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ati
o
n
a
l
Jo
urn
a
l
o
f
P
u
b
lic Hea
l
th Science (IJ
P
HS)
V
o
l.4
,
No
.3
, Sep
t
em
b
e
r
20
15, pp
. 201
~204
I
S
SN
: 225
2-8
8
0
6
2
01
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urn
a
l
h
o
me
pa
ge
: h
ttp
://iaesjo
u
r
na
l.com/
o
n
lin
e/ind
e
x.ph
p
/
IJPHS
Vascular Endothelial Growth Fact
or Concentrati
o
n in Brai
n of
Rat Treated with Anaerobic Exercises
Ro
stika
Fl
o
r
a, Muha
mmad
Z
u
lka
r
na
in, Yulia
na
F
acul
t
y
of
M
e
di
cine
, Univ
er
sitas
Sriwija
ya
,
Indo
nesia
Article Info
A
B
STRAC
T
Article histo
r
y:
Received
J
u
l 24, 2015
Rev
i
sed
Au
g
20
, 20
15
Accepted Aug 30, 2015
Anaerobic
ex
e
r
cis
e
is
a high-
intens
it
y
exer
cis
e
tha
t
ne
eds
qu
ick en
erg
y
supplies obta
i
ne
d in a v
e
r
y
shor
t tim
e.
However
,
this
exerc
i
se m
a
y result
in
tis
s
u
e h
y
pox
ia
which is
ch
arac
teri
zed b
y
the in
cre
a
s
e
of HIF
-
1
α
concen
trat
ion.
T
h
e pres
en
ce of
HIF
-
1
α
will ind
u
ce th
e se
cret
io
n of VEGF
and, even
tua
l
l
y
,
trigger ang
i
ogen
e
sis. Neverth
e
les
s
, it is still uncl
e
ar whether
anaerob
ic
exer
c
i
se will
also
ca
use h
y
pox
ia
in
which th
is co
ndition wi
ll
incre
a
se th
e con
centr
ation
of V
E
GF in
brain
tis
sues. The
aim
o
f
this stu
d
y
was
to find ou
t
the
effe
ct of
a
n
aerobi
c ex
erc
i
s
e
frequ
enc
y
towards
VEGF
concen
trat
ion of
W
i
s
t
ar ra
t bra
i
n
tis
s
u
es
. Br
ain
tissues were taken from rats
trea
ted with
ana
e
robic
exer
cis
e
us
ing treadm
i
l
l
.
This
exer
cis
e
w
a
s
given i
n
differen
t
frequ
e
n
cies
; on
e t
i
m
e
,
three
tim
es
,
an
d s
e
ven tim
es
a
week.
The
data
col
l
e
c
ted
were an
al
yz
ed
us
ing i
ndep
e
ndent t-test. Th
e results of this
s
t
ud
y
s
howed th
at an
aerobi
c ex
ercis
e
don
e once
a week could s
i
gnific
a
n
t
l
y
incre
a
s
e
VEGF
concen
trat
ion (p
< 0.05)
if com
p
ared with
the on
e in con
t
ro
l
group (95.21 ±
31.99 v.s. 63
.36 ±
11.01 pg
/mL). Meanwhile, VEGF
concen
tration of treatmen
t groups given exercis
e
three times a week (47.97 ±
10.68 pg/mL) and seven times
a week
(40
.
56
± 13.98 pg/mL) showed a
significant decr
ease if compared
with
that of control group (63.36 ± 11.01
pg/m
L
). Anaero
b
ic exerc
i
s
e
aff
ect
ed VEGF
concentr
ation as
an indic
a
tor of
angiogen
e
sis in
brain
tissue of
wistar r
a
ts.
Keyword:
Anae
robic
An
gio
g
e
n
esis
Brain tissue
s
Ph
ysical activ
ities
Vascu
l
ar en
dho
th
elial
Copyright ©
201
5 Institut
e
o
f
Ad
vanced
Engin
eer
ing and S
c
i
e
nce.
All rights re
se
rve
d
.
