negative regulation of establishment of blood-brain barrier

Definition

Target type: biologicalprocess

Any process that decreases the rate, frequency or extent of the establishment of the blood-brain barrier, a selectively permeable structural and functional barrier that exists between the capillaries and the brain. [GOC:dph, GOC:tb]

The blood-brain barrier (BBB) is a highly selective barrier that protects the central nervous system (CNS) from harmful substances in the bloodstream. Formation and maintenance of this barrier is a complex process involving interactions between endothelial cells, pericytes, astrocytes, and microglia. Negative regulation of the BBB establishment refers to mechanisms that inhibit or dampen the formation of this barrier, thereby potentially increasing permeability and allowing for the passage of substances that would otherwise be restricted.

Several mechanisms contribute to the negative regulation of BBB establishment, including:

1. **Signaling pathways:**
- **TGF-β signaling:** Transforming growth factor-beta (TGF-β) signaling can negatively regulate BBB formation by suppressing tight junction formation and increasing permeability.
- **VEGF signaling:** Vascular endothelial growth factor (VEGF) can promote angiogenesis and increase BBB permeability, potentially disrupting barrier integrity.
- **TNF-α signaling:** Tumor necrosis factor-alpha (TNF-α) can trigger inflammation and disrupt the BBB, increasing permeability.

2. **Cell-cell interactions:**
- **Endothelial cell-pericyte interactions:** Disruptions in the communication between endothelial cells and pericytes can weaken the BBB and increase permeability.
- **Astrocyte-endothelial cell interactions:** Dysfunctional astrocytes can release factors that disrupt BBB integrity.
- **Microglia-endothelial cell interactions:** Activation of microglia, often triggered by inflammation, can lead to BBB dysfunction and increased permeability.

3. **Genetic factors:**
- **Mutations in genes involved in tight junction formation:** Mutations in genes that encode for tight junction proteins can compromise BBB integrity and increase permeability.
- **Mutations in genes that regulate vascular development:** Mutations in genes involved in vascular development can lead to abnormal BBB formation and increased permeability.

4. **Environmental factors:**
- **Infections:** Infections can trigger inflammatory responses that damage the BBB and increase permeability.
- **Toxins:** Exposure to toxins can disrupt BBB integrity and increase permeability.
- **Stress:** Chronic stress can lead to BBB dysfunction and increased permeability.

The negative regulation of BBB establishment can have significant implications for brain health. Increased permeability of the BBB can contribute to neuroinflammation, neurodegeneration, and the development of neurological disorders. Understanding the mechanisms involved in negative regulation of BBB establishment is crucial for developing strategies to protect the brain from damage and disease.'
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Proteins (2)

Compounds (69)