Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats

Rats i.p. injected once with 10 mg/kg kainic acid exhibited clear seizure behavior (“wet-dog
 shakes,” rearing on the hindlimbs, and bilateral clonus). Pretreatment with L-arginine (L-Arg
 twice a day for 5 days) significantly decreased these manifestations. The medium dose of&#x...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Нейрофизиология
Datum:2013
Hauptverfasser: Sun, Yi., Yin, Sh., Li, Sh., Yu, D., Gong, D., Xu, J., Lian, Yo, Sun, Ch
Format: Artikel
Sprache:Englisch
Veröffentlicht: Інститут фізіології ім. О.О. Богомольця НАН України 2013
Online Zugang:https://nasplib.isofts.kiev.ua/handle/123456789/148024
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Zitieren:Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats / Yi. Sun, Sh. Yin, Sh. Li, D. Yu, D. Gong, J. Xu, Yo. Lian, Ch. Sun // Нейрофизиология. — 2013. — Т. 45, № 1. — С. 25-30. — Бібліогр.: 28 назв. — англ.

Institution

Digital Library of Periodicals of National Academy of Sciences of Ukraine
_version_ 1860077499875065856
author Sun, Yi.
Yin, Sh.
Li, Sh.
Yu, D.
Gong, D.
Xu, J.
Lian, Yo
Sun, Ch
author_facet Sun, Yi.
Yin, Sh.
Li, Sh.
Yu, D.
Gong, D.
Xu, J.
Lian, Yo
Sun, Ch
citation_txt Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats / Yi. Sun, Sh. Yin, Sh. Li, D. Yu, D. Gong, J. Xu, Yo. Lian, Ch. Sun // Нейрофизиология. — 2013. — Т. 45, № 1. — С. 25-30. — Бібліогр.: 28 назв. — англ.
collection DSpace DC
container_title Нейрофизиология
description Rats i.p. injected once with 10 mg/kg kainic acid exhibited clear seizure behavior (“wet-dog
 shakes,” rearing on the hindlimbs, and bilateral clonus). Pretreatment with L-arginine (L-Arg
 twice a day for 5 days) significantly decreased these manifestations. The medium dose of
 L-Arg (40 mg/kg) was found to be close to optimum; 10 and 160 mg/kg L-Arg provided much
 smaller positive effects. In KA-treated rats, a much higher density of GFAP positive astrocytes was found in the hilus of the dorsal hippocampus, while 40 mg/kg L-Arg+KA-treated
 rats demonstrated noticeably weaker GFAP overexpression. The results of Western blotting
 analysis were fully comparable with those obtained in the immunostaining experiments. Поведінка щурів, яким внутрішньоочеревинно ін’єкували
 10 мг/кг каїнової кислоти (КК), характеризувалася вираженими проявами судом, „струшуваннями мокрого собаки”,
 вставанням на задні кінцівки та білатеральним клонусом.
 Попередні введення L-аргініну (L-Aрг) двічі на день протягом п’яти днів забезпечували істотне зменшення інтенсивності таких проявів. Було виявлено, що доза L-Aрг 40 мг/кг
 є близькою до оптимальної; дози 10 та 160 мг/кг справляли
 менш виражену позитивну дію. У щурів, яким уводили КК,
 у хілусі дорсального гіпокампа спостерігалася більш висока щільність астроцитів, імунопозитивних щодо гліального фібрилярного кислого білка (GFAР), у той час як у щурів, котрим уводили КК сумісно із 40 мг/кг L-Арг, експресія
 GFAP була виражена в помітно меншій мірі. Результати досліджень з використанням Вестерн-блотингу були повністю
 співставними з даними, отриманими в експериментах з імуногістологічним міченням.