Co
rresp
ond
i
ng
Autho
r
:
Ro
stik
a Fl
o
r
a,
Depa
rt
m
e
nt
of
B
i
om
edi
cal
Sci
e
nce, Fac
u
l
t
y
of
M
e
di
ci
ne,
Uni
v
ersitas Sri
w
ijaya,
Pal
e
m
b
ang
,
S
o
ut
h
o
f
S
u
m
a
t
e
r
a
, I
n
do
nesi
a.
Em
a
il: ro
stik
aflo
ra@un
s
ri.ac.i
d
1.
INTRODUCTION
Anae
robic
physical exercise i
s
a
h
i
gh
-in
t
en
sity activ
ity acq
u
i
ring
imm
e
d
i
ate en
erg
y
in a v
e
ry short
t
i
m
e
, but
i
t
cannot
be d
o
n
e co
nt
i
n
u
o
u
sl
y
[1]
.
Anae
robic environm
ent will
tr
igge
r the accum
u
lation of HIF-1
α
i
n
t
i
ssues.
Wh
en hy
po
xi
a oc
curs
, H
I
F
-
1
α
will tran
slo
cat
e to
cell n
u
c
lei to
m
a
k
e
d
i
m
e
risatio
n
with
HIF-1
β
to
fo
rm
HIF-
1
[
2
]
.
T
h
r
o
ug
h a
c
t
i
v
at
i
on
of
H
I
F-
1,
t
h
e e
x
pr
essi
on
a
num
ber
o
f
gene
s,
i
n
cl
u
d
i
n
g
Va
scul
ar
End
o
t
h
e
lial Gro
w
t
h
Factor (VEGF), will b
e
in
creased
in
o
r
d
e
r to
lessen cell d
e
p
e
n
d
e
nce to
o
x
y
g
e
n
an
d
to
elevate oxyge
n
supply t
o
tissues as
well.
VEGF is an
essen
tial regu
lato
r in
d
e
v
e
lop
i
ng
n
e
w b
l
oo
d
cap
p
illaries (ang
iog
e
n
e
sis) [3
].
The
d
e
v
e
l
o
p
m
en
t of th
ese n
e
w
cap
p
illaries app
e
ars as
a respon
se t
o
m
eet o
x
y
g
e
n
d
e
m
a
n
d
s
in
h
ypox
ic
m
u
scle
t
i
ssues.
Ot
he
r
st
udi
es c
o
nd
uct
e
d
b
o
t
h
i
n
vivo
and
i
n
vitro
ha
d
pr
ov
ed t
h
at
VE
GF
was i
n
v
o
l
v
e
d
i
n
t
h
e
reg
u
l
a
t
i
o
n
o
f
a
ngi
oge
nesi
s
p
r
ocess
[
4
]
.
A st
udy
o
f
Fl
ora
et a
l
indicated t
h
at the
r
e
was
an inc
r
ease
in
VEGF
co
n
c
en
tration
of ca
rdiac m
u
scle tissues
of rats treated
with anaerobic phy
sical exe
r
c
i
ses. The i
n
cre
a
se of
VEGF c
o
ncent
r
ation in a
n
ae
robic
groups
wa
s hi
ghe
r t
h
a
n
t
h
at
o
f
ae
ro
bi
c
one
s [
5
]
.
B
e
si
des car
di
a
c
m
u
scl
e
s, b
r
a
i
n i
s
o
n
e
of t
h
e vi
t
a
l
or
ga
ns
whi
c
h al
so
w
o
rks
ha
rd t
o
m
a
i
n
t
a
i
n
b
o
d
y
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
SN
:
2
252
-88
06
I
J
PH
S Vo
l. 4
,
N
o
. 3
,
Sep
t
emb
e
r
201
5
:
2
01
–
20
4
20
2
bal
a
nce
w
h
en
phy
si
cal
exe
r
c
i
ses occ
u
r.
Ot
her
p
r
evi
ous
r
e
l
a
t
e
d st
udy
st
at
ed t
h
at
an
gi
oge
nesi
s occ
u
r
r
ed
i
n
brai
n m
o
tor cortex tissue
of rats that
were
g
i
ven ae
ro
bi
c
p
h
y
s
i
cal
exerci
s
e
[6]
.
