Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions
The effect of vitamin E on the blood-brain barrier (BBB) permeability was studied under conditions of pentylenetetrazole (PTZ)-induced convulsions in aged (23- to 24-month-old) male albino rats; Evans Blue was used as a tracer. The BBB permeability was found to considerably increase in rats with PTZ...
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Інститут фізіології ім. О.О. Богомольця НАН України
2010
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| Cite this: | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions / H. Yorulmaz, F. Burcu Seker, B. Oztas // Нейрофизиология. — 2010. — Т. 42, № 5. — С. 418-423. — Бібліогр.: 45 назв. — англ. |
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| author | Yorulmaz, H. Burcu Seker, F. Oztas, B. |
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| citation_txt | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions / H. Yorulmaz, F. Burcu Seker, B. Oztas // Нейрофизиология. — 2010. — Т. 42, № 5. — С. 418-423. — Бібліогр.: 45 назв. — англ. |
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| description | The effect of vitamin E on the blood-brain barrier (BBB) permeability was studied under conditions of pentylenetetrazole (PTZ)-induced convulsions in aged (23- to 24-month-old) male albino rats; Evans Blue was used as a tracer. The BBB permeability was found to considerably increase in rats with PTZ-evoked seizures; the Evans Blue contents in the left and right hemispheres and cerebellum + brainstem region were significantly higher than those in the control. Vitamin E used in the dose of 70 mg/kg exerted practically no beneficial effect on the increased BBB permeability in rats with seizures, while a greater dose of vitamin E (700 mg/kg) exerted a significant protective effect, especially with respect to the cerebellum + brainstem regions (P < 0.01). The seizure-related rise in the arterial blood pressure was also smaller in the latter experimental group. Thus, our observations confirm the importance of the dose of vitamin E as a protective factor for the BBB permeability and demonstrate that the dose dependence of this antioxidant in aged animals dif fers from that in younger or ganisms.
На старих (вік 23–24 місяці) самцях білих щурів досліджували вплив вітаміну Е на розлади проникності гематоенцефалічного бар’єра (ГЕБ), пов’язані з розвитком судомної активності, котра була індукована введенням пентилентетразолу (ПТЗ); як трасер використовували барвник Еванс блакитний. У тварин із ПТЗ-викликаними судомами проникність ГЕБ значно збільшувалася; вміст барвника в тканинах лівої та правої мозкових півкуль, мозочка та стовбура мозку вірогідно перевищував відповідні значення в контролі. Вітамін Е в дозі 70 мг/кг практично не справляв позитивного впливу на збільшену проникність ГЕБ у тварин із судомною активністю. Застосування ж вітаміну Е в більших дозах (700 мг/кг) забезпечувало істотний протективний ефект, особливо щодо зразків тканин мозочка та стовбура мозку (P < 0.01). Підвищення артеріального кров’яного тиску, пов’язане з розвитком судом, в останній з експериментальних серій було помірнішим, ніж у двох інших серіях. Отже, наші спостереження підтверджують важливість дозування вітаміну Е як протективного фактора щодо проникності ГЕБ та вказують на те, що залежність від дози цього вітаміну, використовуваного як антиоксидант, у старих тварин істотно відрізняється від такої у молодших організмів.
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НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 5418
UDC 612.82+612.825.3+576.161.3+612.67
H. YORULMAZ,1 F. BURCU SEKER,2 and B. OZTAS3
EFFECT OF VITAMIN E ON THE BLOOD-BRAIN BARRIER PERMEABILITY
IN AGED RATS WITH PTZ-INDUCED CONVULSIONS
Received August 12, 2010.
The effect of vitamin E on the blood-brain barrier (BBB) permeability was studied under
conditions of pentylenetetrazole (PTZ)-induced convulsions in aged (23- to 24-month-old) male
albino rats; Evans Blue was used as a tracer. The BBB permeability was found to considerably
increase in rats with PTZ-evoked seizures; the Evans Blue contents in the left and right
hemispheres and cerebellum + brainstem region were significantly higher than those in the
control. Vitamin E used in the dose of 70 mg/kg exerted practically no beneficial effect on the
increased BBB permeability in rats with seizures, while a greater dose of vitamin E (700 mg/kg)
exerted a significant protective effect, especially with respect to the cerebellum + brainstem
regions (P < 0.01). The seizure-related rise in the arterial blood pressure was also smaller
in the latter experimental group. Thus, our observations confirm the importance of the dose
of vitamin E as a protective factor for the BBB permeability and demonstrate that the dose
dependence of this antioxidant in aged animals differs from that in younger organisms.