first_indexed 2025-12-07T17:14:33Z
format Article
fulltext NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 1 25 UDC 616.853+577.112.85 Yi. SUN1, Sh. YIN2, Sh. LI1, D. YU2, D. GONG1, J. XU1, Yo. LIAN1, and Ch. SUN2 EFFECTS OF L-ARGININE ON SEIZURE BEHAVIOR AND EXPRESSION OF GFAP IN KAINIC ACID-TREATED RATS Received September 15, 2012. Rats i.p. injected once with 10 mg/kg kainic acid exhibited clear seizure behavior (“wet­dog shakes,” rearing on the hindlimbs, and bilateral clonus). Pretreatment with L­arginine (L­Arg twice a day for 5 days) significantly decreased these manifestations. The medium dose of L­Arg (40 mg/kg) was found to be close to optimum; 10 and 160 mg/kg L­Arg provided much smaller positive effects. In KA­treated rats, a much higher density of GFAP­positive astro­­positive astro­positive astro­ cytes was found in the hilus of the dorsal hippocampus, while 40 mg/kg L­Arg+KA­treated rats demonstrated noticeably weaker GFAP overexpression. The results of Western blotting analysis were fully comparable with those obtained in the immunostaining experiments. Keywords: L-arginine, kainic acid, seizure behavior, GFAP. 1 Department of Functions Physiology, Dalian Medical University, Dalian, China. 2 Institute for Brain Disorders, Dalian Medical University, Dalian, China. Correspondence should be addressed to Chang­kai Sun (e­mail: cksun110@vip.sina.com). INTRODUCTION L­Arginine (L­Arg) first isolated in 1886 is one of the 20 most common natural amino acids. In mammals, arginine is classified as a semiessential or conditionally essential amino acid (depending on the developmental stage and health status of the individual) [1]. Preterm infants are unable to synthesize arginine internally, making this amino acid nutritionally essential for them [2]. There are some conditions that cause increased requires of the organism for the synthesis of L­arginine, including surgical or other trauma, sepsis, and burns. It should be taken into consideration that L­Arg is the substrate for nitric oxide (NO) synthesis. Kainic acid (KA) is a natural organic acid existing in some seaweed. It is a specific agonist for the kainate receptors, a subtype of ionotropic glutamate receptors for which KA can imitate the effect of glutamate. Kainic acid is a potent stimulant of the CNS used for the induction of seizures in experimental animals; in particular, KA allows experimenters to build up a rat model of epilepsy. As was demonstrated earlier, NO may alleviate seizures and, thus, may be a kind of endogenous antiepileptics [3]. However, the mechanism of NO action in this respect still remains unclear. It has been reported that reactive proliferation of astrocytes occurs during the process of neurodegeneration or brain injury, and this is accompanied by intensification of the synthesis of glial fibrillary acidic protein (GFAP), a cell­specific marker for reactive astrocytes [4­6]. Increased GFAP immunoreactivity [7­8] and the respective mRNA levels were found in seizure­manifesting rats [9­11]. The question whether L­Arg, an important component of the NO system, exerts any effect on the expression of GFAP has not yet been clarified. This is why we investigated the effects of L­Arg on seizure behavior and expression of GFAP in KA­treated rats. METHODS Animals and Treatments. Male Wistar rats (mean body mass 230 ± 20 g) were obtained from the Experi­ mental Animal Center of the Dalian Medical Universi­ ty (China). Sixty animals were randomly selected and divided into six groups. Rats of three L­Arg­treated groups were i.p. injected with 10, 40, and 160 mg/kg L­Arg twice a day for 5 days, respectively. Animals the KA­treated group were i.p. injected with 10 mg/kg KA once on the 6th day after L­Arg pretreatment. The normal control and negative control groups were in­ jected with physiological saline (2 ml/kg) at the same time as the groups mentioned above. Behavioral Observations. All