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1.
Molecules ; 26(18)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34576901

RESUMO

Transient ischemia in brains causes neuronal damage, gliosis, and blood-brain barrier (BBB) breakdown, which is related to ischemia-induced brain dysfunction. Populus species have various pharmacological properties including antioxidant and anti-inflammatory activities. In this study, we found that phenolic compounds were rich in Populus tomentiglandulosa extract and examined the effects of Populus tomentiglandulosa extract on neuronal damage/death, astrogliosis, and BBB breakdown in the striatum, which is related to motor behavior, following 15-min transient ischemia in the forebrain in gerbils. The gerbils were pre-treated with 50, 100, and 200 mg/kg of the extract. The latter showed significant effects against ischemia-reperfusion injury. Ischemia-induced hyperactivity using spontaneous motor activity test was significantly attenuated by the treatment. Striatal cells (neurons) were dead at five days after the ischemia; however, pre-treatment with the extract protected the striatal cells from ischemia/reperfusion injury. Ischemia-induced reactive astrogliosis was significantly alleviated, in particular, astrocyte end feet, which are a component of BBB, were significantly preserved. Immunoglobulin G, which is not found in intact brain parenchyma, was apparently shown (an indicator of extravasation) in striatal parenchyma at five days after the ischemia, but IgG leakage was dramatically attenuated in the parenchyma by the pre-treatment. Based on these findings, we suggest that Populus tomentiglandulosa extract rich in phenolic compounds can be employed as a pharmaceutical composition to develop a preventive material against brain ischemic injury.

2.
Biology (Basel) ; 10(8)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34439951

RESUMO

Inadequate activation of cell cycle proteins including cyclin D1 and cdk4 is involved in neuronal cell death induced by diverse pathological stresses, including transient global brain ischemia. The neuroprotective effect of ischemic preconditioning is well-established, but the underlying mechanism is still unknown. In this study, we examined changes in cyclin D1, cdk4, and related molecules in cells or neurons located in Cornu Ammonis 1 (CA1) of gerbil hippocampus after transient ischemia for 5 min (ischemia and reperfusion) and investigated the effects of IPC on these molecules after ischemia. Four groups were used in this study as follows: sham group, ischemia group, IPC plus (+) sham group, and IPC+ischemia group. IPC was developed by inducing 2-min ischemia at 24 h before 5-min ischemia (real ischemia). Most pyramidal cells located in CA1 of the ischemia group died five days after ischemia. CA1 pyramidal cells in the IPC+ischemia group were protected. In the ischemia group, the expressions of cyclin D1, cdk4, phosphorylated retinoblastoma (p-Rb), and E2F1 (a transcription factor regulated by p-Rb) were significantly altered in the pyramidal cells with time after ischemia; in the IPC+ischemia group, they were controlled at the level shown in the sham group. In particular, the expression of p16INK4a (an endogenous cdk inhibitor) in the ischemia group was reversely altered in the pyramidal cells; in the IPC+TI group, the expression of p16INK4a was not different from that shown in the sham group. Our current results indicate that cyclin D1/cdk4-related signals may have important roles in events in neurons related to damage/death following ischemia and reperfusion. In particular, the preservation of p16INK4a by IPC may be crucial in attenuating neuronal death/damage or protecting neurons after brain ischemic insults.

3.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361744

RESUMO

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.


Assuntos
Anti-Inflamatórios/farmacologia , Isquemia Encefálica/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pinus/química , Prosencéfalo/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Flavonoides/química , Flavonoides/farmacologia , Expressão Gênica/efeitos dos fármacos , Gerbillinae , Hipocampo/metabolismo , Hipocampo/patologia , Inflamação , Interleucina-13/agonistas , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-4/agonistas , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Fármacos Neuroprotetores/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polifenóis/química , Polifenóis/farmacologia , Proantocianidinas/química , Proantocianidinas/farmacologia , Prosencéfalo/metabolismo , Prosencéfalo/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/patologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
4.
Lab Anim Res ; 37(1): 16, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261545

