Transcript PPG

12th
International Review of
BIPOLAR DISORDER
HOW the
P terygoHYSTERIA? P alatine
W.Fliess & S.Freud
G anglion
matters in…
BIPOLARITYtoo
Nice, 22.May 2012
ACh via M2
inflames BBB
MC by CGRP PACAP
PACAP

3rd S1
1st
?
INS
TGG
SPOT
1893
PPG
G. Treviranus, Berne
GM 
metaAn
1894
Beckers 1991
TENS CH
MIG :
Sp5C V1
SSN
SSN-“TGCERVICALcomplex”
2nd
? Retrograde INFL
TNF-a
Fasmer
NO ACh
Non
–
•0,1 mm
B~stem
PPG
rose odor 
 brainstem
IN MIG attack
May 2009
Major part
Noseda 2010
No CGRP !
VIP PACAP
OUTPUT

FACIAL V1,2
PPG
 eye,
PPG ? BBB
STIMULATE PPG &
 HEAL Cluster
Headache
CR 61%, PR 16%, NR 23%
within minutes!
 OPEN BBB
ARTERIES BLOCK PPG &
 STOP HEADPAIN,
C2-C3, asthma, (LBP etc.)
NOT allodynia in MIG
1: 1st output CGRP, PACAP, SP
 Mast Cell (CGRP-R+) Lennerz 2008
MC degranulation Theoharides 2005
2: NO DURA CGRP-receptors
 NO AXON-REFLEX for TG
«Brainstem disorder»
TG
MC Hysteria & Headache
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The Naso-genital Link to ... Mast
PNScells
/ CNS Mast Cells 
FEMALE & MCs
MC in Defense:
Brain MAST cells
1: ablation of PPGs in rats
causes pseudopregnancy
CLOSE TO N~s & Art.
++ brain function 
2: estrus (E2 max) MC
avoidance cleaning bhv
cycle  anogenital
3% MIGRATE
erogenic areas of VPL
VARIATE species, area, eco ++Allergic preventive
thalami ? from dura
3: Ovulation=danger signal
++Anti Microbial Peptides
ACTIVE  SP, NGF ,E2
 IR. Polycystic or postDEGRAN’ PACAP, CGRP, etc. + «suicidal» extra-cellular
MP ovaries  MCs
 GFs (NGF…), serine
fibrin traps against
4: doves:  MC in med.
habenula  courtship and
proteasee, iNOS, cytokines
germs  ? WMHI
parenthood.
5: PNS-nerve ligation
  MC thalamus
(TNFa), heparin, histamine,
tryptase, 5-H.T, etc.
Yin & yang of
MC in MS
MALE & MCs
1:animal:intraspecies
fights  MCs med.
habenula attracted
by NGF
BLOCKED MCs
ANX-like bhv rat
BUILD VESSELS (VEGF)
MC in psychiatry:
 PAIN DISORDER
 AUTISM?
Theoharides 2011 2012
 BPAD ?
 Borderline PD ?
2:
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Mast cells
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PPG PACAP
Putamen
Only L Globus
pallidus larger
Kempton 2008
Headache ?
Shape!
MCA
BP ? ACA-MCA-PCA
Hwang (Seoul)
+
2006 Li
no Li+
+
Mast
Cells
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?
Posterior CA !
 Search for ? repetitive
BBB opening factors w/
periarterial neurotrophic or
toxic effect
Arterial pathology of BPAD
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BPAD = MC-«GOUT retroceeding to the brain»
Co-occurrence OR
Bugs:
(Arnold 2006)
P(BP|FM+)/P(BP|FM-)=x135
P(UP|FM+)/P(UP|FM-)=x2.7
Most BP,UP  FM
bacteria
fungi, (virus)
Lesion
Allergen
Chemicals
Heat, cold
Insula
Thalamus
D6 Chemokinescavenging Rec.
Lymphatic
APC to
A-b
MC
A-d
LEFT
axilla
PNS 1st order
Glu =< AMPA
Small Slow C-Fiber
“noceffectors”


S1 S2
3rd order
status
 NT p75
LymphNODES:NGF
SNS
Timidity, LT-defense,

Topvirus
down
2nd orderSloan 2007
ascension
PAIN+ =
TLR4 x
HSp90 (?)
Hutchinson 2009
via the lymphatics ?
i.perit. MC activator rat  at spinal
medulla to C2 for head pain
 at L6-L2 for visceral pain
wikipedia, lymphnotes.com & WebMD Scientific American® PICTORIAL SOURCES
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W. Ren {Guangzhou}. Neuropsychopharmacology 2011; 36:979-2
injured PNS  TNFa in brain
• Spared-Nerve-Injury r&m TNAa  in in plasma  in CSF in
HIPPOCAMPUS
WORKING-MEMORY 
•TNFa byMCs?
• dampened by
PPG?
TNFa released by MCs, glia and neurons
M2 ACh  facilitate cognition
«fibrofog»
M2 antagonist methoctramine activates MCs
M2 k.o. mice : like TNFa WORKING-MEMORY  -
 maybe M2-cholinergic output of PPG dampens
inflammatory mast cell activity.
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12th
International Review of
BIPOLAR DISORDER
Nice, 23.May 2012
VIP PACAP
Master of N/Immune cell crosstalk 
VIP GABA VAthalamus  MC release of NGF and
 repair & recovery in Parkinson-rats Korkmaz 2010, 2012
PACAP-38 >>VIP PLC Dural MC degranulation Baun 2012
N~protective EAE (MS); auto-reactive Th1/Th17
VIP  Microglia  colitis mice
Memory & learning
Blushing heat (Kellogg 2010)
VIP Serum  in Cluster headache
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PPG :: just vasodilation OR shame, dissociation, pain,?
Silvan Tomkins
SHAME w/ BLUSH (PPG) : pervasive, also R guilt shame L
cognitive BRAKE of excess, esp. AGGRESSION
gyrus rectus
with SUBMISSIVE dysplay in „neurotic“ CONSPECIFIC
Habib Davanloo
STRUGGLE  ISTDP NEUROSIS chron. defeated/-ing Nestor 2012 (Boston)
inflamed immune system  choleric hierarchy,
Tangney (Fairfax)
triggered by «CLENCH, dont BITE»?
42%
CPS-like symptoms
Dietrich
Blumer
Define Blumer’s SUBICTAL
DYSPHORIA in psychiatry …
31%
5,6% 8,1%
 age
MDD
mother
ORx4.9
50’s
SIDS 2nd same hit?
AW-InfectPPGBBB
Adol’s
PPG
dysmorphic brainstem biposuisse institute berne
Yarnitzki 2003
/caseinoMO entry +
Auton. brainstem
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MCs need PKC & GSK3β TMX
MC exocytosis starts with Ca2+-store opener I145P3 ::
Ca2+ replenished by SOCE e.g. TRPC3  by LI
PKC b slacks the reins (MARCKS-ED) on I145P3 further
needed (Gadi 11) – at least IF by IgE-on-FcεRI
„the ability of the PFC to
• IP3  IMPase-(„on site II“)-inhibitor LI regulate emotion, though
and action is markedly
• MARCKS   LI, VPA (Watson 98)
impaired by overactivity o
• PKC  in  Mania, sleep(-), AMPH; GWAS-BP:
PKC “ Zarate Manji 2009
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: cytokine prod, chemoattraction, and
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survival :: GSK3β-inhibitors:
LI etc.
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Questions …
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[email protected]
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