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The neurotrophic action and brain protective effect of cerebrolysin
THIRD
of neutwns from the substantia nigra (SN), which is sometimes observed in Alzheimer's disease (AD), was quantitatively analyzed in 10 cases of presenile AD On sections from the and 19 age-matched controls. upper and lower portions of the SN, the pigmented zone (zona compacta) and the non-pigmented zone (zona reticulata) were delineated. and these zones were partitioned into quarters: medial, mid-medial, midThis approach clarified topolateral and lateral. graphical preference of neuronal depletion in the SN 1) pigmented neurons were more severeof AD. namely; ly affected than non-pigmented neurons, 2)neuronal depletion was more marked in the lower SN c-38%, P
LOSS
INTERNATIONAL
CONFERENCE
ON ALZHEIMER’S
DISEASE
197 cYfam.sIR-~lnEman-m &wmmmmmRRh?FmBdcBe’s P.J.Lucass&, D.F.4, R.Ravidl and nretharlanl33Institute far Erain EZL? w, me NetherlELrxB.2: Ii05 %z n A LmiversIty of mnnsylvania, SdnolofMedicine, &i.l&&ia, whited states of America PA 19104. Pi?mventriallarNllczeus(m)
!meslqx-ao~c(~)~
of~hummh~thalmusdomtlcsaaaLlsin~ing~ ALm's &sease. Earlier work e
that the
SN-aGdWN-nsLuansinth3olcJest~~ps~~
incrreaseitlWP-CT3llSi.Se a&ivatedasa~fmman and nuclaolus size. In cm3sr to sea whether this was indeed the case ths 6Blgi-qRparatW (cn) was used a9 a nmsum far secretary activity. lIhe 9cIv and WN wem stained using an antikdy againat Ho160, a gl~ ofthemsdialGA-cist.ernaa.~infixedandparaffin e&e&3adsectianswere~0fhrainsfxuu8amtrals ~~gng~~df~~ 2p to93~.Inaplitian,hrains shmm-'sDx%%3aeraqmgin~fmSn 40 to 97 Ja5u-s and mtche3 far sex, fixatim and pd5tmtm time studied. In ambi~ticm with a micmmvetma~t,weabtaimdagccdsbLningthat was characteriseic for th9 op, indepsndantly of inczmsewithageinsise~ fJxationtiue.An a-t intensitywas c&eLvedinIleuvnsofthe~andpvNin both the amtrol ard ths Alzhailmr gxulp. l%s a&ivatian with q3 am to s&t earlier in life, framatcut55years,intb3Al7heinwgnxpincMtrast
tothsccmtmlgzwpwhar8itappsamdtostartfzwi atart62yaammwat+.~resultspmvidsa3diticn4l datafo.rtbehyp3thesisthatthaSXandFVNnauunsazw i&zed activated in old age. !7%is might
be an explanation for the stability of these nuclei with age ('~E.Sit or lcse it").
195
Abstract withdrawn.
Bra.intissuevas&tainadfxwltheNethsrlandsBrain Bark
198 THE NEUROTROPHIC ACTION AND BRAIN PROTECTIVE EFFECT OF CEREBROLYSIN”’ S.Shimazu, N.Tachikawa. N. Iwamoto, M.Fujinoto.Habikino Laboratory.Fujimoto l-3-40 Nishiotsuka. Matsubara city, Cerebrolysin is a drug produced by
196 GfiRH ANDCRHEFFECTS ONGH
SECRETION AND ON PITUITARYADRENAL AXIS FUNCTION IN DEMENTIA.
pig
brain
brolysin of
had
in dementia. atostatinergic neurotransmission have been reported In a group of demented inpatients (DEM) the baseline ACTH, cortisol and GH levels end the responses of these hormones to CRH and GHRH have been studied. The data were compared to those obtaained in matched healthy controls (NORM). In 7 DEM patients, baseline ACTH levels are significantly lower and cortisol values ePe significantly higher than those found in NORM. CRH induced ACTH and cortisol peaks (D% in respect to basal values) are significantly blunted in DEM. Baseline OH peaks and secretory areas after GHRH are not different in DEM and NORM. In DEM, the inhibition of acetylcholinesterase by pyridostigmine (PYR) does not affect ACTH and cortisol responses to CRH, but enhances GH response to GHRH, which is larger in DEN then in NORM. An impairment of the reciprocal regulation of ACTH and cortisol secretions occurs in DEM and also impaired is the CRH effect on the pituitary-adrenal axis. In DEM only GH secretion is affected by the enhancement of cholinergic neurotransmission. Possibly, a defect of somatostatiz ergic transmission is implicated in this finding.
effect
in
old
investigated
in
in
sin clear
the
dorsal
it’s
I”
Iale. while
by that
obvious the
of
as
NGF
the
other
hand,
Cerebrolysin
demonstrated This
on
on
of
ICR
action
on
like
cholinergic
explained
reported
by
that of
CNS.
