PMID- 30231628
OWN - NLM
STAT- MEDLINE
DCOM- 20191014
LR  - 20191014
IS  - 1440-1614 (Electronic)
IS  - 0004-8674 (Linking)
VI  - 52
IP  - 10
DP  - 2018 Oct
TI  - Leaky brain in neurological and psychiatric disorders: Drivers and consequences.
PG  - 924-948
LID - 10.1177/0004867418796955 [doi]
AB  - BACKGROUND: The blood-brain barrier acts as a highly regulated interface; its 
      dysfunction may exacerbate, and perhaps initiate, neurological and 
      neuropsychiatric disorders. METHODS: In this narrative review, focussing on 
      redox, inflammatory and mitochondrial pathways and their effects on the 
      blood-brain barrier, a model is proposed detailing mechanisms which might explain 
      how increases in blood-brain barrier permeability occur and can be maintained 
      with increasing inflammatory and oxidative and nitrosative stress being the 
      initial drivers. RESULTS: Peripheral inflammation, which is causatively 
      implicated in the pathogenesis of major psychiatric disorders, is associated with 
      elevated peripheral pro-inflammatory cytokines, which in turn cause increased 
      blood-brain barrier permeability. Reactive oxygen species, such as superoxide 
      radicals and hydrogen peroxide, and reactive nitrogen species, such as nitric 
      oxide and peroxynitrite, play essential roles in normal brain capillary 
      endothelial cell functioning; however, chronically elevated oxidative and 
      nitrosative stress can lead to mitochondrial dysfunction and damage to the 
      blood-brain barrier. Activated microglia, redox control of which is mediated by 
      nitric oxide synthases and nicotinamide adenine dinucleotide phosphate (NADPH) 
      oxidases, secrete neurotoxic molecules such as reactive oxygen species, nitric 
      oxide, prostaglandin, cyclooxygenase-2, quinolinic acid, several chemokines 
      (including monocyte chemoattractant protein-1 [MCP-1], C-X-C motif chemokine 
      ligand 1 [CXCL-1] and macrophage inflammatory protein 1alpha [MIP-1alpha]) and the 
      pro-inflammatory cytokines interleukin-6, tumour necrosis factor-alpha and 
      interleukin-1beta, which can exert a detrimental effect on blood-brain barrier 
      integrity and function. Similarly, reactive astrocytes produce neurotoxic 
      molecules such as prostaglandin E2 and pro-inflammatory cytokines, which can 
      cause a 'leaky brain'. CONCLUSION: Chronic inflammatory and oxidative and 
      nitrosative stress is associated with the development of a 'leaky gut'. The 
      following evidence-based approaches, which address the leaky gut and blood-brain 
      barrier dysfunction, are suggested as potential therapeutic interventions for 
      neurological and neuropsychiatric disorders: melatonin, statins, probiotics 
      containing Bifidobacteria and Lactobacilli, N-acetylcysteine, and prebiotics 
      containing fructo-oligosaccharides and galacto-oligosaccharides.
FAU - Morris, Gerwyn
AU  - Morris G
AD  - 1 IMPACT Strategic Research Centre, Deakin University School of Medicine, and 
      Barwon Health, Geelong, VIC, Australia.
FAU - Fernandes, Brisa S
AU  - Fernandes BS
AD  - 1 IMPACT Strategic Research Centre, Deakin University School of Medicine, and 
      Barwon Health, Geelong, VIC, Australia.
AD  - 2 Centre for Addiction and Mental Health (CAMH) and Department of Psychiatry, 
      University of Toronto, Toronto, ON, Canada.
FAU - Puri, Basant K
AU  - Puri BK
AD  - 3 Department of Medicine, Hammersmith Hospital, Imperial College London, London, 
      UK.
FAU - Walker, Adam J
AU  - Walker AJ
AD  - 1 IMPACT Strategic Research Centre, Deakin University School of Medicine, and 
      Barwon Health, Geelong, VIC, Australia.
FAU - Carvalho, Andre F
AU  - Carvalho AF
AD  - 2 Centre for Addiction and Mental Health (CAMH) and Department of Psychiatry, 
      University of Toronto, Toronto, ON, Canada.
FAU - Berk, Michael
AU  - Berk M
AUID- ORCID: 0000-0002-5554-6946
AD  - 1 IMPACT Strategic Research Centre, Deakin University School of Medicine, and 
      Barwon Health, Geelong, VIC, Australia.
AD  - 4 Orygen, The National Centre of Excellence in Youth Mental Health, The 
      Department of Psychiatry and The Florey Institute of Neuroscience and Mental 
      Health, The University of Melbourne, Parkville, VIC, Australia.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Aust N Z J Psychiatry
JT  - The Australian and New Zealand journal of psychiatry
JID - 0111052
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Blood-Brain Barrier/*metabolism
MH  - Humans
MH  - Inflammation/complications/*metabolism
MH  - Mental Disorders/complications/*metabolism
MH  - Nervous System Diseases/complications/*metabolism
MH  - Reactive Nitrogen Species/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - Inflammation
OT  - blood-brain barrier
OT  - depression
OT  - leak brain
OT  - microbiota
EDAT- 2018/09/21 06:00
MHDA- 2019/10/15 06:00
CRDT- 2018/09/21 06:00
PHST- 2018/09/21 06:00 [entrez]
PHST- 2018/09/21 06:00 [pubmed]
PHST- 2019/10/15 06:00 [medline]
AID - 10.1177/0004867418796955 [doi]
PST - ppublish
SO  - Aust N Z J Psychiatry. 2018 Oct;52(10):924-948. doi: 10.1177/0004867418796955.