Keywords: epilepsy, seizures, blood-brain barrier, permeability, pentylenetetrazole,
vitamin E, geriatric.
1 Halic University School of Health Sciences, Halic University, Istanbul,
Turkey.
2 Faculty of Medicine,Yeditepe University, Istanbul, Turkey.
3 Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Correspondence should be addressed to Hatice Yorulmaz
(e-mail: haticeyorulmaz@halic.edu.tr).
INTRODUCTION
Epilepsy is a disease characterized by recurrent
epileptic seizure attacks induced by significantly
transformed cerebral activity. It was found that the
development of such attacks is related to the appearance
of a great amount of reactive oxygen species (ROSs)
within the brain [1]. The state of epileptic attacks
allows the molecules of polar compounds, proteins,
neurotransmitters, and other agents of large molecular
weights to permeate much easier into the brain
because of demolishing of the blood-brain barrier
(BBB) [2, 3]. Additionally, membrane phospholipids
release arachidonic acid due to increased oxygen
consumption during the attacks [4]. Production of
free radicals increases under such conditions, in
particular, due to metabolization of arachidonic acid
by cyclooxygenase. [5]. Free radicals can play the
role of a powerful effector causing an increment in the
BBB permeability; this can result in the creation of
insults in the cerebral vascular endothelium [6, 7].
Biological effects of free radicals are controlled in
vivo by a number of antioxidants, such as vitamins
E, C, and A and glutathione [8, 9]. Vitamin E is one
of the most important chain-breaking antioxidants; it
provides oxidative phosphorylation to continue (by
preventing accumulation of high-energy phosphates
in the mitochondria) and protects cell membranes
against oxidative insult by regulating production of
free radicals [10, 11].
In our studies, we found that vitamin E exerts a
protective effect on the BBB in the course of epileptiform
attacks created by introduction of pentylenetetrazole
(PTZ) in young and adult rats [12]. However, the effect
of vitamin E on the BBB permeability under conditions
of convulsions constituted in aged organisms is not
clear. In this study, we intended to examine the effect
of vitamin E on the BBB permeability in the case of
PTZ-induced convulsions in aged animals and the dose
dependence of this effect.
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 5 419
EFFECT OF VITAMIN E ON THE BLOOD-BRAIN BARRIER
METHODS
The experimental procedure was in accordance with
the Helsinki Declaration (2004). Forty aged (23- to
24-month-old) Wistar albino rats were used in the
experiments. The animals were divided into four
groups: group 1 (control), group 2 (animals with PTZ-
induced convulsions, PTZ group), and groups 3 and
4 (rats manifesting such PTZ-evoked convulsions and
treated with vitamin E in doses 70 and 700 mg/kg,
groups PTZ + E70 and PTZ + 700, respectively). Each
group consisted of 10 animals.
Cannulations of the femoral artery and vein were
performed in animals under ether anesthesia. The
blood pressure was measured in the above artery. The
BBB permeability was characterized using an Evans
Blue tracer (4 ml/kg, i.v.). Pentylenetetrazole was i.v.
injected in the dose of 100 mg/kg into rats of groups 2
to 4, in order to induce convulsions after Evans Blue
was given. Vitamin E was i.p. injected 30 min before
Evans Blue injection in the above-mentioned doses
(70 and 700 mg/kg) in rats of groups 3 and 4. The
seizure attacks were monitored for 20 min. Generalized
convulsions characterized by tonic/clonic contractions
of the limb and trunk muscles were observed in all
animals.
The brains of the rats were elutriated by perfusion
with 0.9% NaCl solution via the left ventricle 25 min
after Evans Blue injection. Then, the brains were
dissected and separated into the left hemisphere, right
hemisphere, and cerebellum + brainstem regions.
Wet masses of the dissected samples were measured.