rats injected with 10 mg/kg KA demonstrated brisk rotational NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 126 Yi. SUN, Sh. YIN, Sh. LI et al. movements of the head and trunk called “wet dog shakes” (WDSs). The onset of seizures and the degree of their severity were estimated using a point scale proposed by Racine [12]: 1, chewing; 2, head nodding; 3, unilateral forelimb clonus; 4, rearing with bilateral forelimb clonus; and 5, rearing with bilateral forelimb clonus and falling back. Behavior of KA­treated rats was monitored for 3 h after KA administration. Immunohistostaining. After observing seizure behavior, the rats were i.p. anesthetized with pentobarbitone and perfused transcardially with 4% paraformaldehyde. The brains were removed and immersed in 20% sucrose diluted in 0.1 M phosphate­ buffered saline (PBS, pH 7.4). Brain samples were cut into 50­mm­thick slices. The latter were first rinsed in PBS for 10 min and then consequently incubated with bovine serum albumin (BSA) for 30 min, incubated with the primary GFAP antibody (1:3,000) overnight at 4°C, rinsed in PBS for 10 min, and then incubated with biotinylated goat anti­rabbit serum (1:500) and avidin­ biotin complex (ABC) for 3 h. Diaminobenzidine (DAB) provided visualization of staining. Control sections were incubated with PBS instead of the primary antibody. Pathological Image Analysis. A HPIAS series colorful pathology photograph system was used to analyze GFAP­immunopositive (ip) cells. The test­ squares in the screen of the microscope used were 194258 mm2, and the number and average optical density of GFAP­ip cells were measured within these squares. Western Blotting Analysis. Hippocampal samples were removed, weighed, homogenized in Tris buffer saline (TBS, pH 7.5) for 15 sec, and then vigorously vortexed for 10 sec. Parts of the homogenized samples (100 ml) were heated at 100°C for 5 min and then centrifuged at 13,000 rpm for 5 min. Ten microliters of the supernatant were used for quantifying protein according to the Smith’s method [11]. Another 100 ml of homogenized samples were added to an equal volume of the sample loading buffer, heated at 100°C for 5 min, and then centrifuged at 13,000 rpm for 5 min. After these procedures, electrophoresis, transferring, and identifying were carried out. Markers were cut away from the membrane, stained, destained, and dried, while the other part of the membrane was washed twice with TBS for 10 min and then immobilized by 1% BSA for 1 h. Next operations were incubation with the primary antibody against GFAP (1:1,500) and subsequent incubation with the secondary antibody and ABC for 1 h. Finally, photographs were taken and analyzed. Statistics. The numerical results are shown as means ± s.d., and the one­way ANOVA test was used to evaluate the statistical significance (P < 0.05). RESULTS Behavior. The KA­treated rats in the model group exhibited clear time­dependent seizure behavior. Five minutes after KA injection, staring and WDSs occurred during 30 min to 1 h. Spontaneous stereotyped seizure behavior happened within a 1­ to 3­h­long interval; this was characterized by rearing on the hindlimbs with bilateral clonus, until the balance was lost. In comparison with the control group, animals of the 160 mg L­Arg + 10 mg/kg KA­injected group showed much longer WDS latencies with no significant differences in the rearing latency and seizure scores. However, 40 mg/kg L­Arg + KA­treated rats showed much longer WDS latencies and rearing latencies with lower seizure scores, while 10 mg/kg L­Arg + KA­ treated group showed no significant changes. These results suggested that 10 mg/kg L­Arg could alleviate the normal condition only mildly, while 40 mg/kg L­Arg alleviated the condition obviously. This proved that the effect of L­Arg on abnormal behavior induced by KA is dose­dependent, and that the optimum dose of L­Arg is about 40 mg/kg, as illustrated in Table 