Blood-Brain Barrier Disruption and Its Involvement in Neurodevelopmental and Neurodegenerative Disorders

Int J Mol Sci. 2022 Dec 3;23(23):15271. doi: 10.3390/ijms232315271.

Abstract

The blood-brain barrier (BBB) is a highly specialized and dynamic compartment which regulates the uptake of molecules and solutes from the blood. The relevance of the maintenance of a healthy BBB underpinning disease prevention as well as the main pathomechanisms affecting BBB function will be detailed in this review. Barrier disruption is a common aspect in both neurodegenerative diseases, such as amyotrophic lateral sclerosis, and neurodevelopmental diseases, including autism spectrum disorders. Throughout this review, conditions altering the BBB during the earliest and latest stages of life will be discussed, revealing common factors involved. Due to the barrier's role in protecting the brain from exogenous components and xenobiotics, drug delivery across the BBB is challenging. Potential therapies based on the BBB properties as molecular Trojan horses, among others, will be reviewed, as well as innovative treatments such as stem cell therapies. Additionally, due to the microbiome influence on the normal function of the brain, microflora modulation strategies will be discussed. Finally, future research directions are highlighted to address the current gaps in the literature, emphasizing the idea that common therapies for both neurodevelopmental and neurodegenerative pathologies exist.

Keywords: blood–brain barrier; neurodegeneration; neurodevelopment; therapies.

Publication types

  • Review

MeSH terms

  • Biological Transport
  • Blood-Brain Barrier* / pathology
  • Brain / pathology
  • Drug Delivery Systems
  • Humans
  • Neurodegenerative Diseases* / pathology