RESUMO

BACKGROUND: Hypothermic treatment is known to protect organs against cardiac arrest (CA) and improves survival rate. However, few studies have evaluated the effects of hypothermia on CA-induced liver damages. This study was designed to analyzed the possible protective effects of hypothermia on the liver after asphyxial CA (ACA). Rats were randomly subjected to 5 min of ACA followed by return of spontaneous circulation (ROSC). Body temperature was controlled at 37 ± 0.5 °C (normothermia group) or 33 ± 0.5 °C (hypothermia group) for 4 h after ROSC. Liver tissues were extracted and examined at 6 h, 12 h, 1 day, and 2 days after ROSC. RESULTS: The expression of infiltrated neutrophil marker CD11b and matrix metallopeptidase-9 (MMP9) was investigated via immunohistochemistry. Morphological damage was assessed via hematoxylin and eosin (H & E) staining. Hypothermic treatment improved the survival rate at 6 h, 12 h, 1 day, and 2 days after ACA. Based on immunohistochemical analysis, the expression of CD11b and MMP9 was significantly increased from 6 h after ACA in the normothermia group. However, the expressions of CD11b and MMP9 was significantly decreased in the hypothermia group compared with that of the normothermia group. In addition, in the results of H & E, sinusoidal dilatation and vacuolization were apparent after ACA; however, these ACA-induced structural changes were reduced by the 4 h-long hypothermia. CONCLUSIONS: In conclusion, hypothermic treatment for 4 h inhibited the increases in CD11b and MMP9 expression and reduced the morphological damages in the liver following ACA in rats. This study suggests that hypothermic treatment after ACA reduces liver damages by regulating the expression of CD11b and MMP9.

5.
Mol Med Rep ; 24(3)2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34212986

RESUMO

Tumor necrosis factor (TNF)­α and TNF receptor 1 (TNF­R1) play diverse roles in modulating the neuronal damage induced by cerebral ischemia. The present study compared the time­dependent changes of TNF­α and TNF­R1 protein expression levels in the hippocampal subfield cornu ammonis 1 (CA1) between adult and young gerbils following transient forebrain ischemia (tFI), via western blot and immunohistochemistry analyses. In adult gerbils, delayed neuronal death of pyramidal neurons, the principal neurons in CA1, was recorded 4 days after tFI; however, in young gerbils, delayed neuronal death was recorded 7 days after tFI. TNF­α protein expression levels gradually increased in both groups following tFI; however, TNF­α expression was higher in young gerbils compared with adult gerbils. TNF­R1 protein expression levels markedly increased in both groups 1 day after tFI. Subsequently, TNF­R1 expression gradually decreased in young gerbils, whereas TNF­R1 expression levels were irregularly altered in adult gerbils following tFI. Notably, TNF­α immunoreactivity significantly increased in pyramidal neurons in both groups 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF­α immunoreactivity was rarely exhibited in pyramidal neurons 4 days after tFI due to neuronal death, suggesting that TNF­α immunoreactivity was newly expressed in astrocytes. In young gerbils, TNF­α immunoreactivity increased in pyramidal neurons 4 days after tFI, and TNF­α immunoreactivity was newly expressed in astrocytes. In addition, TNF­R1 immunoreactivity was exhibited in pyramidal cells of both sham groups, and significantly increased 1 day after tFI; however, the patterns altered between both groups. In adult gerbils, TNF­R1 immunoreactivity was rarely exhibited 4 days after tFI, and astrocytes newly expressed TNF­R1 immunoreactivity. In young gerbils, TNF­R1 immunoreactivity increased in pyramidal neurons 4 days after tFI; however, TNF­R1 immunoreactivity was not reported in pyramidal neurons and astrocytes thereafter. Taken together, the results of the present study suggest that different expression levels of TNF­α and TNF­R1 in ischemic CA1 between adult and young gerbils may be due to age­dependent differences of tFI­induced neuronal death.

