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1.
目的探讨大鼠局灶性脑缺血后磷酸化Rb蛋白(p-Rb,ser 795)的表达定位与神经元凋亡的时空关系。方法制备大鼠大脑中动脉梗塞(MCAO)模型,分为假手术对照组、缺血1h再灌注12h,1d,3d,7d组。利用TUNEL法检测缺血周边区细胞凋亡情况;TUNEL与p-Rb荧光双标观察神经元凋亡与p-Rb表达、定位的关系。结果缺血半暗带内大部分TUNEL阳性细胞为神经元;大鼠MCAO再灌注12h和1d,TUNEL与p-Rb分别以重叠和镶嵌的方式共定位;再灌注3d,7d发生p-Rb核浆转移的神经元与TUNEL染色细胞仍然分别维持在高水平,但是两者却没有明显的共定位关系。结论 p-Rb可能参与短暂局灶脑缺血后神经元早期凋亡过程,间接或者不参与神经元晚期凋亡过程。 相似文献
2.
The aim of this study was to investigate the relationship between cell cycle reentry and apoptosis in cultured cortical neurons
following oxygen–glucose deprivation (OGD). We found that the percentage of neurons with BrdU uptake, TUNEL staining, and
colocalized BrdU uptake and TUNEL staining was increased relative to control 6, 12 and 24 h after 1 h of OGD. The number of
neurons with colocalized BrdU and TUNEL staining was decreased relative to the number of TUNEL-positive neurons at 24 h. The
expression of phosphorylated retinoblastoma protein (phospho-Rb) was significantly increased 6, 12 and 24 h after OGD, parallel
with the changes in BrdU uptake. Phospho-Rb and TUNEL staining were colocalized in neurons 6 and 12 h after OGD. This colocalization
was strikingly decreased 24 h after OGD. Treatment with the cyclin-dependent kinase inhibitor roscovitine (100 μM) decreased
the expression of phospho-Rb and reduced neuronal apoptosis in vitro. These results demonstrated that attempted cell cycle
reentry with phosphorylation of Rb induce early apoptosis in neurons after OGD and there must be other mechanisms involved
in the later stages of neuronal apoptosis besides cell cycle reentry. Phosphoralated Rb may be an important factor which closely
associates aberrant cell cycle reentry with the early stages of neuronal apoptosis following ischemia/hypoxia in vitro, and
pharmacological interventions for neuroprotection may be useful directed at this keypoint. 相似文献
3.
To study whether recombinant human erythropoietin (rhEPO) reduces neuronal apoptosis through inhibiting over-expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in nucleus induced by brain ischemia/reperfusion in rats, 48 adult Sprague-Dawley rats were randomly divided into 3 groups: sham, saline and EPO groups. Animal models of brain ischemia/reperfusion were established by middle cerebral artery occlusion in rats. The effects of EPO on the sizes of ischemia tissue were observed by TTC staining. The over-expression of GAPDH in nucleus was detected by Hoechst-33258 and anti-GAPDH antibody double staining. The neuronal apoptosis in penumbral was detected by Nissl's staining and Hoechst-33258 immunofluorescence, respectively. The results showed that rhEPO treatment (3 000 U/kg, three times daily, i.p.) apparently reduced the sizes of infarct brain tissue in ischemia/reperfusion rats. rhEPO inhibited over-expression of GAPDH in nucleus of apoptotic neurons. In the meantime rhEPO decreased the number of apoptotic neurons in ischemia/reperfusion rats. These results suggest that rhEPO may induced reduction of neuronal apoptosis in penumbra may be through inhibiting over-expression of GAPDH in nucleus of apoptotic neurons induced by ischemia/reperfusion. Reduction of GAPDH over-expression in nucleus may play a pivotal role in EPO inhibiting neuronal apoptosis in cerebral ischemia/reperfusion rats, providing experimental evidence for EPO neuro-protecting effects against ischemia/reperfusion. 相似文献
4.