As
pre
v
i
ousl
y
m
e
nt
i
o
n
e
d, i
t
i
s
said
th
at an
aerob
i
c ph
ysical ex
ercise can
cau
se an
g
i
og
en
esis in brain tissu
es,
bu
t th
is statem
en
t
is still
d
e
b
a
tab
l
e [7
]. In
ad
d
ition
,
t
h
e n
u
m
b
e
r
o
f
st
u
d
i
es
reg
a
rd
ing
th
e effect of
an
aerob
ic ph
ysical ex
ercises to
ward
s
an
g
i
o
g
e
n
e
sis i
s
still s
m
all. I
n
no
rm
al b
r
ain tissu
e, it
is sti
ll u
n
e
xp
lain
ed w
h
ether or not an
aerob
ic physica
l
activ
ities co
u
l
d also
in
crease t
h
e secreti
o
n
o
f
VEGF co
n
s
i
d
ering
th
e
fact th
at brain
is a
vital o
r
g
a
n
th
at
relies
o
n
o
x
y
g
e
n su
pp
ly in
ord
e
r t
o
m
a
in
tain
its fu
n
c
tion
.
Th
eref
or
e, it is n
eed
ed to do a
f
u
rth
e
r
stud
y to f
i
n
d
o
u
t
the effect of a
n
aerobic physical ex
erci
se t
o
war
d
s
VE
GF
conce
n
t
r
at
i
o
n
as an i
n
di
cat
o
r
o
f
a
ngi
oge
ne
si
s i
n
W
i
star
rat brai
n tissue
.
2.
R
E
SEARC
H M
ETHOD
Thi
s
was e
xpe
r
i
m
e
nt
al
st
udy
usi
n
g p
o
st
t
e
st
onl
y
co
nt
r
o
l
gr
ou
p de
si
g
n
. Th
i
s
st
udy
was con
d
u
ct
ed i
n
ani
mal
ho
use
of Fac
u
l
t
y
of
M
e
di
ci
ne, U
n
i
v
ersi
t
a
s Pa
dja
j
aran i
n
Feb
r
ua
ry
20
1
5
. T
h
e s
a
m
p
l
e
of t
h
i
s
s
t
udy
was
t
w
ent
y
ei
ght
W
i
st
ar rat
s
ag
ed fr
om
6-8
w
eeks an
d t
a
ke
n
usi
n
g ra
nd
om
sam
p
l
i
ng. T
h
e sam
p
l
e
was devi
ded
in
to
f
o
u
r
gro
ups n
a
m
e
ly P1
, P2
,
P3, an
d P4
.
P1
w
a
s con
t
ro
l gr
oup
an
d P2
, P3, an
d P4
w
e
r
e
tr
eatm
e
n
t
g
r
o
u
p
s
.
Th
e treatm
e
n
t
g
r
ou
p
s
were then
g
i
v
e
n
an
aero
b
i
c ph
ysical activ
ities o
n
a t
r
ead
m
ill
wh
ich was set fo
r twen
ty
m
i
nut
es i
n
spe
e
d
of
3
5
m
/
m
i
nut
e.
T
h
e e
x
er
ci
se was
gi
ven
i
n
di
ffe
rent
f
r
e
que
nci
e
s;
1 t
i
m
e
t
r
eatm
e
nt
(
P
2)
,
3
tim
e
s a week (P3), and
7 times a week
(P4).
Th
e r
e
sear
ch
pr
ocedu
r
e
for
an
aer
o
b
i
c physical ex
er
cises w
a
s
base
d o
n
a m
e
tho
d
devel
ope
d
by
Fah
r
eni
a
a
n
d Fl
o
r
a
et al
[8],
[
5
].
Before the treat
m
e
n
t
s were im
p
l
e
m
en
ted
,
all
expe
ri
m
e
nt
al
ani
m
al
s were a
c
c
l
i
m
a
ti
zed fo
r
one
wee
k
by
p
u
t
t
i
ng t
h
em
on
a l
o
w
-
s
p
eed
t
r
e
a
dm
il
l
.
3.