6.
Neurochem Res ; 46(11): 2852-2866, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34050880

RESUMO

Transient ischemia in the brain causes blood-brain barrier (BBB) breakdown and dysfunction, which is related to ischemia-induced neuronal damage. Leakage of plasma proteins following transient ischemia is one of the indicators that is used to determine the extent of BBB dysfunction. In this study, neuronal damage/death, leakage of albumin and IgG, microgliosis, and inflammatory cytokine expression were examined in the hippocampal CA1 region, which is vulnerable to transient ischemia, following 5-min (mild) and 15-min (severe) ischemia in gerbils induced by transient common carotid arteries occlusion (tCCAo). tCCAo-induced neuronal damage/death occurred earlier and was more severe after 15-min tCCAo vs. after 5-min tCCAo. Significant albumin and IgG leakage (albumin and IgG immunoreactivity) took 1 or 2 days to begin, and immunoreactivity was markedly increased 5 days after 5-min tCCAo. While, albumin and IgG leakage began to increase 6 h after 15-min tCCAo and remained significantly higher over time than that seen in 5-min tCCAo. IgG immunoreactivity was observed in degenerating neurons and activated microglia after tCCAo, and microglia were activated to a greater extent after 15-min tCCAo than 5-min tCCAo. In addition, following 15-min tCCAo, pro-inflammatory cytokines [tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß)] immunoreactivity was significantly higher than that seen following 5-min tCCAo, whereas immunoreactivity of anti-inflammatory cytokines (IL-4 and IL-13) was lower in 15-min than 5-min tCCAo. These results indicate that duration of tCCAo differentially affects the timing and degree of neuronal damage or loss, albumin and IgG leakage and inflammatory cytokine expression in brain tissue. In addition, more severe BBB leakage is closely related to acceleration of neuronal damage through increased microglial activation and pro-inflammatory cytokine expression in the ischemic hippocampal CA1 region.

7.
Exp Ther Med ; 21(6): 626, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33968162

RESUMO

Hypothermic treatment is known to protect against cardiac arrest (CA) and improve survival rate. However, few studies have evaluated the CA-induced liver damage and the effects of hypothermia on this damage. Therefore, the aim of the present study was to determine possible protective effects of hypothermia on the liver after asphyxial CA. Rats were subjected to a 5-min asphyxial CA followed by return of spontaneous circulation (ROSC). The body temperature was controlled at 37±0.5˚C (normothermia group) or 33±0.5˚C (hypothermia group) for 4 h after ROSC. Livers were examined at 6, 12 h, 1 and 2 days after ROSC. Histopathological examination was performed by H&E staining. Alterations in the expression levels of pro-inflammatory (TNF-α and interleukin IL-2) and anti-inflammatory cytokines (IL-4 and IL-13) were investigated by immunohistochemistry. Sinusoidal dilatation and vacuolization were observed after asphyxial CA by histopathological examination. However, these CA-induced structural alterations were prevented by hypothermia. In immunohistochemical examination, the expression levels of pro-inflammatory cytokines were reduced in the hypothermia group compared with those in the normothermia group while the expression levels of anti-inflammatory cytokines were increased in the hypothermia group compared with those in the normothermia group. In conclusion, hypothermic treatment for 4 h following asphyxial CA in rats inhibited the increase of pro-inflammatory cytokines and stimulated the expression of anti-inflammatory cytokines compared with the normothermic group. The results of the present study suggested that hypothermic treatment after asphyxial CA reduced liver damage via the regulation of inflammation.

