and blood-cerebrospinal fluid (Blood-CSF) barrier.
- Tight junctions are essential for the integrity of these barriers.
Purpose of the Study:
- To review historical and recent evidence on the effectiveness of embryonic and neonatal brain barriers.
- To contrast established barrier function with the misconception of immature or absent barriers in early development.
- To emphasize the importance of understanding barrier function for clinical management and drug safety.
Main Methods:
- Review of morphological, biochemical, and molecular data.
- Analysis of historical evidence on barrier mechanisms.
- Examination of gene expression and physiological transport data.
Main Results:
- Tight junctions in endothelial and epithelial cells are effective upon differentiation.
- Many transport mechanisms are present and more active in the developing brain than in adults.
- Gene expression for some transporters is significantly higher in embryos compared to adults.
Conclusions:
- Brain barrier mechanisms are functionally effective from early development.
- The belief that 'the' blood-brain barrier is immature in newborns is challenged by substantial evidence.
- Accurate knowledge of barrier function is critical for drug development and clinical care in pregnancy and neonates.
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