Leaky Brain Syndrome

Today we are discussing a newly acknowledged term, Leaky Brain Syndrome.  In previous broadcasts we have discussed Leaky Gut Syndrome at length and the potential negative health effects of this condition, ranging from autoimmune disease, diabetes, and obesity.  Recently, researchers have provided us with information on how the blood brain barrier (BBB) can also break down, with the result being excessive inflammation in the brain.  This issue is now being tied to worsening of conditions such as Parkinson’s Disease and abnormal thyroid hormone levels in the brain.

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1.Synthesis and Anti-neuroinflammatory Activity of Lactone Benzoyl Hydrazine and 2-nitro-1-phenyl-1H-Indole Derivatives as p38? MAPK Inhibitors.
Cheng B, Lin Y, Kuang M, Fang S, Gu Q, Xu J, Wang L.
Chem Biol Drug Des. 2015 May 9. doi: 10.1111/cbdd.12581. [Epub ahead of print]
PMID: 25960125 [PubMed – as supplied by publisher]
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2.Mitochondrial Crisis in Cerebrovascular Endothelial Cells Opens the Blood-Brain Barrier.
Doll DN, Hu H, Sun J, Lewis SE, Simpkins JW, Ren X.
Stroke. 2015 Apr 28. pii: STROKEAHA.115.009099. [Epub ahead of print]
PMID: 25922503 [PubMed – as supplied by publisher]
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3.Activation of AMPK improves lipopolysaccharide-induced dysfunction of the blood-brain barrier in mice.
Yu HY, Cai YB, Liu Z.
Brain Inj. 2015 Mar 20:1-8. [Epub ahead of print]
PMID: 25794165 [PubMed – as supplied by publisher]
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4.Immune challenge by intraperitoneal administration of lipopolysaccharide directs gene expression in distinct blood-brain barrier cells toward enhanced prostaglandin E<sub>2</sub> signaling.
Vasilache AM, Qian H, Blomqvist A.
Brain Behav Immun. 2015 Feb 9. pii: S0889-1591(15)00021-5. doi: 10.1016/j.bbi.2015.02.003. [Epub ahead of print]
PMID: 25678162 [PubMed – as supplied by publisher]
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5.Parallel regulation of thyroid hormone transporters OATP1c1 and MCT8 during and after endotoxemia at the blood-brain barrier of male rodents.
Wittmann G, Szabon J, Mohácsik P, Nouriel SS, Gereben B, Fekete C, Lechan RM.
Endocrinology. 2015 Apr;156(4):1552-64. doi: 10.1210/en.2014-1830. Epub 2015 Jan 16.
PMID: 25594699 [PubMed – in process]
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6.TNFR1-JNK signaling is the shared pathway of neuroinflammation and neurovascular damage after LPS-sensitized hypoxic-ischemic injury in the immature brain.
Wang LW, Chang YC, Chen SJ, Tseng CH, Tu YF, Liao NS, Huang CC, Ho CJ.
J Neuroinflammation. 2014 Dec 24;11(1):215. doi: 10.1186/s12974-014-0215-2.
PMID: 25540015 [PubMed – in process] Free PMC Article
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7.Overexpression of NMDAR2B in an inflammatory model of Alzheimer’s disease: modulation by NOS inhibitors.
Maher A, El-Sayed NS, Breitinger HG, Gad MZ.
Brain Res Bull. 2014 Oct;109:109-16. doi: 10.1016/j.brainresbull.2014.10.007. Epub 2014 Oct 27.
PMID: 25454121 [PubMed – in process]
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8.Anti-ribosomal P protein autoantibodies from patients with neuropsychiatric lupus impair memory in mice.
Bravo-Zehnder M, Toledo EM, Segovia-Miranda F, Serrano FG, Benito MJ, Metz C, Retamal C, Álvarez A, Massardo L, Inestrosa NC, González A.
Arthritis Rheumatol. 2015 Jan;67(1):204-14. doi: 10.1002/art.38900.
PMID: 25302407 [PubMed – indexed for MEDLINE]
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9.Alpha synuclein is transported into and out of the brain by the blood-brain barrier.
Sui YT, Bullock KM, Erickson MA, Zhang J, Banks WA.
Peptides. 2014 Dec;62:197-202. doi: 10.1016/j.peptides.2014.09.018. Epub 2014 Sep 30.
PMID: 25278492 [PubMed – in process]
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10.Blood-brain barrier dysfunction in mice induced by lipopolysaccharide is attenuated by dapsone.
Zhou T, Zhao L, Zhan R, He Q, Tong Y, Tian X, Wang H, Zhang T, Fu Y, Sun Y, Xu F, Guo X, Fan D, Han H, Chui D.