8.
Int J Mol Sci ; 22(8)2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33921375

RESUMO

It has been studied that the damage or death of neurons in the hippocampus is different according to hippocampal subregions, cornu ammonis 1-3 (CA1-3), after transient ischemia in the forebrain, showing that pyramidal neurons located in the subfield CA1 (CA1) are most vulnerable to this ischemia. Hyperthermia is a proven risk factor for brain ischemia and can develop more severe and extensive brain damage related with mortality rate. It is well known that heme oxygenase-1 (HO-1) activity and expression is increased by various stimuli in the brain, including hyperthermia. HO-1 can be either protective or deleterious in the central nervous system, and its roles depend on the expression levels of enzymes. In this study, we investigated the effects of hyperthermia during ischemia on HO-1 expression and neuronal damage/death in the hippocampus to examine the relationship between HO-1 and neuronal damage/death following 5-min transient ischemia in the forebrain using gerbils. Gerbils were assigned to four groups: (1) sham-operated gerbils with normothermia (Normo + sham group); (2) ischemia-operated gerbils with normothermia (Normo + ischemia group); (3) sham-operated gerbils with hyperthermia (39.5 ± 0.2 °C) during ischemia (Hyper + sham group); and (4) ischemia-operated gerbils with hyperthermia during ischemia (Hyper + ischemia group). HO-1 expression levels in CA1-3 of the Hyper + ischemia group were significantly higher than those in the Normo + ischemia group. HO-1 immunoreactivity in the Hyper + ischemia group was significantly increased in pyramidal neurons and astrocytes with time after ischemia, and the immunoreactivity was significantly higher than that in the Normo + ischemia group. In the Normo + Ischemia group, neuronal death was shown in pyramidal neurons located only in CA1 at 5 days after ischemia. However, in the Hyper + ischemia group, pyramidal neuronal death occurred in CA1-3 at 2 days after ischemia. Taken together, our findings showed that brain ischemic insult during hyperthermic condition brings up earlier and severer neuronal damage/death in the hippocampus, showing that HO-1 expression in neurons and astrocytes is different according to brain subregions and temperature condition. Based on these findings, we suggest that hyperthermia in patients with ischemic stroke must be taken into the consideration in the therapy.


Assuntos
Lesões Encefálicas/genética , Heme Oxigenase-1/genética , Hipocampo/metabolismo , Traumatismo por Reperfusão/genética , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Gerbillinae/genética , Gerbillinae/metabolismo , Hipocampo/lesões , Hipocampo/fisiopatologia , Células Piramidais/metabolismo , Células Piramidais/patologia , Traumatismo por Reperfusão/patologia
9.
Antioxidants (Basel) ; 10(4)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33924188

RESUMO

Salicin is a major natural compound of willow bark and displays diverse beneficial biological properties, such as antioxidant activity. However, little information available for the neuroprotective potential of salicin against ischemic brain injury has been reported. Thus, this study was performed to investigate the neuroprotective potential of salicin against ischemia and reperfusion (IR) injury and its mechanisms in the hippocampus using a gerbil model of 5-min transient ischemia (TI) in the forebrain, in which a massive loss (death) of pyramidal neurons cells occurred in the subfield Cornu Ammonis 1 (CA1) among the hippocampal subregions (CA1-3) at 5 days after TI. To examine neuroprotection by salicin, gerbils were pretreated with salicin alone or together with LY294002, which is a phosphatidylinositol 3-kinase (PI3K) inhibitor, once daily for 3 days before TI. Treatment with 20 mg/kg of salicin significantly protected CA1 pyramidal neurons against the ischemic injury. Treatment with 20 mg/kg of salicin significantly reduced the TI-induced increase in superoxide anion generation and lipid peroxidation in the CA1 pyramidal neurons after TI. The treatment also reinstated the TI-induced decrease in superoxide dismutases (SOD1 and SOD2), catalase, and glutathione peroxidase in the CA1 pyramidal cells after TI. Moreover, salicin treatment significantly elevated the levels of phosphorylation of Akt and glycogen synthase kinase-3ß (GSK3ß), which is a major downstream target of PI3K, in the ischemic CA1. Notably, the neuroprotective effect of salicin was abolished by LY294002. Taken together, these findings clearly indicate that salicin protects against ischemic brain injury by attenuating oxidative stress and activating the PI3K/Akt/GSK3ß pathway.