Afterwards, each brain region was homogenized
by placing in tubes with phosphate buffer (2.5 ml).
A 60% solution of trichloroacetic acid (2.5 ml) was
put in each tube after homogenizing; this procedure
provided separation of Evans Blue from albumins by
centrifuging with a vortex for 2 min. After the vortex
process, the tubes were kept at 4°C for 30 min and
centrifuged at 1,000g for 30 min. After centrifuging, the
absorbance values were read spectrophotometrically
at a 620 nm wavelength (after decanting supernatants
to spectrophotometer tubes). The Evans Blue content
values (µg/mg tissue) were calculated for brain tissue
samples using the Evans Blue absorbance-quantity
regression equation and catenary via the obtained
absorbance values. The statistical analysis was
performed using ANOVA.
RESULTS
No differences were observed from the aspect of
intensity of the tonic/clonic contraction phase during
the epileptic attacks in groups 2-4 of rats injected
with PTZ. The averaged values of blood pressure in
all animal groups are shown in Fig. 1. As can be seen,
no significant differences of the pre-seizure blood
pressure values in groups 2-4 from those in group 1
(control) were observed. The development of PTZ-
induced convulsions resulted in a significant increase
(by about 42%) in the blood pressure in group 2.
Injection of vitamin E in a smaller dose (group 3)
exerted no effect on the value of this shift. At the same
time, in group 4 (PTZ + E700), a seizure-related rise in
the blood pressure was also significant, as compared
with the control, but noticeably less intense (by about
32%) than that in group 3.
In control animals (group 1), the mean Evans Blue
concentrations in the left and right hemispheres and
in the cerebellum + brainstem regions were found to
be 0.288 ± 0.067, 0.295 ± 0.076, and 0.368 ± 0.078
(M ± s.d.) µg/mg tissue, respectively. The corresponding
values in group 2 after the development of PTZ-induced
seizures were noticeably higher (0.521 ± 0.158, 0.404 ±
± 0.045, and 0.879 ± 0.232 µg/mg tissue, i.e., the
0
40
80
120
160
1 2 3 4
Fig 1. Mean values of the arterial blood pressure (mm Hg) in groups
1-4 of experimental rats. 1) Control group, 2) animal group with
pentylenetetrazole (PTZ)-induced convulsions, 3 and 4) groups of
rats with such seizures treated with vitamin E in doses of 70 (3) and
700 (4) mg/kg. In 2-4, open and filled columns correspond to the
blood pressure values measured before PTZ injections and to those
measured within the seizure period, respectively. Means ± s.d. are
shown. Asterisks show cases of a significant difference from control
(P < 0.05).
Р и с. 1. Середні значення артеріального кров’яного тиску в
групах 1–4 (1-4) експериментальних щурів.
mm Hg
*
*
*
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 5420
H. YORULMAZ, F. BURCU SEKER, and B. OZTAS
increments were 81, 37, and 128 %, respectively
(P < 0.05 or P < 0.01; Fig. 2). These shifts were indicative
of a significant increase in the BBB permeability in
the course of PTZ-induced convulsions.
When aged rats with PTZ-induced seizure activity
were treated with vitamin E in the smaller dose used
(70 mg/kg; PTZ + E70 group), the mean Evans Blue
concentrations in the above-mentioned cerebral
regions were the following: 0.618 ± 0.159 and 0.611 ±
± 0.171 µg/mg tissue in the left and right hemisphere
and 0.713 ± 0.183 µg/mg in the cerebellum + brainstem
(Fig. 2). Thus, vitamin E applied in the above dose
exerted practically no beneficial effect on the increased
BBB permeability. The Evans Blue contents in the
hemispheres were even somewhat greater than those
in group 2. The content of the dye in the cerebellum +
+ brainstem was mildly (by 18 %) smaller than the
respective value in group 2, but the difference was
insignificant (P > 0.05).
In group 4 (rats with PTZ-induced convulsion
activity treated with vitamin E in the greater dose,
700 mg/kg), the amount of Evans Blue in the left
hemisphere was insignificantly smaller (P > 0.05)
than that in group 2 (PTZ), and this index in the right
hemisphere was nearly the same as that in the latter
group (with no vitamin E). At the same time, the mean
concentration of the dye in the cerebellum + brainstem
of group-4 rats (0.511 ± 0.105 µg/mg) was 37 % lower
(P < 0.01) than the respective value in group 2
(Fig. 2).