Biochem Biophys Res Commun. 2014 Oct 24;453(3):419-24. doi: 10.1016/j.bbrc.2014.09.093. Epub 2014 Sep 28.
PMID: 25268765 [PubMed – in process]
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11.Role of the urokinase plasminogen activator system in patients with bacterial meningitis.
Winkler F, Kastenbauer S, Koedel U, Pfister HW.
Neurology. 2002 Nov 12;59(9):1350-5.
PMID: 12427882 [PubMed – indexed for MEDLINE]
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12.Activation of AMPK attenuates lipopolysaccharide-impaired integrity and function of blood-brain barrier in human brain microvascular endothelial cells.
Zhao Z, Hu J, Gao X, Liang H, Liu Z.
Exp Mol Pathol. 2014 Dec;97(3):386-92. doi: 10.1016/j.yexmp.2014.09.006. Epub 2014 Sep 16.
PMID: 25220346 [PubMed – indexed for MEDLINE]
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13.Attenuated Blood-Brain Barrier Dysfunction by XQ-1H Following Ischemic Stroke in Hyperlipidemic Rats.
Fang W, Sha L, Kodithuwakku ND, Wei J, Zhang R, Han D, Mao L, Li Y.
Mol Neurobiol. 2014 Aug 17. [Epub ahead of print]
PMID: 25128027 [PubMed – as supplied by publisher]
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14.Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.
Fenn AM, Skendelas JP, Moussa DN, Muccigrosso MM, Popovich PG, Lifshitz J, Eiferman DS, Godbout JP.
J Neurotrauma. 2015 Jan 15;32(2):127-38. doi: 10.1089/neu.2014.3514. Epub 2014 Nov 13.
PMID: 25070744 [PubMed – in process] Free PMC Article
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15.Salmonella as a biological “Trojan horse” for neoplasia: future possibilities including brain cancer.
Mlynarczyk GS, Berg CA, Withrock IC, Fick ME, Anderson SJ, Laboissonniere LA, Jefferson MA, Brewer MT, Stock ML, Lange JK, Luna KC, Acharya S, Kanuri S, Sharma S, Kondru NC, McCormack GR, Carlson SA.
Med Hypotheses. 2014 Sep;83(3):343-5. doi: 10.1016/j.mehy.2014.06.009. Epub 2014 Jun 16.
PMID: 24986645 [PubMed – in process]
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16.Systemic lipopolysaccharide compromises the blood-labyrinth barrier and increases entry of serum fluorescein into the perilymph.
Hirose K, Hartsock JJ, Johnson S, Santi P, Salt AN.
J Assoc Res Otolaryngol. 2014 Oct;15(5):707-19. doi: 10.1007/s10162-014-0476-6. Epub 2014 Jun 21.
PMID: 24952083 [PubMed – in process]
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17.Somatostatin ameliorates lipopolysaccharide-induced tight junction damage via the ERK-MAPK pathway in Caco2 cells.
Lei S, Cheng T, Guo Y, Li C, Zhang W, Zhi F.
Eur J Cell Biol. 2014 Jul;93(7):299-307. doi: 10.1016/j.ejcb.2014.05.003. Epub 2014 Jun 2.
PMID: 24950815 [PubMed – indexed for MEDLINE]
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18.Systemic injection of low-dose lipopolysaccharide fails to break down the blood-brain barrier or activate the TLR4-MyD88 pathway in neonatal rat brain.
Wang P, You SW, Yang YJ, Wei XY, Wang YZ, Wang X, Hao DJ, Kuang F, Shang LX.
Int J Mol Sci. 2014 Jun 5;15(6):10101-15. doi: 10.3390/ijms150610101.
PMID: 24905408 [PubMed – indexed for MEDLINE] Free PMC Article
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19.Assessment of blood-brain barrier function and the neuroinflammatory response in the rat brain by using cerebral open flow microperfusion (cOFM).
Ghosh A, Birngruber T, Sattler W, Kroath T, Ratzer M, Sinner F, Pieber TR.
PLoS One. 2014 May 22;9(5):e98143. doi: 10.1371/journal.pone.0098143. eCollection 2014.
PMID: 24852285 [PubMed – indexed for MEDLINE] Free PMC Article
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20.Calorie restriction attenuates lipopolysaccharide (LPS)-induced microglial activation in discrete regions of the hypothalamus and the subfornical organ.
Radler ME, Hale MW, Kent S.
Brain Behav Immun. 2014 May;38:13-24. doi: 10.1016/j.bbi.2013.11.014. Epub 2013 Dec 1.