10.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918660

RESUMO

Angelica gigas Nakai root contains decursin which exerts beneficial properties such as anti-amnesic and anti-inflammatory activities. Until now, however, the neuroprotective effects of decursin against transient ischemic injury in the forebrain have been insufficiently investigated. Here, we revealed that post-treatment with decursin and the root extract saved pyramidal neurons in the hippocampus following transient ischemia for 5 min in gerbil forebrain. Through high-performance liquid chromatography, we defined that decursin was contained in the extract as 7.3 ± 0.2%. Based on this, we post-treated with 350 mg/kg of extract, which is the corresponding dosage of 25 mg/kg of decursin that exerted neuroprotection in gerbil hippocampus against the ischemia. In addition, behavioral tests were conducted to evaluate ischemia-induced dysfunctions via tests of spatial memory (by the 8-arm radial maze test) and learning memory (by the passive avoidance test), and post-treatment with the extract and decursin attenuated ischemia-induced memory impairments. Furthermore, we carried out histochemistry, immunohistochemistry, and double immunohistofluorescence. Pyramidal neurons located in the subfield cornu ammonis 1 (CA1) among the hippocampal subfields were dead at 5 days after the ischemia; however, treatment with the extract and decursin saved the pyramidal neurons after ischemia. Immunoglobulin G (IgG, an indicator of extravasation), which is not found in the parenchyma in normal brain tissue, was apparently shown in CA1 parenchyma from 2 days after the ischemia, but IgG leakage was dramatically attenuated in the CA1 parenchyma treated with the extract and decursin. Furthermore, astrocyte endfeet, which are a component of the blood-brain barrier (BBB), were severely damaged at 5 days after the ischemia; however, post-treatment with the extract and decursin dramatically attenuated the damage of the endfeet. In brief, therapeutic treatment of the extract of Angelica gigas Nakai root and decursin after 5 min transient forebrain ischemia protected hippocampal neurons from the ischemia, showing that ischemia-induced BBB leakage and damage of astrocyte endfeet was significantly attenuated by the extract and decursin. Based on these findings, we suggest that Angelica gigas Nakai root containing decursin can be employed as a pharmaceutical composition to develop a therapeutic strategy for brain ischemic injury.


Assuntos
Angelica/química , Astrócitos/patologia , Benzopiranos/uso terapêutico , Barreira Hematoencefálica/patologia , Butiratos/uso terapêutico , Ataque Isquêmico Transitório/patologia , Extratos Vegetais/uso terapêutico , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Benzopiranos/química , Benzopiranos/farmacologia , Barreira Hematoencefálica/efeitos dos fármacos , Butiratos/química , Butiratos/farmacologia , Gerbillinae , Proteína Glial Fibrilar Ácida/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Imunoglobulina G/metabolismo , Masculino , Neuraminidase/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/farmacologia , Padrões de Referência , Memória Espacial/efeitos dos fármacos
11.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537826

RESUMO

Altered expression levels of N­methyl­D­aspartate receptor (NMDAR), a ligand­gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI­induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post­tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post­tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI­induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.


Assuntos
Isquemia Encefálica/metabolismo , Regulação da Expressão Gênica , Hipocampo/metabolismo , Hipertermia Induzida , Transtornos da Memória/metabolismo , Prosencéfalo/metabolismo , Receptores de N-Metil-D-Aspartato/biossíntese , Animais , Isquemia Encefálica/patologia , Morte Celular , Gerbillinae , Hipocampo/patologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/patologia , Neurônios , Prosencéfalo/patologia
12.
Int J Mol Sci ; 22(3)2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33498705

RESUMO

It has been reported that CD200 (Cluster of Differentiation 200), expressed in neurons, regulates microglial activation in the central nervous system, and a decrease in CD200 expression causes an increase in microglial activation and neuronal loss. The aim of this study was to investigate time-dependent changes in CD200 expression in the hippocampus proper (CA1, 2, and 3 fields) after transient forebrain ischemia for 5 min in gerbils. In this study, 5-min ischemia evoked neuronal death (loss) of pyramidal neurons in the CA1 field, but not in the CA2/3 fields, at 5 days postischemia. In the sham group, CD200 expression was found in pyramidal neurons of the CA1 field, and the immunoreactivity in the group with ischemia was decreased at 6 h postischemia, dramatically increased at 12 h postischemia, decreased (to level found at 6 h postischemia) at 1 and 2 days postischemia, and significantly increased again at 5 days postischemia. At 5 days postischemia, CD200 immunoreactivity was strongly expressed in microglia and GABAergic neurons. However, in the CA3 field, the change in CD200 immunoreactivity in pyramidal neurons was markedly weaker than that in the CA1 field, showing there was no expression of CD 200 in microglia and GABAergic neurons. In addition, treatment of 10 mg/kg risperidone (an atypical antipsychotic drug) after the ischemia hardly changed CD200 immunoreactivity in the CA1 field, showing that CA1 pyramidal neurons were protected from the ischemic injury. These results indicate that the transient ischemia-induced change in CD200 expression may be associated with specific and selective neuronal death in the hippocampal CA1 field following transient forebrain ischemia.