Greater values of standard deviations of the Evans
Blue contents in brain tissues of animals of groups
2-4, as compared with the corresponding figures in
the control group 1, should be, probably, especially
mentioned. In other words, the individual variability
of the state of the BBB in animals with PTZ-induced
seizures (both treated and not treated with vitamin E)
was rather extensive.
DISCUSSION
Our experiments demonstrated that: i) vitamin E is
capable, in principle, of exerting a protective effect on
the disturbed BBB permeability in old animals with
experimentally induced epileptiform seizure activity,
and ii) the respective effects in aged rats differ
significantly from those in younger animals.
The BBB permeability was shown to considerably
increase during epileptic seizure attacks [2, 13]. As was
suggested, increased production of ROSs represents
one of the crucial factors providing greater BBB
permeability values during an after such attacks [12,
14]. A protective effect of vitamin E, which is well-
known as an important antioxidant agent, in particular
with respect to endothelial cells, was demonstrated in
a few studies [12, 15].
A significant increment in the arachidonic acid
concentration together with that for free fatty acids
was observed in experiments with PTZ-induced seizure
attacks [4]. Metabolization of arachidonic acid with
the involvement of cyclooxygenase and lipooxigenase
causes intensified free radical generation [5]. Free
radicals primarily start lipid peroxidation by reacting
with unsaturated fatty acids in cell and organelle
membranes [8]. Lipid peroxidation in the cerebral
endothelial cell membranes is, probably, one of the
main reasons for an increment in the BBB permeability
[6, 7]. The antioxidants, such as vitamins A, C, and
(especially) E were shown to exert a protective effect
on the BBB during epileptic attacks [12, 15, 17].
Vitamin E inactivates lipid peroxyl, superoxides, and
other reactive species [10, 18]. The most important
cellular function of vitamin E is to protect cell
membranes by inhibiting peroxidation of unsaturated
fatty acids [19].
0
0.2
0.4
0.6
0.8
1.0
1.2
1 2 3 4 1 2 3 4 1 2 3 4
µg/mg tissue
А B C
Fig. 2. Contents of the tracer (Evans Blue, µg/mg tissue) in samples
of the left brain hemisphere, right hemisphere, and cerebellum +
+ brainstem regions (A-C, respectively) in groups 1-4 of experimental
rats. Intragroup means ± s.d. are shown. Designations of animal
groups are the same as in Fig. 1. One and two asterisks show cases
of significant differences (P < 0.05 and P < 0.01, respectively)
from the control group 1; two crosses show a significant difference
(P < 0.01) from the value in group 2 (PTZ).
Р и с. 2. Вміст трасера (Еванса блакитного, мкг/мг тканини) у
зразках лівої та правої мозкових півкуль та ділянки мозочка й
стовбура мозку (А–C відповідно) у групах експериментальних
тварин 1–4 (1-4).
*
* *
*
**
++
*
*
*
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 5 421
EFFECT OF VITAMIN E ON THE BLOOD-BRAIN BARRIER
Vitamin E was shown to decrease the intensity of
acute PTZ-sourced attacks in rats [20]. The levels
of this vitamin in the blood plasma of children
suffering from seizures were found to be lower than
the respective values in control children of the same
age [21]. Furthermore, an anti-attack effect of vitamin
E was observed under experimental conditions,
such as ferrous chloride model, hyperbaric oxygen
model, kindling, and PTZ-evoked seizure activity
[20, 22, 23].
In our study, a sufficiently high dose of vitamin E
demonstrated a clear protective effect against seizure-
related increase in the BBB permeability in old rats;
this was especially considerable with respect to the
cerebellum + brainstem regions of experimental
animals. This observation contradicts results of some
other studies were no protective effect of vitamin E on
epileptic attacks created by PTZ and other chemical
convulsants was found [24, 25]. These contradictions
are probably related to the fact that antioxidants
manifest dissimilar anticonvulsant effects depending
on the type of the convulsant or subeffective doses.