R
E
SU
LTS AN
D ANA
LY
SIS
There
was a si
gni
fi
cant
di
f
f
er
ence i
n
VE
GF
conce
n
t
r
at
i
o
n
of
brai
n t
i
ssue
s
am
ong g
r
ou
ps
of o
n
e-t
i
m
e
treatm
e
nt (p = 0.044), three-
times a week (p
= 0.034), an
d s
e
ven
-
t
i
m
e
s a
week
(p =
0.
01
1) i
f
c
o
m
p
ared
wi
t
h
th
at of
co
n
t
r
o
l
gr
oup
(Tab
le 1)
. Th
ese f
i
nd
ing
s
i
n
d
i
cate
d
that
anae
robic physical e
x
ercise wit
h
differe
n
t
fre
que
nci
e
s ha
d
a si
g
n
i
f
i
cant
effect
t
o
V
E
G
F
co
nce
n
t
r
at
i
o
n of
W
i
st
ar
rat
brai
n
t
i
ssues
.
Table
1. T
h
e
E
ffect
of Anaerobic Physical E
x
ercise
t
o
wards VEGF Con
c
en
tration
o
f
Wistar Rat Brain
Tissues
Groups
Mean ±
SD
(
pg/m
l
)
P
Contr
o
l
63.
36 ± 11.
01
One-ti
m
e
tre
a
t
m
en
t
95.
21 ± 31.
99
0.
044
Three ti
m
e
s
a we
e
k
47.
97 ± 10.
68
0.
034
Seven day
s
a
week
40.
56 ± 13.
98
0.
011
Table 1 shows that there is an increase
d
VE
GF conce
n
tration
o
f
W
i
star rat b
r
ain
tissu
es in
on
e ti
m
e
t
r
eatm
e
nt
gr
ou
p i
f
com
p
ared
wi
t
h
t
h
at
o
f
c
ont
rol
gr
o
u
p
.
On
t
h
e
ot
he
r
h
a
nd
, t
h
e
co
nce
n
t
r
at
i
o
n
of
VE
GF
was
decrease
d
in treatm
e
nt groups of th
ree tim
e
s
and seve
n times a week. Th
e lowest concentration of
VEGF
w
a
s
f
oun
d in
a
g
r
ou
p g
i
v
e
n sev
e
n –
tim
e tr
eat
men
t
a w
e
ek
.
3.
1.
Discussion
Th
e r
e
su
lts of
th
is stud
y sh
owed
that there
was an increa
sed VEGF
conce
n
tration of
W
i
st
ar rat brain
tissu
es in
on
e-ti
m
e
treat
m
e
n
t
g
r
oup
if co
mp
ared
with
t
h
a
t
of co
nt
rol
g
r
ou
p.
Ho
we
ver
,
t
h
e conce
n
t
r
at
i
on o
f
VEG
F
was
de
creased
i
n
t
r
ea
tm
ent
gr
ou
ps
of
t
h
ree
t
i
m
es an
d se
ve
n t
i
m
es a wee
k
.
Thi
s
c
oul
d
p
o
ssi
bl
y
be
explaine
d t
h
at in one-tim
e a
n
aerobic exe
r
c
i
se there
wa
s
no
b
ody
a
d
a
p
t
a
t
i
on res
p
on
se
t
o
p
h
y
s
i
cal
exerci
se
give
n. T
h
e
body res
p
onds t
h
is physical exercise as
a st
ressor.
The i
n
crease of e
x
ygen
dem
a
nds
during
p
h
y
sical ex
erci
se w
ill lead
t
o
t
i
ssu
e
h
ypo
x
i
a.
Tissu
e
h
ypox
ia w
ill in
h
i
b
it oxyg
en
t
r
an
sfer to
b
r
ai
n
.
B
r
ai
n i
s
very
v
u
l
n
e
r
abl
e
t
o
i
n
suf
f
i
c
i
e
nt
su
pp
l
y
of oxy
ge
n and
gl
uc
ose. I
n
rel
a
xat
i
o
n, o
u
r
brai
n need
s
20
% o
x
y
g
e
n
fr
om
al
l
oxy
gen
dem
a
nds a
n
d
70
% gl
uc
ose.