Assuntos
Antígenos CD/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Ataque Isquêmico Transitório/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Risperidona/farmacologia , Animais , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Gerbillinae , Ataque Isquêmico Transitório/patologia , Masculino , Microglia/patologia , Prosencéfalo/irrigação sanguínea , Prosencéfalo/patologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/patologia
13.
Exp Ther Med ; 21(3): 183, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33488792

RESUMO

Erigeron annuus (L.) PERS. (EALP) and Clematis mandshurica RUPR. (CMR) have been used in traditional remedies due to their medicinal effects. Recently, we reported that pretreatment with 200 mg/kg of YES-10® (a combination of extracts from leaves of EALP and CMR) displayed neuroprotective effects against brain ischemia and reperfusion injury. The present study analyzed the major ingredients of YES-10® and investigated whether neuroprotection from YES-10® was dependent upon antioxidant effects in the cornu ammonis 1 (CA1) field in the gerbil hippocampus, after transient forebrain ischemia for 5 min. YES-10® was demonstrated to predominantly contain scutellarin and chlorogenic acid. Pretreatment with YES-10® significantly increased protein levels and the immunoreactivity of copper/zinc-superoxide dismutase (SOD1) and manganese-superoxide dismutase (SOD2) was in the pyramidal neurons of the hippocampal CA1 field when these were examined prior to transient ischemia induction. The increased SODs in CA1 pyramidal neurons following YES-10® treatment were maintained after ischemic injury. In this case, the CA1 pyramidal neurons were protected from ischemia-reperfusion injury. Oxidative stress was significantly attenuated in the CA1 pyramidal neurons, and this was determined by 4-hydroxy-2-nonenal immunohistochemistry and dihydroethidium histofluorescence staining. Taken together, the results indicated that YES-10® significantly attenuated transient ischemia-induced oxidative stress and may be utilized for developing a protective agent against ischemic insults.

14.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33440708

RESUMO

Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood-brain barrier, which triggers gliosis after ischemic insults.


Assuntos
Calbindina 1/genética , Jejum , Expressão Gênica , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Animais , Calbindina 1/imunologia , Morte Celular/genética , Morte Celular/imunologia , Gerbillinae , Gliose/etiologia , Imunoglobulina G/imunologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia
15.
Cells ; 10(1)2021 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-33401719

RESUMO

Autonomic dysfunction in the central nervous system (CNS) can cause death after recovery from a cardiac arrest (CA). However, few studies on histopathological changes in animal models of CA have been reported. In this study, we investigated the prevalence of neuronal death and damage in various brain regions and the spinal cord at early times after asphyxial CA and we studied the relationship between the mortality rate and neuronal damage following hypothermic treatment after CA. Rats were subjected to 7-8 min of asphyxial CA, followed by resuscitation and prompt hypothermic treatment. Eight regions related to autonomic control (the cingulate cortex, hippocampus, thalamus, hypothalamus, myelencephalon, and spinal cord) were examined using cresyl violet (a marker for Nissl substance) and Fluoro-Jade B (a marker for neuronal death). The survival rate was 44.5% 1 day post-CA, 18.2% 2 days post-CA and 0% 5 days post-CA. Neuronal death started 12 h post-CA in the gigantocellular reticular nucleus and caudoventrolateral reticular nucleus in the myelencephalon and lamina VII in the cervical, thoracic, lumbar, and sacral spinal cord, of which neurons are related to autonomic lower motor neurons. In these regions, Iba-1 immunoreactivity indicating microglial activation (microgliosis) was gradually increased with time after CA. Prompt hypothermic treatment increased the survival rate at 5 days after CA with an attenuation of neuronal damages and death in the damaged regions. However, the survival rate was 0% at 12 days after CA. Taken together, our study suggests that the early damage and death of neurons related to autonomic lower motor neurons was significantly related to the high mortality rate after CA and that prompt hypothermic therapy could increase the survival rate temporarily after CA, but could not ultimately save the animal.