1. Table 1. Effects of Different Doses of L-Arginine (L-Arg) on Kainic Acid (KA)-Induced Seizure Behavior in Rats Т а б л и ц я. 1. Вплив L-аргініну на прояви судом, викликаних дією каїнової кислоти Animal groups injected with different agents WDS latency, min Rearing latency, min Score of seizures 2 ml/kg PS+10 mg/kg KA 26.44 ± 1.21 77 ± 2.17 23.19 ± 0.83 10 mg/kg L­Arg +10 mg/kg KA 25.12 ± 1.06 76 ± 2.20 22.17±0.79 40 mg/kg L­Arg+ 10 mg/kg KA 33.75 ± 1.29** 90 ± 3.15** 16.25 ± 0.77** 160 mg/kg L­Arg + 10 mg/kg KA 34.62 ± 1.73** 89 ± 4.55 21.35 ± 0.63 Footnotes. **Significant difference from physiological saline (PS) + KA­injected group with P < 0.01 (n = 10). WDS) “Wet dog shakes” (brist rotational movements of the head and trunk). NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 1 27 EFFECTS OF L­ARGININE ON SEIZURE BEHAVIOR AND EXPRESSION OF GFAP Immunohistostaining Analysis. In comparison with the control group, the number and the density of GFAP­ip astrocytes in KA­treated rats were significantly greater in the hilus of the dorsal hippocampus. A bandlike distribution of astrocytes was clearly observed, the general intensity of staining of the GFAP­ip units was markedly greater, and strongly labeled immunoreactive elements were almost entirely located in the hilus and adjacent regions. A majority of the GFAP­ip cells appeared larger and were stained more heavily, with positive processes appearing more clearly. However, 40 mg/kg L­Arg + KA­treated rats demonstrated noticeably weaker overexpression of GFAP­ip astrocytes mentioned above; there was no statistically significant difference from the expression in the control groups (Fig. 1 and Table 2). TABLE 2. Numbers of GFAP-ip Astrocytes and Pathological Image Analysis in the Hilus of the Rat Dorsal Hippocampus Т а б л и ц я 2. Кількість GFAP-імунопозитивних астроцитів та прояви патологічних змін у хілусі дорсального гіпокампа щурів Animal groups injected with different agents N S, μm2 D ID 2 ml/kg PS 10.08 ± 0.93 402.74 ± 10.92 0.71 ± 0.01 375.74 ± 6.02 40 mg/kg L­Arg 10.17 ± 0.96 400.00 ± 16.81 0.70 ± 0.01 374.77 ± 7.04 2 ml/kg PS + + 10 mg/kg KA 14.13 ± 0.68** 715.42 ± 17.01** 0.90 ± 0.03* 610.29 ± 21.00** 40 mg/kg L­Arg + + 10 mg/kg KA 10.38 ± 0.56## 388.60 ± 12.68## 0.69 ± 0.01## 355.06 ± 14.32## Footnotes. N) Number of positive cells, S) surface area of the positive bodies, D) average optical density, and ID) integral optical density per one sight region (194,258 mm2, n = 15­20 sections). * Significant difference from the control PS­injected group at P < 0.05. ** Significant difference from the control PS­injected group at P < 0.01. ## Significant difference from the PS + KA­injected group at P < 0.01. Other designations are the same as in Table 1. F i g. 1. Effect of 40 mg/kg L­arginine (L­Arg) on expression of GFAP­ip astrocytes in the rat dorsal hippocampus. A­D) Hippocampal slices obtained from a control animal injected with physiological saline (2 ml/kg, A), a 10 mg/kg kainic acid (KA)­ treated rat (B), an L­Arg­injected animal (C), and a KA + L­Arg­treated animal. m and g) Molecular and granular layers of the dentate gyrus, respectively; h) hilus of the dentate gyrus, and p) stratum pyramidale of the CA3. Р и с. 1. Вплив 40 мг/кг L­аргініну на експресію гліального фібрилярного кислого протеїну (GFAP) в астроцитах дорсального гіпокампа щура. A C B D NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 128 Yi. SUN, Sh. YIN, Sh. LI et al. Western Blotting Analysis. The molecular mass of GFAP is about 50 kDa. Three hours after KA injec­ tion, GFAP expression was obviously more intense in the PS­treated + KA­injected group. At the same time, such expression in the 40 mg/kg L­Arg + KA­rats was noticeably weaker and showed no significant dif­ ference vs that in the PS­injected group (Figs. 2 and 3). These results are fully comparable with those ob­ tained in the immunohistostaining experiments. DISCUSSION