The i
n
crease
d
dem
a
nd of
oxygen is ac
com
p
ani
e
d
b
y
con
tinu
o
u
s
b
r
ai
n
m
e
tab
o
lic activ
ities. It
n
eeds con
s
ta
n
t
b
l
ood
fl
o
w
to b
r
ai
n
in ord
e
r to
su
pp
ly ad
eq
u
a
te
and
re
gul
a
r
n
u
t
r
i
e
nt
s.
In
o
n
e
m
i
nut
e, b
r
ai
n
need
s 8
0
0
cc
o
f
o
x
y
g
e
n
a
n
d 1
0
0
m
g
of
gl
uc
ose as e
n
e
r
gy
s
o
u
r
ce
s
[9]
.
Th
e
p
r
esen
ce
o
f
h
ypox
ia dur
ing
ph
ysical ex
er
cises can
i
n
cr
ease th
e exp
r
essi
on
of
VEG
F
t
h
ro
ugh
HIF
-
1
α
re
gul
at
i
on.
Th
e el
evat
i
on
of
m
R
NA VEG
F
has s
o
m
e
t
h
i
ng t
o
d
o
wi
t
h
t
h
e
i
n
c
r
ea
se o
f
m
R
NA
HIF
-
1
α
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
PH
S I
S
SN
:
225
2-8
8
0
6
Va
scu
l
a
r
Endoth
e
lia
l G
r
o
w
th
Fa
cto
r
Con
c
entra
tio
n in
Bra
i
n
o
f
Ra
t Trea
ted
with
.... (Ro
s
tika
Flo
r
a
)
20
3
in
d
i
cating
th
at
HIF-1
α
affect
s the expres
sion of VEGF ge
nes [10].
Sim
i
lar studies on e
xpe
rim
e
ntal anim
als
sh
owed
th
at mRNA VEGF o
f
rat m
u
scle
s was in
creased
four ti
m
e
s a
f
ter
sing
le b
out trea
d
m
ill run
. T
h
e
co
n
c
en
tration
was i
n
creased
wh
en
ph
ysical activ
ities were
co
ndu
cted
i
n
hyp
ox
ic env
i
ronmen
t [2
].
Th
e resu
lts of th
is stu
d
y
were in
lin
e
with th
o
s
e
o
f
Flo
r
a
et al
in
wh
ich
th
ere was
an
in
creased
V
E
GF con
c
en
tratio
n
o
f
card
i
ac
m
u
scle tiss
u
es in
on
e-
time an
aero
b
i
c physical ex
ercises [5
]. In
add
itio
n, a
st
udy
of M
a
r
g
ari
t
e
scu o
n
pat
i
ent
s
ex
peri
e
n
c
i
ng
a
c
u
t
e ischemic cereb
ra
l
in
fa
rct
also a
ppeale
d
an i
n
c
r
eased
conce
n
t
r
at
i
o
n of VE
GF (
8
.
2
x 10
3
±
7
.
5 x 1
0
3
) as
a
protective m
echanism
towards
st
r
o
ke hy
poxi
a
[11]. Th
e
conce
n
tration of VE
GF was
also
elevated on
motor c
o
rt
ex
and
striatum
of rats
wh
ich
were treated with
aerob
ic
p
h
y
sical activ
ities [12
]
.
VEG
F
i
s
c
o
ns
i
d
ere
d
as
an
i
m
port
a
nt
an
gi
oge
ni
c
f
actor
in that t
h
e
re
gulation is i
n
c
r
eased afte
r
p
h
y
sical activ
ities an
d
electrical sti
m
u
li ar
e g
i
v
e
n. Th
erefore, th
e in
crease o
f
VEGF p
r
o
v
i
d
e
s i
m
p
o
r
tan
t
sti
m
u
li fo
r angio
g
e
n
e
sis, esp
e
cially in
in
itial
p
h
a
se of trai
nin
g
p
r
og
ram
.
Th
e
VEGF con
cen
t
r
atio
n
of
b
r
ai
n
tissue wa
s inc
r
eased i
n
a treatment group of
one
-tim
e anaerobic
physical
exercise [12],[13].