Assuntos
Sistema Nervoso Autônomo/patologia , Sistema Nervoso Central/patologia , Parada Cardíaca/patologia , Hipotermia Induzida , Neurônios/patologia , Animais , Antígenos Nucleares/metabolismo , Morte Celular , Masculino , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Ratos Sprague-Dawley , Análise de Sobrevida , Fatores de Tempo
16.
Nano Converg ; 7(1): 40, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351161

RESUMO

Dopamine is a key neurotransmitter that plays essential roles in the central nervous system, including motor control, motivation, arousal, and reward. Thus, abnormal levels of dopamine directly cause several neurological diseases, including depressive disorders, addiction, and Parkinson's disease (PD). To develop a new technology to treat such diseases and disorders, especially PD, which is currently incurable, dopamine release from living cells intended for transplantation or drug screening must be precisely monitored and assessed. Owing to the advantages of miniaturisation and rapid detection, numerous electrical techniques have been reported, mostly in combination with various nanomaterials possessing specific nanoscale geometries. This review highlights recent advances in electrical biosensors for dopamine detection, with a particular focus on the use of various nanomaterials (e.g., carbon-based materials, hybrid gold nanostructures, metal oxides, and conductive polymers) on electrode surfaces to improve both sensor performance and biocompatibility. We conclude that this review will accelerate the development of electrical biosensors intended for the precise detection of metabolite release from living cells, which will ultimately lead to advances in therapeutic materials and techniques to cure various neurodegenerative disorders.

17.
Molecules ; 25(19)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036412

RESUMO

Aronia melanocarpa, a black chokeberry, contains high levels of phenolic acids and polyphenolic flavonoids and displays antioxidative and anti-inflammatory effects. Through high-performance liquid chromatography for extracts from Aronia melanocarpa, we discovered that the extract contained chlorogenic acid and rutin as major ingredients. In this study, we examined the protective effects of the extract against ultraviolet B- (UVB)-induced photodamage in the dorsal skin of institute of cancer research (ICR) mice. Their dorsal skin was exposed to UVB, thereafter; the extract was topically applied once a day for seven days. Photoprotective properties of the extract in the dorsal skin were investigated by clinical skin severity score for skin injury, hematoxylin and eosin staining for histopathology, Masson's trichrome staining for collagens. In addition, we examined change in collagen type I and III, and matrix metalloproteinase (MMP)-1 and MMP-3 by immunohistochemistry. In the UVB-exposed mice treated with the extract, UVB-induced epidermal damage was significantly ameliorated, showing that epidermal thickness was moderated. In these mice, immunoreactivities of collagen type I and III were significantly increased, whereas immunoreactivities of MMP-1 and 3 were significantly decreased compared with those in the UVB-exposed mice. These results indicate that treatment with Aronia melanocarpa extract attenuates UV-induced photodamage by attenuating UVB-induced collagen disruption: these findings might be a result of the chlorogenic acid and rutin contained in the extract. Based on the current results, we suggest that Aronia melanocarpa can be a useful material for developing photoprotective adjuvant.


