Disease ⇒ Blood Brain Barrier Integrity {40000610}

Shared Reference Notes

• [1.1] 
  - Trimethylamine, a metabolite of dietary #Choline, #Betaine, and l-#Carnitine, has been reported to exert detrimental impact on the BBB integrity.
• - sodium #Butyrate administration exhibited an alleviating effect on BBB integrity.
• - #Deoxycholic acid and #Ursodeoxycholic acid, may also modulate BBB integrity.
• - #Propionic acid > promote BBB integrity by mitigating oxidative and proinflammatory pathways.
• - physiologically appropriate doses of the oxidized form of trimethylamine, #TMAO, improved the BBB integrity.
• [1.2] [#Short Chain Fatty Acid] 
  - Some SCFAs such as #Butyrate, #Propionate and #Acetate can cross the BBB probably through the monocarboxylate transport system generating a feedback inhibition on brain uptake.
• [1.3] [#Alzheimer’s disease] 
  - Pericyte degeneration leads to BBB breakdown causing brain accumulation of blood-derived neurotoxic molecules. - Pericyte ischemic injury results in contractile rigor and obstruction of capillary blood flow. - Pericyte-specific genetic defects lead to primary familial brain calcification or Fahr’s disease. - Pericytes degenerate and likely play a role in cerebrovascular dysfunction in complex neurological diseases such as AD
• [1.4] 
  - #Tryptophan can cross the BBB and affect #Serotonin synthesis in CNS
• [1.5] 
  - #Ginger and its bioactive components have been shown to penetrate the blood-brain barrier via passive diffusion, suggesting the positive effects of #Ginger in CNS
• [1.6] 
  - #Glyphosate can potentially expose humans through several routes, including skin contact, inhalation, and ingestion of contaminated food and water - #Glyphosate has the ability to cross the blood-brain barrier (BBB). - #Glyphosate can cause neurotoxic effects in animal models. - #Glyphosate exposure has also been associated with behavioral changes in rodents, such as decreased locomotion, increased anxiety levels, depression-like behavior, and impaired learning and memory processes
• [1.7] 
  - Bacterial EVs have been described with capability to cross the blood-brain barrier
• [1.8] [#Autism] 
  - increased intestinal permeability is common in autistic individuals, potentially explaining increased flux of #4EP and/or #4EPS across the gut epithelium and the Blood Brain Barrier [BBB].
• [1.9] [#Alzheimer’s disease] [#Candida albicans] [#Amyloid-beta] 
  - C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted #Aspartic proteinases (Saps) and #Candidalysin. - Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. - Saps also hydrolyze amyloid precursor protein (APP) into amyloid b (Ab)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while #Candidalysin engages the integrin CD11b (Mac-1) on microglia.
• [#Indole] [#Alcohol Consumption] - Alcohols promote dysbiosis and gut permeability and may alter the mucosal tight junctions and the immune activity in the GI tract, leading to a modification of gut barrier integrity, which allows microbial products such as indoles and FA to cross into the circulatory system
• - #Propanoic acid passes the gut-blood and blood–brain barriers, it could travel from the intestine to the CNS
• [1.11] [#Short Chain Fatty Acid] 
  - SCFAs can cross the BBB and activate (#Propionate) or inhibit microglia in addition to favoring the inflammatory process.
• [1.12] 
  - #Propionic acid binds to GPR41 in brain endothelial cells, hinders low-density lipoprotein receptor-related protein 1(LRP-1) expression through a CD14-dependent mechanism, and shields the blood-brain barrier from #Oxidative stress via NRF2 signaling

References Notes