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12th International Review of. ACh via M2 inflames BBB. BIPOLAR DISORDER. MC by CGRP PACAP. Nice, 22.May 2012. 3 rd. S1 INS. PACAP. 1 st. . ICA miniG. TGG. ?. HOW the P terygo - P alatine G anglion matters in… BIPOLARITY too G. T reviranus, B erne. Noseda 2010.

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HOW the P terygo - P alatine G anglion matters in… BIPOLARITY too G. T reviranus, B erne


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how the p terygo p alatine g anglion matters in bipolarity too g t reviranus b erne

12thInternational Review of

AChvia M2

inflames BBB

BIPOLAR DISORDER

MC byCGRP PACAP

Nice, 22.May 2012

3rd

S1 INS

PACAP

1st

ICA miniG

TGG

?

HOW theP terygo- P alatineG anglionmattersin… BIPOLARITYtooG.Treviranus, Berne

Noseda 2010

Major part

No CGRP !

1893

Sp5C V1

PPG

Beckers 1991

SSN

roseodor

 brainstem

IN MIG attack

SSN-“TG-CERVICAL-complex”

2nd

May 2009 GM  metaAn

HYSTERIA?W.Fliess & S.Freud

? Retrograde INFL

TNF-a

0,1 mm

TENS CH MIG:

1894

Fasmer

NO ACh

VIPPACAPOUTPUT

STIMULATEPPG &

HEAL Cluster Headache

CR 61%, PR 16%, NR 23%

withinminutes!

OPEN BBB

BLOCKPPG &

 STOP HEADPAIN, C2-C3, asthma,(LBP etc.) NOT allodyniain MIG

1: 1st outputCGRP, PACAP, SP MastCell(CGRP-R+)Lennerz 2008

MC degranulationTheoharides 20052: NO DURA CGRP-receptors NO AXON-REFLEX forTG

«Brainstemdisorder»

SPOT

PPG

Non –B~stem

ARTERIES

TG

FACIAL V1,2 PPG  eye, PPG ? BBB

biposuisseinstituteberne

Hysteria & Headache

MC

1

slide2

The Naso-genital Link to... Mast cells

PNS / CNS Mast Cells 

FEMALE & MCs

1: ablationof PPGs in ratscausespseudopregnancy

2: estrus (E2 max) MC cycle anogenitalerogenicareasof VPL thalami? fromdura

3: Ovulation=dangersignal IR. Polycysticor post-MP ovariesMCs

4: doves:  MC in med. habenula courtshipandparenthood.

5: PNS-nerve ligation MC thalamus

MC in Defense:

++ brainfunction avoidancecleaningbhv

++Allergicpreventive

++AntiMicrobial Peptides

+ «suicidal»extra-cellularfibrin traps againstgerms ? WMHI

BUILD VESSELS (VEGF)

Brain MAST cellsCLOSE TO N~s & Art. 3% MIGRATE

VARIATEspecies, area, eco

ACTIVE SP, NGF ,E2

DEGRAN’ PACAP, CGRP, etc.  GFs (NGF…), serineproteasee, iNOS, cytokines (TNFa), heparin, histamine, tryptase, 5-H.T, etc.

MC in psychiatry:

  • PAIN DISORDER
  • AUTISM?

Theoharides 2011 2012

  • BPAD ?
  • Borderline PD ?

Yin & yangof MC in MS

MALE & MCs

1:animal:intraspecies fights MCs med. habenulaattractedby NGF

2: BLOCKED MCsANX-likebhvrat

biposuisse institute berne

2

Mast cells

slide3

PPG PACAP

Putamen

Only L Globus pallidus larger Kempton 2008

Headache ?

MCA

BP ?ACA-MCA-PCA

Shape!

Hwang (Seoul) no Li+2006Li+

+

-

 Search for ? repetitive BBB openingfactors w/ periarterialneurotrophicortoxiceffect

Mast

Cells?

biposuisseinstituteberne

3

Posterior CA !

Arterialpathologyof BPAD

bpad mc gout retroceeding to the brain
BPAD = MC-«GOUT retroceedingtothebrain»

Bugs: bacteria fungi, (virus)

Lesion

Allergen

Chemicals

Heat, cold

Co-occurrence OR (Arnold 2006)

P(BP|FM+)/P(BP|FM-)=x135

P(UP|FM+)/P(UP|FM-)=x2.7

Most BP,UP  FM

Insula

S1 S2

3rd order

Thalamus

status NT p75

SNS 

virus

Sloan 2007

D6 Chemokine-scavenging Rec.

