PMID- 34834200
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211129
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 13
IP  - 11
DP  - 2021 Oct 26
TI  - Blood-Brain Barrier Dysfunction in CNS Disorders and Putative Therapeutic 
      Targets: An Overview.
LID - 10.3390/pharmaceutics13111779 [doi]
LID - 1779
AB  - The blood-brain barrier (BBB) is a fundamental component of the central nervous 
      system (CNS). Its functional and structural integrity is vital to maintain the 
      homeostasis of the brain microenvironment by controlling the passage of 
      substances and regulating the trafficking of immune cells between the blood and 
      the brain. The BBB is primarily composed of highly specialized microvascular 
      endothelial cells. These cells' special features and physiological properties are 
      acquired and maintained through the concerted effort of hemodynamic and cellular 
      cues from the surrounding environment. This complex multicellular system, 
      comprising endothelial cells, astrocytes, pericytes, and neurons, is known as the 
      neurovascular unit (NVU). The BBB strictly controls the transport of nutrients 
      and metabolites into brain parenchyma through a tightly regulated transport 
      system while limiting the access of potentially harmful substances via efflux 
      transcytosis and metabolic mechanisms. Not surprisingly, a disruption of the BBB 
      has been associated with the onset and/or progression of major neurological 
      disorders. Although the association between disease and BBB disruption is clear, 
      its nature is not always evident, specifically with regard to whether an impaired 
      BBB function results from the pathological condition or whether the BBB damage is 
      the primary pathogenic factor prodromal to the onset of the disease. In either 
      case, repairing the barrier could be a viable option for treating and/or reducing 
      the effects of CNS disorders. In this review, we describe the fundamental 
      structure and function of the BBB in both healthy and altered/diseased 
      conditions. Additionally, we provide an overview of the potential therapeutic 
      targets that could be leveraged to restore the integrity of the BBB concomitant 
      to the treatment of these brain disorders.
FAU - Archie, Sabrina Rahman
AU  - Archie SR
AD  - Department of Pharmaceutical Sciences, Texas Tech University Health Sciences 
      Center, Amarillo, TX 79106, USA.
FAU - Al Shoyaib, Abdullah
AU  - Al Shoyaib A
AD  - Department of Pharmaceutical Sciences, Texas Tech University Health Sciences 
      Center, Amarillo, TX 79106, USA.
FAU - Cucullo, Luca
AU  - Cucullo L
AUID- ORCID: 0000-0002-2827-7162
AD  - Department of Foundational Medical Studies, Oakland University William Beaumont 
      School of Medicine, Rochester, MI 48309, USA.
LA  - eng
GR  - 2R01DA029121/DA/NIDA NIH HHS/United States
GR  - 1R01DA049737/DA/NIDA NIH HHS/United States
GR  - 1R01NS117906/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20211026
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC8622070
OTO - NOTNLM
OT  - biological barriers
OT  - dysfunction
OT  - endothelial
OT  - stroke
OT  - therapeutic targets
OT  - tight junctions
OT  - viability
COIS- The authors declare no conflict of interest.
EDAT- 2021/11/28 06:00
MHDA- 2021/11/28 06:01
PMCR- 2021/10/26
CRDT- 2021/11/27 01:24
PHST- 2021/09/23 00:00 [received]
PHST- 2021/10/15 00:00 [revised]
PHST- 2021/10/20 00:00 [accepted]
PHST- 2021/11/27 01:24 [entrez]
PHST- 2021/11/28 06:00 [pubmed]
PHST- 2021/11/28 06:01 [medline]
PHST- 2021/10/26 00:00 [pmc-release]
AID - pharmaceutics13111779 [pii]
AID - pharmaceutics-13-01779 [pii]
AID - 10.3390/pharmaceutics13111779 [doi]
PST - epublish
SO  - Pharmaceutics. 2021 Oct 26;13(11):1779. doi: 10.3390/pharmaceutics13111779.