Vitamin E administered in 300 or 500 mg/kg doses was
shown to moderate the intensity of penicillin-sourced
epileptiform activity in rats [26]. As was mentioned
above, we found that this vitamin demonstrated a
protective effect against seizure-related disorders of
the BBB permeability in young and adult rats, and the
70 mg/kg dose was effective [12]. At the same time, it
is well-known that there are noticeable age-dependent
modifications of the epileptic and epileptiform activity
[27]. The threshold value for the attacks created by
PTZ introductions is higher in old animals, durations
of generalized attacks are longer in this age group than
in adults, and old animals are distinguished by a higher
relapse ratio [28, 29]. In this our study, we found that
the 70 mg/kg dose of vitamin E exerts practically no
protective effect on the BBB under conditions of PTZ-
induced seizures in aged rats; such an effect appears
only in the case of a much higher dose.
Alterations in the neuromodulatory systems
depending on aging constitute the most probable
reason for these dissimilarities. As was shown, these
systems regulate in vivo the epileptiform activity and
significantly influence the relapse severity, sensitivity,
and prevalence [30, 31]. Considerable modifications of
synaptic connections, electrotonic coupling, features
of receptors and channels, numbers and functions
of specific-type neurons within neuronal networks
develop due to aging [32-37]. Besides this, it was
reported that age-dependent alterations also develop
in the sodium/potassium equilibrium and extracellular
volume, and these alterations noticeably affect neuronal
synchronization and excitability [38-41]. Thus, much
higher doses of vitamin E are needed to provide its
protective effect against the increased permeability of
the BBB during epileptic attacks in old organism.
The fact that Evans Blue contents in the hemispheres
of rats in the PTZ + E70 group 3 were found to be not
lower but even somewhat higher than the respective
figures in group 2 (PTZ) may have two explanations.
First, this can result from an occasional deviation
mostly related to a high dispersion of this index in all
PTZ groups. Another interpretation, however, should
also be taken into account. Vitamin E, probably,
cannot be considered an "absolute" antioxidant. There
are indications that this vitamin is a redox reagent that
can, under certain conditions, function as a prooxidant
[42-45]. Thus, in some cases it probably can somewhat
increase the disturbed BBB permeability.
Х. Йорулмаз1, Ф. Бурку Секер2, Б. Озтаз3
ВПЛИВ ВІТАМІНУ Е НА ПРОНИКНІСТЬ ГЕМАТО-
ЕНЦЕФАЛІЧНОГО БАР’ЄРА У СТАРИХ ЩУРІВ З
ПЕНТИЛЕНТЕТРАЗОЛІНДУКОВАНИМИ СУДОМАМИ
1 Школа охорони здоров’я Халік, Університет Халік, Стам-
бул (Туреччина).
2 Університет Йедітепе, Стамбул (Туреччина).
3 Стамбульський університет (Туреччина).
Р е з ю м е
На старих (вік 23–24 місяці) самцях білих щурів дослід-
жували вплив вітаміну Е на розлади проникності гемато-
енцефалічного бар’єра (ГЕБ), пов’язані з розвитком
судомної активності, котра була індукована введенням пен-
тилентетразолу (ПТЗ); як трасер використовували барвник
Еванс блакитний. У тварин із ПТЗ-викликаними судома-
ми проникність ГЕБ значно збільшувалася; вміст барвни-
ка в тканинах лівої та правої мозкових півкуль, мозочка та
стовбура мозку вірогідно перевищував відповідні значення
в контролі. Вітамін Е в дозі 70 мг/кг практично не справ-
ляв позитивного впливу на збільшену проникність ГЕБ у
тварин із судомною активністю. Застосування ж вітамі-
ну Е в більших дозах (700 мг/кг) забезпечувало істотний
протективний ефект, особливо щодо зразків тканин мозоч-
ка та стовбура мозку (P < 0.01). Підвищення артеріально-
го кров’яного тиску, пов’язане з розвитком судом, в остан-
ній з експериментальних серій було помірнішим, ніж у двох
інших серіях. Отже, наші спостереження підтверджують
важливість дозування вітаміну Е як протективного фактора
щодо проникності ГЕБ та вказують на те, що залежність від
НЕЙРОФИЗИОЛОГИЯ / NEUROPHYSIOLOGY.—2010.—T. 42, № 5422
H. YORULMAZ, F. BURCU SEKER, and B. OZTAS
дози цього вітаміну, використовуваного як антиоксидант, у
старих тварин істотно відрізняється від такої у молодших
організмів.
