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Improved Method for the Preparation of a Human Cell-based, Contact Model of the Blood-Brain Barrier
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Streptozotocin Causes Blood-Brain Barrier and Astrocytic Dysfunction In Vitro.

Sarah A Habib1,2,3, Mohamed M Kamal2,3,4, Mohamed H Aly2,3,5

  • 1Biochemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.

Cells
|November 13, 2025
PubMed
Summary
This summary is machine-generated.

Streptozotocin (STZ) directly damages brain endothelial cells and astrocytes, disrupting the blood-brain barrier (BBB). This study reveals STZ

Keywords:
GLUT-1Streptozotocinastrocytesblood–brain barrierbrain endothelial cellstight junctions

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Toxicology

Background:

  • Streptozotocin (STZ) is an alkylating agent used to model Alzheimer's disease features, but its neurotoxicity mechanisms remain unclear.
  • The blood-brain barrier (BBB), formed by brain endothelial cells and supported by astrocytes, is crucial for brain function.

Purpose of the Study:

  • To investigate the direct effects of STZ on human brain endothelial-like cells (iBECs) and primary human astrocytes.
  • To determine if STZ-induced damage to these cells contributes to its neurotoxic effects and BBB disruption.

Main Methods:

  • Cultured human iPSC-derived iBECs to create an in vitro BBB model.
  • Treated iBECs and primary human astrocytes with 5 mM STZ.
  • Assessed BBB integrity using transendothelial electrical resistance (TEER) and albumin leakage.
  • Evaluated cell morphology, tight junction proteins, GLUT-1 expression, and cell viability.

Main Results:

  • STZ treatment (5 mM) induced delayed BBB leakage in iBECs, evidenced by reduced TEER and increased albumin permeability.
  • STZ altered iBEC morphology, decreased tight junction proteins and GLUT-1 expression, and reduced iBEC numbers.
  • STZ reduced GFAP signal and cell numbers in astrocytes, indicating anti-proliferative and/or toxic effects.

Conclusions:

  • STZ directly damages brain endothelial cells, leading to BBB disruption.
  • STZ exhibits toxic effects on astrocytes.
  • These direct cellular toxicities likely contribute to the overall neurotoxic effects of STZ.