Nitric oxide has been implicated in mediation of neuronal excitotoxic injury [14­15]. L­arginine (the substrate for NO synthesis), regarded as the main endogenous source for NO production, was used in our experiments to study the role of NO in generation of seizures in KA­treated rats. It was reported earlier that pretreatment with L­Arg tends to potentiate the effects of quinolinic acid (QA) and induces clonic and tonic convulsions in mice [16]. Simultaneously, the effects of L­Arg on seizure activity elicited by KA are dose­dependent and contribute to the genesis of seizure activity [17]. At the same time, it was found that L­Arg did not affect kindling or seizure severity [18]. Other studies showed that NO might act as an endogenous anticonvulsant in mice [19­20], and the anticonvulsant L­Arg alone significantly increases the NO concentration and NOS activity in specific brain regions responsible for suppression of convulsions [21­22]. Previous studies, however, indicated that KA­induced seizures appeared later in rats pretreated with a single large dose of L­Arg [18­21]. Due to all the above­mentioned controversies, we investigated the effects of chronic treatment with small doses of L­Arg on KA­induced seizures. The results showed that pretreatment with 40 mg/kg L­Arg clearly alleviated KA­induced seizures, while pretreatment with the lower (10 mg/kg) or greater (160 mg/kg) doses of L­Arg demonstrated less significant effects. Thus, the dose dependence is probably U­like. We also observed that chronic treatment with moderate doses of L­Arg (40 mg/kg) exhibited anticonvulsant effects. The results presented here indicate that chronic treatment with moderate doses of L­Arg (40 mg/kg) provide an anticonvulsant action, but the mechanism of such effect still remains unclear. Astrocytes perform a variety of functions in the adult CNS [23­ 24]. Reactive gliosis is a response of astrocytes to a variety of insults that is characterized by hypertrophy A B C D S 1600 1400 1200 1000 800 600 400 200 0 PS L-Arg PS+KA L-Arg+KA F i g. 2. Expression of GFAP in the rat hippocampus demonstrated using Western blot analysis. A) Control (physiological saline­ injected) group, B) KA­treated rats, C) 40 mg/kg L­Arg­injected animals, and D) KA + 40 mg/kg L­Arg­treated group. S) Standard molecular mass (kDa) of the markers, from top to bottom, 97.4 (phosphorylase), 66.2 (bovine serum albumin), 55.0 (glutamate dehydrogenase), 42.7 (ovalbumin), and 40.0 (aldolase). Each lane showes an identical major band stained strongly at about 50 kDa position. Р и с. 2. Експресія GFAP у гіпокампі щурів: результати Вестерн­ блотингу. F i g. 3. Results of scanning of hippocampal GFAP expression (n = 6). L­Arg) L­arginine, KA) kainac acid. * Significant difference from the control physiological saline­injected group (PS) at P < 0.05. + Significant difference from PS + KA­treated group at P < 0.05. Vertical scale) Relative optical density. Р и с. 3. Результати сканування при дослідженні експресії GFAP у гіпокампі щурів. Actin NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 1 29 EFFECTS OF L­ARGININE ON SEIZURE BEHAVIOR AND EXPRESSION OF GFAP of the cell bodies and processes and an increase in the expression of GFAP [25­26]. Previous studies revealed that a single convulsive KA­induced seizure episode strongly intensifies GFAP expression in astrocytes in the hippocampal formation. Bennett et al. reported that GFAP immunopositivity was enhanced in the hippocampus and correlative brain areas 3 h after KA injection, but the specific distribution and alteration were not described [27, 28]. Our results showed that GFAP expression after L­Arg pretreatment reduced KA­challenged seizure behavior. Furhtermore, L­Arg pretreatment with the dosage of 40 mg/kg inhibited hyperplasia and hypertrophy of the astrocytes and bandlike distribution of these glial cells and also alleviated the abnormal overexpression of GFAP