Assuntos
Ácido Clorogênico/química , Colágeno/metabolismo , Photinia/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Rutina/química , Raios Ultravioleta/efeitos adversos , Administração Tópica , Animais , Masculino , Metaloproteinases da Matriz/metabolismo , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação
18.
Lab Anim Res ; 36: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32832423

RESUMO

Obesity has been known as an independent risk factor for stroke. Effects of high-fat diet (HFD)-induced obesity on neuronal damage in the somatosensory cortex of animal models of cerebral ischemia have not been studied yet. In this study, HFD-induced obesity was used to study the impact of obesity on neuronal damage/loss and microgliosis in the somatosensory cortex of a gerbil model of 5-min transient forebrain ischemia. We used gerbils fed normal diet (ND) and HFD and chronologically examined microgliosis (microglial cell activation) by ionized calcium-binding adapter molecule 1 (Iba-1) immunohistochemistry. In addition, we examined neuronal damage or death by using neuronal nuclear protein (NeuN, a neuronal marker) immunohistochemistry and Fluoro-Jade B (F-J B, a marker for neuronal degeneration) histofluorescence staining. We found that ischemia-induced microgliosis in ND-fed gerbils was increased from 2 days post-ischemia; however, ischemia-mediated microgliosis in HFD-fed gerbils increased from 1 day post-ischemia and more accelerated with time than that in the ND-fed gerbils. Ischemia-induced neuronal death/loss in the somatosensory cortex in the ND-fed gerbils was apparently found at 5 days post-ischemia. However, in the HFD-fed gerbils, neuronal death/loss was shown from 2 days post-ischemia and progressively exacerbated at 5 days post-ischemia. Our findings indicate that HFD can evoke earlier microgliosis and more detrimental neuronal death/loss in the somatosensory cortex after transient ischemia than ND evokes.

19.
Molecules ; 25(16)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823713

RESUMO

This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1ß in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.


Assuntos
Angelica/química , Benzopiranos/farmacologia , Butiratos/farmacologia , Citocinas/metabolismo , Cabelo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Pele/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proteína HMGB1/metabolismo , Cabelo/crescimento & desenvolvimento , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pele/citologia , Pele/metabolismo
20.
Molecules ; 25(16)2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32781658

RESUMO

Chlorogenic acid (CGA), an ester of caffeic acid and quinic acid, is among the phenolic acid compounds which can be naturally found in green coffee extract and tea. CGA has been studied since it displays significant pharmacological properties. The aim of this study was to investigate the effects of CGA on cognitive function and neuroprotection including its mechanisms in the hippocampus following transient forebrain ischemia in gerbils. Memory and learning following the ischemia was investigated by eight-arm radial maze and passive avoidance tests. Neuroprotection was examined by immunohistochemistry for neuronal nuclei-specific protein and Fluoro-Jade B histofluorescence staining. For mechanisms of the neuroprotection, alterations in copper, zinc-superoxide dismutase (SOD1), SOD2 as antioxidant enzymes, dihydroethidium and 4-hydroxy-2-nonenal as indicators for oxidative stress, and anti-inflammatory cytokines (interleukin (IL)-4 and IL-13) and pro-inflammatory cytokines (tumor necrosis factor α (TNF-α) and IL-2) were examined by Western blotting and/or immunohistochemistry. As a result, pretreatment with 30 mg/kg CGA attenuated cognitive impairment and displayed a neuroprotective effect against transient forebrain ischemia (TFI). In Western blotting, the expression levels of SOD2 and IL-4 were increased due to pretreatment with CGA and, furthermore, 4-HNE production and IL-4 expressions were inhibited by CGA pretreatment. Additionally, pretreated CGA enhanced antioxidant enzymes and anti-inflammatory cytokines and, in contrast, attenuated oxidative stress and pro-inflammatory cytokine expression. Based on these results, we suggest that CGA can be a useful neuroprotective material against ischemia-reperfusion injury due to its antioxidant and anti-inflammatory efficacies.


Assuntos
Ácido Clorogênico/farmacologia , Cognição/efeitos dos fármacos , Hipocampo/patologia , Isquemia/patologia , Isquemia/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Aldeídos/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Hipocampo/efeitos dos fármacos , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Isquemia/metabolismo , Camundongos , Fármacos Neuroprotetores/farmacologia , Superóxido Dismutase/metabolismo
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