Cell-cycle regulators are involved in transient cerebral ischemia induced neuronal apoptosis in female rats 总被引:10,自引:0,他引:10
Recent evidence indicates that cell-cycle regulating proteins are involved in apoptotic process in post-mitotic neurons. In this study, we examined cell-cycle regulators for G1/S cell-cycle progression after a transient focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. In the cerebral frontoparietal cortex, we observed a marked induction of Cyclin D1 (a coactivator of Cdks), and proliferating cell nuclear antigen (PCNA), together with upregulated Cdk kinase activities. This process is accompanied with multiple phosphorylation of retinoblastoma (Rb) protein at Cdk phosphorylation sites in neurons from the ischemic cortex. We further examined DNA synthesis by the incorporation of BrdU, a nucleotide analog that incorporates into newly synthesized DNA. Within 24-h of reperfusion after 60-min occlusion, substantial BrdU-positive neurons were observed in the ischemic cortex. Inhibition of Cdk4 activity during this ischemia/reperfusion is highly neuroprotective. These results suggest that ischemia/reperfusion cerebral damage induces signalings at the G1/S cell-cycle transition, and may constitute a critical step in the neuronal apoptotic pathway in ischemia/reperfusion induced neuronal damage. 相似文献
5.
Histochemical characterization of NADPH diaphorase positive neuronal pools in the rabbit lumbosacral segments was performed during and after transient spinal cord ischemia. Strongly enhanced staining of NADPH diaphorase positive structures appeared in the superficial dorsal horn, the pericentral region and in the neurons of the sacral parasympathetic nucleus at the end of 40 min of abdominal aorta ligation or after 1 day reperfusion. Four days after ischemia, NADPH-d positive neurons and vessels were detected in the central gray matter despite well developed necrosis in this location. Regional nitric oxide synthesis and its vasodilatatory effect during the period of aortic occlusion may account for the observed selective resistance of these spinal cord neurons to transient ischemia. 相似文献
6.
Jung Hoon Choi Ki-Yeon Yoo Ok Kyu Park Choong Hyun Lee Sung Koo Kim In Koo Hwang Yun Lyul Lee Hyung-Cheul Shin Moo-Ho Won 《Cellular and molecular neurobiology》2010,30(6):929-938
Neurogenesis occurs during the embryonic stage and throughout life. Brain injuries such as ischemic insults enhance cell proliferation
in some areas of the brain. We examined proliferation of newly generated cells in each layer of the gerbil main olfactory
bulb (MOB) after 5 min of transient cerebral ischemia using bromodeoxyuridine (BrdU) immunohistochemistry. Ischemia-related
neuronal death in the MOB was not detected using Fluoro-Jade B histofluorescence and TUNEL staining. Many BrdU-positive (+) cells were found in the rostral migratory stream in control and ischemic MOBs. Significant increase of BrdU+ cells was observed in the granule cell layer (GCL) and glomerular layer (GL) from 15 days post-ischemia, and BrdU+ cells were very much higher than those of the control group 30 days post-ischemia. At this time point after ischemia/reperfusion,
a few BrdU+ cells in the GL and GCL were co-localized with calretinin+ cells, and many BrdU+ cells expressed doublecortin, a marker of immature neurons. These results indicate that cell proliferation is increased in
the GCL and GL without apparent neuronal loss from 15 days after transient cerebral ischemia in gerbils. 相似文献
7.
Hiroto Uchida Yuki Fujita Misato Matsueda Masahiro Umeda Shunsuke Matsuda Hiroyuki Kato Jiro Kasahara Tsutomu Araki 《Cellular and molecular neurobiology》2010,30(7):1125-1134
Focal brain lesions such as transient focal cerebral ischemia can lead to neuronal damage in remote areas, including the ipsilateral
substantia nigra and hippocampus, as well as in the ischemic core. In this study, we investigated acute changes in the ipsilateral
hippocampus from 1 up to 7 days after 90 min of transient focal cerebral ischemia in rats, using anti-NeuN (neuronal nuclei),
anti-Cu/Zn-superoxide dismutase (Cu/Zn-SOD), anti-Mn-SOD, anti-neuronal nitric oxide synthase (nNOS), anti-inducible NOS (iNOS),
anti-glial fibrillary acidic protein (GFAP), anti-ionized calcium-binding adaptor molecule 1(Iba 1) and anti-2′,3′-cyclic
nucleotide 3′-phosphodiesterase (CNPase) antibodies. In our western blot and histochemical analyses, present results show
that transient focal cerebral ischemia in rats can cause a severe and acute damage of neurons and oligodendrocytes in the
ipsilateral hippocampal CA1 sector. The present findings also demonstrate that the expression of iNOS produced by Iba 1-immunopositive
microglia precedes the damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal
cerebral ischemia. In contrast, our results suggest that increased reactive oxygen species (ROS) production during reperfusion
cannot lead to damage of neurons and oligodendrocytes in the ipsilateral hippocampal CA1 sector after transient focal cerebral
ischemia, because of an insufficient expression of Cu/Zn-SOD and Mn-SOD. Our double-labeled immunohistochemical study demonstrates
that the overexpression of iNOS produced by Iba 1-immunopositive microglia may play a pivotal role in the damage of neurons
and oligodendrocytes in the ipsilateral hippocampal CA1 sector at an acute stage after transient focal cerebral ischemia. 相似文献
8.