effect
deficiency
it’s
permanent
neurotrophic
know”
vs.
as
saline
group.
active
ischemia
action.
some
other
factor
b-FGF.had
a
(I.V.)
since
against or
of
group
neurotrophie The
On
bilateral
mice,
and
of
factor
influence
interesting.
factors,such as NCF,EGF
one
disease,
treated
recently
that
the
intresting.
action
is
antibody,
suggested
very
strain
growth
damage
NGF
Alzheimer’s
using
was
neurite demonstrated
the
protective
protective
lhe
from
investigated
some
isehemic
outgrowth
neurotrophic
is
to
This
also
that
researchers
Cerebrolysin’s
neurite
different
noted
effect
ischemia
embryo
by
was
We
Cerebroly-
Cerebrolysin
Further
Cerebrolysin
significant
effect
a1..1991). of
chicken But
it be
ischemia.
ischenia.
et
inhibited
Cerebrolysin
occlusion
brain
brain
Cerebrolysin
was
also
brain
arterial of
not but
some of
we to
carotide model
have
action
rat
incubation.
NGF.
nay it
transected
results.
after
ol
action,
may
neurotrophic
hr
inhibited.
recently
Cere-
of
I”
that
Cerebrolysin
of
that
action
cells
was
was
hydrolysis reported
(Paier
action.
12
wllh
NCF
Scince
such
see”
neurotrophic
action
NCF.
ganglia
Cerebrolysin
of
rats
outgrowth
was
in
outgrowth
action.
comparing
outgrowth
action
neurite
neurite
Cerebrolysin
been
postnatal
root
enzymatic
al..1990) and delayed neuronal et al.,1991),and enhanced learn-
et
neurotrophie
demonstrated by
and vitro
S.Komatsu and Diagnostics INC. Osaka 580. Japan.
already
protective
(Akai ischemia(Sugita
after
ing
have
brain
fimbria-fornix
death
S.Fonzi,P.Costelli,G.Murialdo,C.Parodi,F.Torre,P.TOsca,S.Porro, E.Di Paolo. Dept.Endocrinological Metabolic Sci. Univ.Genova.16132 Geneva Neurological Clinic. Univ. Pavia. 27100 Pavia Italy. Decreased brain concentrations of Corticotropin Releasing Hormone (CRH) and of somatostatin, end impairments of cholinergic and som
protein.They
T Ito.
and
protective mechanisms brain
may
of
lesions, be
partly
of neutwns from the substantia nigra (SN), which is sometimes observed in Alzheimer's disease (AD), was quantitatively analyzed in 10 cases of presenile AD On sections from the and 19 age-matched controls. upper and lower portions of the SN, the pigmented zone (zona compacta) and the non-pigmented zone (zona reticulata) were delineated. and these zones were partitioned into quarters: medial, mid-medial, midThis approach clarified topolateral and lateral. graphical preference of neuronal depletion in the SN 1) pigmented neurons were more severeof AD. namely; ly affected than non-pigmented neurons, 2)neuronal depletion was more marked in the lower SN c-38%, P
LOSS
INTERNATIONAL
CONFERENCE
ON ALZHEIMER’S
DISEASE
197 cYfam.sIR-~lnEman-m &wmmmmmRRh?FmBdcBe’s P.J.Lucass&, D.F.4, R.Ravidl and nretharlanl33Institute far Erain EZL? w, me NetherlELrxB.2: Ii05 %z n A LmiversIty of mnnsylvania, SdnolofMedicine, &i.l&&ia, whited states of America PA 19104. Pi?mventriallarNllczeus(m)
!meslqx-ao~c(~)~
of~hummh~thalmusdomtlcsaaaLlsin~ing~ ALm's &sease. Earlier work e
that the
SN-aGdWN-nsLuansinth3olcJest~~ps~~
incrreaseitlWP-CT3llSi.Se a&ivatedasa~fmman and nuclaolus size. In cm3sr to sea whether this was indeed the case ths 6Blgi-qRparatW (cn) was used a9 a nmsum far secretary activity. lIhe 9cIv and WN wem stained using an antikdy againat Ho160, a gl~ ofthemsdialGA-cist.ernaa.~infixedandparaffin e&e&3adsectianswere~0fhrainsfxuu8amtrals ~~gng~~df~~ 2p to93~.Inaplitian,hrains shmm-'sDx%%3aeraqmgin~fmSn 40 to 97 Ja5u-s and mtche3 far sex, fixatim and pd5tmtm time studied. In ambi~ticm with a micmmvetma~t,weabtaimdagccdsbLningthat was characteriseic for th9 op, indepsndantly of inczmsewithageinsise~ fJxationtiue.An a-t intensitywas c&eLvedinIleuvnsofthe~andpvNin both the amtrol ard ths Alzhailmr gxulp. l%s a&ivatian with q3 am to s&t earlier in life, framatcut55years,intb3Al7heinwgnxpincMtrast
tothsccmtmlgzwpwhar8itappsamdtostartfzwi atart62yaammwat+.~resultspmvidsa3diticn4l datafo.rtbehyp3thesisthatthaSXandFVNnauunsazw i&zed activated in old age. !7%is might
be an explanation for the stability of these nuclei with age ('~E.Sit or lcse it").