induced by KA. Thus, our study suggests that the effect of NO on KA­induced seizures is dose­dependent, and that the L­Arg dose of 40 mg/kg seems to be optimum for correction of KA­induced abnormal behavior. The effect may be related to regulation of the expression of GFAP and to a protecting action with respect to astrocytes. In future, we will try to block NO expression and to observe behavioral changes and changes in astrocytes in KA­treated animals. It is necessary to be sure that NO is the key point for curing KA­induced seizures and to make clear the possible mechanism of the action of the optimum L­Arg dose (40 mg/kg), which most effectively reduced abnormal behavior in KA­treated rats. Йї. Сун1, Ш. Йїн2, Ш. Лі1, Д. Ю, Д. Гон1, Дж. Ксу1, Йо. Ліан1, Ч. Сун2 ВПЛИВИ L­АРГІНІНУ НА СУДОМНІ ПОВЕДІНКОВІ ПРОЯВИ ТА ЕКСПРЕСІЮ GFAP, ЗУМОВЛЕНІ ВВЕДЕН­GFAP, ЗУМОВЛЕНІ ВВЕДЕН­, ЗУМОВЛЕНІ ВВЕДЕН­ НЯМ КАЇНОВОЇ КИСЛОТИ ЩУРАМ 1 Далянський медичний університет (Китай). 2 Інститут із дослідження патології мозку Далянського ме­ дичного університету (Китай). Р е з ю м е Поведінка щурів, яким внутрішньоочеревинно ін’єкували 10 мг/кг каїнової кислоти (КК), характеризувалася вираже­ ними проявами судом, „струшуваннями мокрого собаки”, вставанням на задні кінцівки та білатеральним клонусом. Попередні введення L­аргініну (L­Aрг) двічі на день протя­ гом п’яти днів забезпечували істотне зменшення інтенсив­ ності таких проявів. Було виявлено, що доза L­Aрг 40 мг/кг є близькою до оптимальної; дози 10 та 160 мг/кг справляли менш виражену позитивну дію. У щурів, яким уводили КК, у хілусі дорсального гіпокампа спостерігалася більш висо­ ка щільність астроцитів, імунопозитивних щодо гліально­ го фібрилярного кислого білка (GFAР), у той час як у щу­ рів, котрим уводили КК сумісно із 40 мг/кг L­Арг, експресія GFAP була виражена в помітно меншій мірі. Результати до­ сліджень з використанням Вестерн­блотингу були повністю співставними з даними, отриманими в експериментах з іму­ ногістологічним міченням. REFERENCES 1. H. Tapiero, G. Mathé, P. Couvreur, and K. D. Tew, “I. Arginine,” Biomed. Pharmacother., 56, No. 9, 439­445 (2002). 2. G. Wu, L. A. Jaeger, F. W. Bazer, and J. M. Rhoads, “Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications,” J. Nutr. Biochem., 15, No. 8, 442­ 451 (2004). 3. Y. P. Sun, C. K. Sun, M. Fan, et al., “Effect of NO mediator on kainic acid­induced behavioral seizures in rats,” Chin. J. Appl. Physiol. (in Chinese), 19, Issue 2, 185­188 (2003). 4. J. B. Gramsbergen and K. J. van den Berg, “Regional and temporal profiles of calcium accumulation and glial fibrillary acidic protein levels in rat brain after systemic injection of kainic acid,” Brain Res., 667, No. 2, 216­228 (1994) 5. B. Adams, L. E. Von, and L. Vaccarella, “Time course for kindling­induced changes in the hilar area of the dentate gyrus: reactive gliosis as a potential mechanism,” Brain Res., 804, No. 2, 331­336 (1998). 6. P. Santofimia­Castaño, G. M. Salido, and A. Gonzalez, “Ethanol reduces kainate­evoked glutamate secretion in rat hippocampal astrocytes,” Brain Res., 1402, 1­8 (2011). 7. M. Carballo­Quintás, I. Martínez­Silva, C. Cadarso­Suárez, et al., “A study of neurotoxic biomarkers, c­Fos and GFAP, after acute exposure to GSM radiation at 900 MHz in the picrotoxin model of rat brains,” Neurotoxicology, 32, No. 4, 478­494 (2011). 8. Y.­P. Sun, W.­Q. Zhang, and J.­S. Hong, “The changes of glial fibrillary acidic protein(GFAP)­immunoreactivity in the seizure sensitive rat brain,” Chin. J. Neurosci. (in Chinese), 3, No. 2, 73­78 (1996). 9. E. R. Torre, E. Lothman, and O. Steward, “Glial response to neuronal activity: GFAP­mRNA and protein levels are transiently increased in the hippocampus after seizures,” Brain Res., 631, No. 2, 256­264 (1993). 10. O. Steward, “Electroconvulsive seizures upregulate astroglial gene expression selectively in the dentate gyrus,” Mol. Brain Res., 25, Nos. 3/4, 217­224 (1994). 