Chan Woo Park Jae-Chul Lee Ji Hyeon Ahn Dae Hwan Lee Geum-Sil Cho Bing Chun Yan Joon Ha Park In Hye Kim Hui Young Lee Moo-Ho Won Jun Hwi Cho 《Cellular and molecular neurobiology》2013,33(7):991-1001
The extent of neuronal damage/death in some brain regions is highly correlated to duration time of transient ischemia. In the present study, we carried out neuronal degeneration/death and glial changes in the septum 4 days after 5, 10, 15, and 20 min of transient cerebral ischemia using gerbils. To examine neuronal damage, Fluoro-Jade B (F-J B, a marker for neuronal degeneration) histofluorescence staining was used. F-J B positive (+) cells were detected in the septo-hippocampal nucleus (SHN) of the septum only in the 20 min ischemia-group; the mean number of F-J B+ neurons was 14.9 ± 2.5/400 μm2 in a section. Gliosis of astrocytes and microglia was examined using anti-glial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding adapter molecule 1 (Iba-1), respectively. In all the ischemia-groups, GFAP- and Iba-1-immunoreactive astrocytes and microglia, respectively, were increased in number, and apparently tended to be increased in their immunoreactivity. Especially, in the 20 min ischemia-group, the number and immunoreactivity of Iba-immunoreactive microglia was highest and strongest in the ischemic SHN 4 days after ischemia–reperfusion. In brief, our findings showed that neuronal damage/death in the SHN occurred and gliosis was apparently increased in the 20 min ischemia-group at 4 days after ischemia–reperfusion. 相似文献
9.
Shibani S. Mukerji Riley N. Rainey Jamie L. Rhodes Alison K. Hall 《Journal of neurochemistry》2009,111(5):1138-1148
Focal cerebral ischemia and reperfusion initiates complex cellular and molecular interactions that lead to either cell repair or destruction. In earlier work, we found that activin A is an early gene response to cerebral ischemia and supports cortical neuron survival in vitro. In this study, the ability of exogenous activin A to attenuate injury from transient middle cerebral artery occlusion was tested in adult mice. Intracerebroventricular administration of activin A prior to middle cerebral artery occlusion reduced infarct volume apparent 1 day after experimental stroke. A single activin A administration at 6 h following ischemia/reperfusion reduced lesion volumes at 1 and 3 days and led to improved neurobehavior. Moreover, activin A treatment spared neurons within the ischemic hemisphere and led to a concomitant reduction in microglial activation. Activation of the stress-responsive kinases p38 and c- jun N-terminal kinase implicated in neuronal apoptosis after stroke was reduced following activin A treatment. Together these findings suggest that activin A promotes tissue survival after focal cerebral ischemia/reperfusion with an extended therapeutic window. 相似文献
10.
目的探讨细胞周期对于大鼠局灶性脑缺血后神经元的影响。方法采用MCAO方法制作大鼠局灶性脑缺血模型,应用免疫荧光技术观察缺血后1d、3d、7d、14d大鼠缺血侧病灶周围神经元中磷酸化细胞周期蛋白CDK2、CDC2及磷酸化Rb的表达。结果与正常对照组相比,缺血后1d、3d组磷酸化CDK2和磷酸化Rb的表达量明显增加(P〈0.05)。缺血后7d、14d组磷酸化CDK2和磷酸化Rb的表达量无增加。磷酸化CDC2在正常组及缺血组均无明显表达。结论大鼠局灶性脑缺血后早期部分神经元再次进入细胞周期,提示细胞周期调控参与了大鼠局灶性脑缺血后神经元的凋亡。 相似文献
11.