195
Abstract withdrawn.
Bra.intissuevas&tainadfxwltheNethsrlandsBrain Bark
198 THE NEUROTROPHIC ACTION AND BRAIN PROTECTIVE EFFECT OF CEREBROLYSIN”’ S.Shimazu, N.Tachikawa. N. Iwamoto, M.Fujinoto.Habikino Laboratory.Fujimoto l-3-40 Nishiotsuka. Matsubara city, Cerebrolysin is a drug produced by
196 GfiRH ANDCRHEFFECTS ONGH
SECRETION AND ON PITUITARYADRENAL AXIS FUNCTION IN DEMENTIA.
pig
brain
brolysin of
had
in dementia. atostatinergic neurotransmission have been reported In a group of demented inpatients (DEM) the baseline ACTH, cortisol and GH levels end the responses of these hormones to CRH and GHRH have been studied. The data were compared to those obtaained in matched healthy controls (NORM). In 7 DEM patients, baseline ACTH levels are significantly lower and cortisol values ePe significantly higher than those found in NORM. CRH induced ACTH and cortisol peaks (D% in respect to basal values) are significantly blunted in DEM. Baseline OH peaks and secretory areas after GHRH are not different in DEM and NORM. In DEM, the inhibition of acetylcholinesterase by pyridostigmine (PYR) does not affect ACTH and cortisol responses to CRH, but enhances GH response to GHRH, which is larger in DEN then in NORM. An impairment of the reciprocal regulation of ACTH and cortisol secretions occurs in DEM and also impaired is the CRH effect on the pituitary-adrenal axis. In DEM only GH secretion is affected by the enhancement of cholinergic neurotransmission. Possibly, a defect of somatostatiz ergic transmission is implicated in this finding.
effect
in
old
investigated
in
in
sin clear
the
dorsal
it’s
I”
Iale. while
by that
obvious the
of
as
NGF
the
other
hand,
Cerebrolysin
demonstrated This
on
on
of
ICR
action
on
like
cholinergic
explained
reported
by
that of
CNS.
effect
deficiency
it’s
permanent
neurotrophic
know”
vs.
as
saline
group.
active
ischemia
action.
some
other
factor
b-FGF.had
a
(I.V.)
since
against or
of
group
neurotrophie The
On
bilateral
mice,
and
of
factor
influence
interesting.
factors,such as NCF,EGF
one
disease,
treated
recently
that
the
intresting.
action
is
antibody,
suggested
very
strain
growth
damage
NGF
Alzheimer’s
using
was
neurite demonstrated
the
protective
protective
lhe
from
investigated
some
isehemic
outgrowth
neurotrophic
is
to
This
also
that
researchers
Cerebrolysin’s
neurite
different
noted
effect
ischemia
embryo
by
was
We
Cerebroly-
Cerebrolysin
Further
Cerebrolysin
significant
effect
a1..1991). of
chicken But
it be
ischemia.
ischenia.
et
inhibited
Cerebrolysin
occlusion
brain
brain
Cerebrolysin
was
also
brain
arterial of
not but
some of
we to
carotide model
have
action
rat
incubation.
NGF.
nay it
transected
results.
after
ol
action,
may
neurotrophic
hr
inhibited.
recently
Cere-
of
I”
that
Cerebrolysin
of
that
action
cells
was
was
hydrolysis reported
(Paier
action.
12
wllh
NCF
Scince
such
see”
neurotrophic
action
NCF.
ganglia
Cerebrolysin
of
rats
outgrowth
was
in
outgrowth
action.
comparing
outgrowth
action
neurite
neurite
Cerebrolysin
been
postnatal
root
enzymatic
al..1990) and delayed neuronal et al.,1991),and enhanced learn-
et
neurotrophie
demonstrated by
and vitro
S.Komatsu and Diagnostics INC. Osaka 580. Japan.
already
protective
(Akai ischemia(Sugita
after
ing
have
brain
fimbria-fornix
death
S.Fonzi,P.Costelli,G.Murialdo,C.Parodi,F.Torre,P.TOsca,S.Porro, E.Di Paolo. Dept.Endocrinological Metabolic Sci. Univ.Genova.16132 Geneva Neurological Clinic. Univ. Pavia. 27100 Pavia Italy. Decreased brain concentrations of Corticotropin Releasing Hormone (CRH) and of somatostatin, end impairments of cholinergic and som
protein.They
T Ito.
and
protective mechanisms brain
may
of
lesions, be
partly