VEG
F
se
rves
as an i
m
port
a
nt
re
gul
at
o
r
i
n
an
gi
oge
nesi
s [1
4]
.
A
n
gio
g
ene
s
is itself refe
rs to t
h
e
d
e
v
e
l
o
p
m
en
t o
f
n
e
w b
l
o
od cap
p
illaries in
resp
ond
ing
m
u
scle ad
ap
tatio
n
to
lo
wer lev
e
l o
f
ox
yg
en
.
A
n
g
i
og
en
esis
o
ccurs
wh
en th
ere is an im
b
a
lan
ce b
e
t
w
een
tissu
e m
e
tab
o
lic d
e
m
a
n
d
s
an
d th
e ab
ility o
f
b
l
ood
vessel
pe
rf
ussi
on
.
Th
e regu
latio
n
of
VEGF
g
e
n
e
s seem
s to
h
a
v
e
so
m
e
th
in
g
to
do
with
exercise in
ten
s
ity, and
i
t
s
conce
n
t
r
at
i
o
n i
s
i
n
crease
d
s
i
gni
fi
ca
nt
l
y
i
n
hy
p
oxi
c c
o
ndi
t
i
on
[
2
]
.
In t
r
eat
m
e
nt
gr
o
ups
o
f
t
h
r
ee t
i
m
e
s and
seve
n t
i
m
e
s a wee
k
t
h
e c
o
ncent
r
at
i
o
n
o
f
VE
GF
was
decrease
d
si
gnificantly (p <
0.05)
if
co
m
p
ared
with
co
n
t
ro
l group
. Th
e
resu
lt of th
is stu
d
y
was in
lin
e wit
h
Salceda
et al
t
h
at
i
n
ac
ut
e hy
po
xi
a t
h
e e
x
pr
essi
on
o
f
m
R
NA H
I
F
-
1
α
was
increase
d
,
but in re
peated
hy
poxia
t
h
e ex
pressi
on
of
whi
c
h was
d
ecreased a
g
ai
n
[1
5]
. Thi
s
resu
l
t
was al
so su
p
p
o
r
t
e
d
by
a st
u
d
y
of
Hari
k
et al
. I
n
their study, it was stated that
vasc
u
l
arisation
o
ccurred
45%
in
rat b
r
ain
tissues that e
x
perie
n
ced hy
poxia
for
one
wee
k
.
H
o
weve
r,
t
h
e vas
c
ul
ari
s
at
i
o
n wa
s
n
o
t
occu
red
i
n
repeat
e
d
hy
p
oxi
a [
16]
.
Th
e resu
lts of in
d
e
p
e
nd
en
t
t
-test showe
d
tha
t
there was a s
i
gnifi
ca
nt diffe
r
ence
(p <
0.05) betwee
n
VEGF concent
r
ation of brain tissu
es in anaerobic treatm
e
nt groups
if co
m
p
ared
with
th
at o
f
con
t
ro
l o
n
e
.
Anae
robic tre
a
t
m
e
nt with
different
fre
quenci
es affected t
h
e
VEGF c
o
ncent
r
atio
n of
W
i
star rat
brain
tissues.
4.
CO
NCL
USI
O
N
The
res
u
lts showe
d
t
h
at ana
e
robic
physica
l exer
ci
ses
pe
rf
orm
e
d i
n
di
f
f
ere
n
t
f
r
eq
ue
n
c
i
e
s co
ul
d
i
n
fl
ue
nce VE
G
F
co
nce
n
t
r
at
i
o
n of
W
i
st
ar
rat
brai
n
t
i
ssue
.
ACKNOWLE
DGE
M
ENTS
Thi
s
st
u
d
y
was
fu
nde
d
by
a p
o
st
g
r
ad
uat
e
g
r
ant
fr
om
M
i
ni
st
ry
of Hi
ghe
r
Ed
ucat
i
on
& R
e
search a
n
d
Technol
ogy in fiscal year 2015. T
h
ere
f
o
r
e,
t
h
e resea
r
che
r
wo
ul
d
be
ver
y
gr
ateful for t
h
e gra
n
t so that this
st
udy
c
o
ul
d
be
fi
ni
she
d
i
n
t
i
m
e.
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