11. L. C. V. Baille and J. M. Collombet, “Early regional changes of GFAP mRNA in rat hippocampus and dentate gyrus during soman­induced seizures,” NeuroReport, 7, No. 1, 365­369 (1995). 12. R. J. Racine, “Modification of seizure activity by electrical stimulation,” Electroencephalogr. Clin. Neurophysiol., 32, No. 3, 281­294 (1972). 13. M. J. Dunn, “Determination of total protein concentration,” in: Protein Purification Methods. A Practical Approach, IRL Press, Oxford (1989), pp. 10­18. 14. A. Lumme, S. Soinila, M. Sadeniemi, et al., “Nitric oxide synthase immunoreactivity in the rat hippocampus after status NEUROPHYSIOLOGY / НЕЙРОФИЗИОЛОГИЯ.—2013.—T. 45, № 130 Yi. SUN, Sh. YIN, Sh. LI et al. epilepticus induced by perforant pathway stimulation,” Brain Res., 871, No. 2, 303­310 (2000). 15. L. Zhou and D. Y. Zhu, “Neuronal nitric oxide synthase: Structure, subcellular localization, regulation, and clinical implications,” Nitric Oxide, 20, No. 4, 223­230 (2009). 16. T. A. Nakamura, K. Yamada, T. Hasegawa, and T. Nabeshima, “Possible involvement of nitric oxide in quinolinic acid­ induced convulsion in mice,” Pharmacol. Biochem. Behav., 51, Nos. 2/3, 309­312 (1995). 17. G. De Sarro, E. D. Di Paola, A. De Sarro, and M. J. Vidal, “L­arginine potentiates excitatory amino acid­induced seizures elicited in the deep prepiriform cortex,” Eur. J. Pharmacol., 230, No. 2, 151­158 (1993). 18. L. J. Herberg, A. Grottick, and I. C. Rose, ”Nitric oxide synthesis, epileptic seizures and kindling,” Psychopharmacology, 119, No. 1, 115­123 (1995). 19. E. Przegalinski, L. Baran, and J. Siwanowicz, “The role of nitric oxide in the kainate­induced seizures in mice,” Neurosci. Lett., 170, No. 1, 74­76 (1994). 20. A. Lesani, M. Javadi­Paydar, T. K. Khodadad, et al., “Involvement of the nitric oxide pathway in the anticonvulsant effect of tramadol on pentylenetetrazole­induced seizures in mice,” Epilepsy Behav., 19, No. 3, 290­295 (2010). 21. A. R. Jayakumar, R. Sujatha, V. Paul, et al., “Involvement of nitric oxide and nitric oxide synthase activity in anticonvulsive action,” Brain Res., 48, No. 4, 387­394 (1999). 22. A. Bahremand, P. Ziai, T. K. Khodadad, et al., “Agmatine enhances the anticonvulsant effect of lithium chloride on pentylenetetrazole­induced seizures in mice: Involvement of L­arginine/nitric oxide pathway,” Epilepsy Behav., 18, No. 3, 186­192 (1010). 23. N. Otani, H. Nawashiro, N. Nomura, et al., “A role of glial fibrillary acidic protein in hippocampal degeneration after cerebral trauma or kainate­induced seizure,” Acta Neurochir., Suppl., 86, 267­269 (2003). 24. A. Sharif and V. Prevot, “ErbB receptor signaling in astrocytes: A mediator of neuron­glia communication in the mature central nervous system,” Neurochem. Int., 57, No. 4, 344­358 (2010). 25. J. L. Stringer, “Repeated seizures increase GFAP and vimentin in the hippocampus,” Brain Res., 717, Nos. 1/2, 147­153 (1996). 26. T. Sawaguchi, F. Patricia, H. Kadhim, et al., “Clinicopathological correlation between brainstem gliosis using GFAP as a marker and sleep apnea in the sudden infant death syndrome,” Early Human Dev., 75, Suppl., S3­11 (2003). 27. S. A. Bennett, B. Stevenson, W. A. Staines, and D. C. Roberts, “Periodic acid­Schiff (PAS)­positive deposits in brain following kainic acid­induced seizures: relationships to fos induction, neuronal necrosis, reactive gliosis, and blood­brain barrier breakdown,” Acta Neuropathol., 89, No. 2, 126­138 (1995). 28. N. Otani, H. Nawashiro, S. Fukui, et al., “Enhanced hippocampal neurodegeneration after traumatic or kainite excitotoxicity in GFAP­null mice,” J. Clin. Neurosci., 13, No. 9, 934­938 (2006).
id nasplib_isofts_kiev_ua-123456789-148024
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
issn 0028-2561
language English
last_indexed 2025-12-07T17:14:33Z
publishDate 2013
publisher Інститут фізіології ім. О.О. Богомольця НАН України
record_format dspace
spelling Sun, Yi.