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| id | nasplib_isofts_kiev_ua-123456789-68365 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 0028-2561 |
| language | English |
| last_indexed | 2025-12-02T11:20:14Z |
| publishDate | 2010 |
| publisher | Інститут фізіології ім. О.О. Богомольця НАН України |
| record_format | dspace |
| spelling | Yorulmaz, H. Burcu Seker, F. Oztas, B. 2014-09-21T17:55:55Z 2014-09-21T17:55:55Z 2010 Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions / H. Yorulmaz, F. Burcu Seker, B. Oztas // Нейрофизиология. — 2010. — Т. 42, № 5. — С. 418-423. — Бібліогр.: 45 назв. — англ. 0028-2561 https://nasplib.isofts.kiev.ua/handle/123456789/68365 612.82+612.825.3+576.161.3+612.67 The effect of vitamin E on the blood-brain barrier (BBB) permeability was studied under conditions of pentylenetetrazole (PTZ)-induced convulsions in aged (23- to 24-month-old) male albino rats; Evans Blue was used as a tracer. The BBB permeability was found to considerably increase in rats with PTZ-evoked seizures; the Evans Blue contents in the left and right hemispheres and cerebellum + brainstem region were significantly higher than those in the control. Vitamin E used in the dose of 70 mg/kg exerted practically no beneficial effect on the increased BBB permeability in rats with seizures, while a greater dose of vitamin E (700 mg/kg) exerted a significant protective effect, especially with respect to the cerebellum + brainstem regions (P < 0.01). The seizure-related rise in the arterial blood pressure was also smaller in the latter experimental group. Thus, our observations confirm the importance of the dose of vitamin E as a protective factor for the BBB permeability and demonstrate that the dose dependence of this antioxidant in aged animals dif fers from that in younger or ganisms. На старих (вік 23–24 місяці) самцях білих щурів досліджували вплив вітаміну Е на розлади проникності гематоенцефалічного бар’єра (ГЕБ), пов’язані з розвитком судомної активності, котра була індукована введенням пентилентетразолу (ПТЗ); як трасер використовували барвник Еванс блакитний. У тварин із ПТЗ-викликаними судомами проникність ГЕБ значно збільшувалася; вміст барвника в тканинах лівої та правої мозкових півкуль, мозочка та стовбура мозку вірогідно перевищував відповідні значення в контролі. Вітамін Е в дозі 70 мг/кг практично не справляв позитивного впливу на збільшену проникність ГЕБ у тварин із судомною активністю. Застосування ж вітаміну Е в більших дозах (700 мг/кг) забезпечувало істотний протективний ефект, особливо щодо зразків тканин мозочка та стовбура мозку (P < 0.01). Підвищення артеріального кров’яного тиску, пов’язане з розвитком судом, в останній з експериментальних серій було помірнішим, ніж у двох інших серіях. Отже, наші спостереження підтверджують важливість дозування вітаміну Е як протективного фактора щодо проникності ГЕБ та вказують на те, що залежність від дози цього вітаміну, використовуваного як антиоксидант, у старих тварин істотно відрізняється від такої у молодших організмів. en Інститут фізіології ім. О.О. Богомольця НАН України Нейрофизиология Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions Вплив вітаміну Е на проникність гемато-енцефалічного бар’єра у старих щурів з пентилентетразоліндукованими судомами Article published earlier |
| spellingShingle | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions Yorulmaz, H. Burcu Seker, F. Oztas, B. |
| title | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions |
| title_alt | Вплив вітаміну Е на проникність гемато-енцефалічного бар’єра у старих щурів з пентилентетразоліндукованими судомами |
| title_full | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions |
| title_fullStr | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions |
| title_full_unstemmed | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions |
| title_short | Effect of vitamin E on the blood-brain barrier permeability in aged rats with ptz-induced convulsions |
| title_sort | effect of vitamin e on the blood-brain barrier permeability in aged rats with ptz-induced convulsions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/68365 |
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