PMID: 24291211 [PubMed – indexed for MEDLINE]
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21.Effects of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide on blood-brain barrier and dopaminergic neurons of rats with lipopolysaccharide-induced Parkinson’s disease.
Wu XL, Wang P, Liu YH, Xue YX.
J Mol Neurosci. 2014 May;53(1):1-9. doi: 10.1007/s12031-013-0175-5. Epub 2013 Nov 20.
PMID: 24254220 [PubMed – indexed for MEDLINE]
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22.Peripheral immunomodulation with ginsenoside Rg1 ameliorates neuroinflammation-induced behavioral deficits in rats.
Zheng X, Liang Y, Kang A, Ma SJ, Xing L, Zhou YY, Dai C, Xie H, Xie L, Wang GJ, Hao HP.
Neuroscience. 2014 Jan 3;256:210-22. doi: 10.1016/j.neuroscience.2013.10.023. Epub 2013 Oct 23.
PMID: 24161284 [PubMed – indexed for MEDLINE]
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23.Selective activation of cannabinoid receptor 2 in leukocytes suppresses their engagement of the brain endothelium and protects the blood-brain barrier.
Rom S, Zuluaga-Ramirez V, Dykstra H, Reichenbach NL, Pacher P, Persidsky Y.
Am J Pathol. 2013 Nov;183(5):1548-58. doi: 10.1016/j.ajpath.2013.07.033. Epub 2013 Sep 18.
PMID: 24055259 [PubMed – indexed for MEDLINE] Free PMC Article
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24.Lipopolysaccharide precipitates hepatic encephalopathy and increases blood-brain barrier permeability in mice with acute liver failure.
Chastre A, Bélanger M, Nguyen BN, Butterworth RF.
Liver Int. 2014 Mar;34(3):353-61. doi: 10.1111/liv.12252. Epub 2013 Aug 2.
PMID: 23910048 [PubMed – in process]
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25.Gut microbiota controls adipose tissue expansion, gut barrier and glucose metabolism: novel insights into molecular targets and interventions using prebiotics.
Geurts L, Neyrinck AM, Delzenne NM, Knauf C, Cani PD.
Benef Microbes. 2014 Mar;5(1):3-17. doi: 10.3920/BM2012.0065. Review.
PMID: 23886976 [PubMed – indexed for MEDLINE]
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26.Modulation of the metabiome by rifaximin in patients with cirrhosis and minimal hepatic encephalopathy.
Bajaj JS, Heuman DM, Sanyal AJ, Hylemon PB, Sterling RK, Stravitz RT, Fuchs M, Ridlon JM, Daita K, Monteith P, Noble NA, White MB, Fisher A, Sikaroodi M, Rangwala H, Gillevet PM.
PLoS One. 2013;8(4):e60042. doi: 10.1371/journal.pone.0060042. Epub 2013 Apr 2.
PMID: 23565181 [PubMed – indexed for MEDLINE] Free PMC Article
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27.Juglone prevents metabolic endotoxemia-induced hepatitis and neuroinflammation via suppressing TLR4/NF-?B signaling pathway in high-fat diet rats.
Peng X, Nie Y, Wu J, Huang Q, Cheng Y.
Biochem Biophys Res Commun. 2015 May 8. pii: S0006-291X(15)00844-X. doi: 10.1016/j.bbrc.2015.04.124. [Epub ahead of print]
PMID: 25964086 [PubMed – as supplied by publisher]
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28.Regulation of Obesity-Related Insulin Resistance with Gut Anti-inflammatory Agents.
Luck H, Tsai S, Chung J, Clemente-Casares X, Ghazarian M, Revelo XS, Lei H, Luk CT, Shi SY, Surendra A, Copeland JK, Ahn J, Prescott D, Rasmussen BA, Chng MH, Engleman EG, Girardin SE, Lam TK, Croitoru K, Dunn S, Philpott DJ, Guttman DS, Woo M, Winer S, Winer DA.
Cell Metab. 2015 Apr 7;21(4):527-42. doi: 10.1016/j.cmet.2015.03.001.
PMID: 25863246 [PubMed – in process]
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29.Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer.
Reunanen J, Kainulainen V, Huuskonen L, Ottman N, Belzer C, Huhtinen H, de Vos WM, Satokari R.
Appl Environ Microbiol. 2015 Jun 1;81(11):3655-62. doi: 10.1128/AEM.04050-14. Epub 2015 Mar 20.
PMID: 25795669 [PubMed – in process]
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30.Gut microbiota as a key player in triggering obesity, systemic inflammation and insulin resistance.
Escobedo G, López-Ortiz E, Torres-Castro I.
Rev Invest Clin. 2014 Sep-Oct;66(5):450-9.
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