Yin, Sh.
Li, Sh.
Yu, D.
Gong, D.
Xu, J.
Lian, Yo
Sun, Ch
2019-02-16T17:44:36Z
2019-02-16T17:44:36Z
2013
Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats / Yi. Sun, Sh. Yin, Sh. Li, D. Yu, D. Gong, J. Xu, Yo. Lian, Ch. Sun // Нейрофизиология. — 2013. — Т. 45, № 1. — С. 25-30. — Бібліогр.: 28 назв. — англ.
0028-2561
https://nasplib.isofts.kiev.ua/handle/123456789/148024
Rats i.p. injected once with 10 mg/kg kainic acid exhibited clear seizure behavior (“wet-dog&#xd; shakes,” rearing on the hindlimbs, and bilateral clonus). Pretreatment with L-arginine (L-Arg&#xd; twice a day for 5 days) significantly decreased these manifestations. The medium dose of&#xd; L-Arg (40 mg/kg) was found to be close to optimum; 10 and 160 mg/kg L-Arg provided much&#xd; smaller positive effects. In KA-treated rats, a much higher density of GFAP positive astrocytes was found in the hilus of the dorsal hippocampus, while 40 mg/kg L-Arg+KA-treated&#xd; rats demonstrated noticeably weaker GFAP overexpression. The results of Western blotting&#xd; analysis were fully comparable with those obtained in the immunostaining experiments.
Поведінка щурів, яким внутрішньоочеревинно ін’єкували&#xd; 10 мг/кг каїнової кислоти (КК), характеризувалася вираженими проявами судом, „струшуваннями мокрого собаки”,&#xd; вставанням на задні кінцівки та білатеральним клонусом.&#xd; Попередні введення L-аргініну (L-Aрг) двічі на день протягом п’яти днів забезпечували істотне зменшення інтенсивності таких проявів. Було виявлено, що доза L-Aрг 40 мг/кг&#xd; є близькою до оптимальної; дози 10 та 160 мг/кг справляли&#xd; менш виражену позитивну дію. У щурів, яким уводили КК,&#xd; у хілусі дорсального гіпокампа спостерігалася більш висока щільність астроцитів, імунопозитивних щодо гліального фібрилярного кислого білка (GFAР), у той час як у щурів, котрим уводили КК сумісно із 40 мг/кг L-Арг, експресія&#xd; GFAP була виражена в помітно меншій мірі. Результати досліджень з використанням Вестерн-блотингу були повністю&#xd; співставними з даними, отриманими в експериментах з імуногістологічним міченням.
en
Інститут фізіології ім. О.О. Богомольця НАН України
Нейрофизиология
Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
Впливи L-аргініну на судомні поведінкові прояви та експресію GFAP, зумовлені введенням каїнової кислоти щурам
Article
published earlier
spellingShingle Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
Sun, Yi.
Yin, Sh.
Li, Sh.
Yu, D.
Gong, D.
Xu, J.
Lian, Yo
Sun, Ch
title Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
title_alt Впливи L-аргініну на судомні поведінкові прояви та експресію GFAP, зумовлені введенням каїнової кислоти щурам
title_full Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
title_fullStr Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
title_full_unstemmed Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
title_short Effects of L-Arginine on Seizure Behavior and Expression of GFAP in Kainic Acid-Treated Rats
title_sort effects of l-arginine on seizure behavior and expression of gfap in kainic acid-treated rats
url https://nasplib.isofts.kiev.ua/handle/123456789/148024
work_keys_str_mv AT sunyi effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT yinsh effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT lish effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT yud effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT gongd effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT xuj effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT lianyo effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT sunch effectsoflarginineonseizurebehaviorandexpressionofgfapinkainicacidtreatedrats
AT sunyi vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT yinsh vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT lish vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT yud vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT gongd vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT xuj vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT lianyo vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram
AT sunch vplivilargínínunasudomnípovedínkovíproâvitaekspresíûgfapzumovlenívvedennâmkaínovoíkislotiŝuram