LymphNODES:NGF

Timidity, LT-defense,

Lymphatic

APC to

Top-

down

2nd order

ascension

MC

DRG

A-b

A-d

PAIN+ = TLR4 x HSp90 (?)

Hutchinson 2009

LEFT axilla

PNS 1st order

Glu =< AMPA

via the lymphatics?

i.perit. MC activator rat  at spinal medulla to C2 for head pain

at L6-L2 for visceral pain

Small Slow C-Fiber

“noceffectors”

Dorsal Horn

4

wikipedia, lymphnotes.com & WebMD Scientific American® PICTORIAL SOURCES

injured pns tnf a in brain

W. Ren {Guangzhou}. Neuropsychopharmacology 2011; 36:979-2

injured PNS  TNFain brain

TNFabyMCs?

dampenedby PPG?

  • Spared-Nerve-Injuryr&m TNAa in inplasma -  in CSF in HIPPOCAMPUS WORKING-MEMORY

TNFareleasedby MCs, gliaandneurons

M2 ACh facilitatecognition

M2 antagonistmethoctramineactivates MCs

M2 k.o. mice : likeTNFaWORKING-MEMORY -  maybe M2-cholinergic outputof PPG dampensinflammatorymastcellactivity.

«fibrofog»

biposuisse institute berne

5

vip pacap

12thInternational Review of

BIPOLAR DISORDER

Nice, 23.May 2012

VIP PACAP

Master of N/Immune cellcrosstalk

  • VIP GABA VAthalamus MC releaseofNGF and repair & recoveryin Parkinson-rats Korkmaz 2010, 2012
  • PACAP-38 >>VIP PLC Dural MC degranulationBaun 2012
  • N~protectiveEAE (MS); auto-reactive Th1/Th17
  • VIP  Microglia colitismice
  • Memory & learning
  • Blushingheat (Kellogg 2010)
  • VIP Serum  in Cluster headache

biposuisse institute berne

6

ppg just vasodilation or shame dissociation pain

Silvan Tomkins

RguiltshameL

gyrusrectus

SHAME w/ BLUSH (PPG) :pervasive, also cognitive BRAKE ofexcess, esp. AGGRESSION with SUBMISSIVE dysplay in „neurotic“ CONSPECIFIC STRUGGLE  ISTDPNEUROSIS chron. defeated/-inginflamed immune systemcholerichierarchy,triggeredby «CLENCH, dont BITE»?

PPG :: just vasodilation OR shame, dissociation, pain,?

Nestor 2012 (Boston)

Tangney (Fairfax)

Habib Davanloo

42%

CPS-likesymptoms

DefineBlumer’s SUBICTAL DYSPHORIA in psychiatry …

31%

Dietrich Blumer

5,6%

8,1%

 age

MDD motherORx4.9

50’s

Adol’s

SIDS 2nd same hit?

AW-InfectPPGBBB

dysmorphicbrainstem /caseinoMOentry +

PPG

Auton. brainstem

biposuisse institute berne

7

Yarnitzki 2003

mcs need pkc gsk3 tmx
MCs need PKC & GSK3β TMX

MC exocytosisstartswithCa2+-store openerI145P3 :: Ca2+ replenishedby SOCE e.g. TRPC3 byLI

PKC bslacksthereins (MARCKS-ED) on I145P3furtherneeded(Gadi 11) – at least IF byIgE-on-FcεRI

  • IP3IMPase-(„on site II“)-inhibitor LI
  • MARCKS  LI, VPA(Watson 98)
  • PKC in Mania, sleep(-), AMPH; GWAS-BP: enz(PKC) – in Depression: pmort, modelPKC

PKC-iso LI, VPA, x iso: a,e CNS !TMX a, bI, h, d, zbIbII (a, d) LI, VLPA, SGA NO conc. change but function(Pandev 02, 08)?g only CNS ! SRI x iso: g,d

  • GSK3β in MC essential 4: cytokineprod, chemoattraction, andsurvival :: GSK3β-inhibitors:LI etc.

„theabilityofthe PFC toregulateemotion, thoughtandactionismarkedlyimpairedbyoveractivityof PKC “ Zarate Manji 2009

biposuisse institute berne

8

questions
Questions …

www.biposuisse.ch

biposuisse@bluewin.ch

biposuisse institute berne