《Phytomedicine》2021
BackgroundOxidative stress and frequently unwanted alterations in mitochondrial structure and function are key aspects of the pathological cascade in transient focal cerebral ischemia. Chikusetsu saponin V (CHS V), a major component of saponins from Panax japonicas, can attenuate H2O2-induced oxidative stress in SH-SY5Y cells.PurposeThe aim of the present study was to investigate the neuroprotective effects and the possible underlying mechanism of CHS V on transient focal cerebral ischemia/reperfusion.MethodsMice with middle cerebral artery occlusion (MCAO) and cultured cortical neurons exposed to oxygen glucose deprivation (OGD) were used as in vivo and in vitro models of cerebral ischemia, respectively. The neurobehavioral scores, infarction volumes, H&E staining and some antioxidant levels in the brain were evaluated. The occurrence of neuronal death was estimated. Total and mitochondrial reactive oxygen species (ROS) levels, as well as mitochondrial potential were measured using flow cytometry analysis. Mitochondrial structure and respiratory activity were also examined. Protein levels were investigated by western blotting and immunohistochemistry.ResultsCHS V effectively attenuated cerebral ischemia/reperfusion (CI/R) injury, including improving neurological deficits, shrinking infarct volume and reducing the number of apoptotic cells. Furthermore, CHS V treatment remarkably increased antioxidant levels and reduced ROS levels and mitochondrial damage by enhancing the expression and deacetylation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) by activating AMPK and SIRT-1, respectively.ConclusionOur data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1α with AMPK and SIRT-1. 相似文献
12.
Yoo DY Kim W Nam SM Chung JY Choi JH Yoon YS Won MH Hwang IK 《Neurochemical research》2012,37(5):1011-1018
In a previous study, we reported that the administration of pyridoxine (vitamin B6) to mice for 3 weeks significantly increased cell proliferation and neuroblast differentiation in the dentate gyrus without
any neuronal damage. In the present study, we investigated the restorative potentials of pyridoxine on ischemic damage in
the hippocampal CA1 region of Mongolian gerbils. Gerbils were subjected to 5 min of transient ischemia, and surgical operation
success was assessed by ophthalmoscope during occlusion of common carotid arteries and spontaneous motor activity at 1 day
after ischemia/reperfusion. Pyridoxine (350 mg/kg) or its vehicle (physiological saline) was intraperineally administered
to ischemic gerbils twice a day starting 4 days after ischemia/reperfusion for 30 or 60 days. The repeated administration
of pyridoxine for 30 and 60 days significantly increased doublecortin-immunoreactive neuroblasts in the dentate gyrus and
increased NeuN-immunoreactive mature neurons and βIII-tubulin-immunoreactive dendrites in the hippocampal CA1 region. Furthermore,
brain-derived neurotrophic factor (BDNF) protein levels were significantly increased in pyridoxine-treated groups compared
to those in the vehicle-treated groups. These results suggest that chronic administration of pyridoxine enhances neuroblast
differentiation in the dentate gyrus and induces new mature neurons in the hippocampal CA1 region by up-regulating BDNF expression
in hippocampal homogenates. 相似文献
13.
Yoo KY Yoo DY Hwang IK Park JH Lee CH Choi JH Kwon SH Her S Lee YL Won MH 《Neurochemical research》2011,36(12):2417-2426
Innate immune system is very important to modulate the host defense against a large variety of pathogens. Toll-like receptors
(TLRs) play a key role in controlling innate immune response. Among TLRs, TLR4 is a specific receptor for lipopolysaccharide
and associated with the release of pro-inflammatory cytokines. In the present study, we investigated ischemia-related changes
of TLR4 immunoreactivity and its protein level, and nuclear factor κB (NF-κB) p65 immunoreactivity regarding inflammatory
responses in the hippocampal CA1 region after 5 min of transient cerebral ischemia to identify the correlation between transient
ischemia and inflammation. In the sham-operated group, TLR4 immunoreactivity was easily detected in pyramidal neurons of the
hippocampal CA1 region (CA1). TLR4 immunoreactivity in pyramidal neurons was distinctively decreased after ischemia/reperfusion
(I/R); instead, based on double immunofluorescence study, TLR4 immunoreactivity was expressed in non-pyramidal neurons and
astrocytes from 2 days postischemia. In addition, TLR4 protein level was lowest at 1 day postischemia and highest 4 days after
I/R. On the other hand, NF-κB p65 immunoreactivity was not detected in the CA1 of the sham-operated group, and NF-κB p65 immunoreactivity
was not observed until 1 day after I/R. However, NF-κB p65 immunoreactivity began to be expressed in astrocytes at 2 days
postischemia, and the immunoreactivity was strong 4 days postischemia. Our results indicate that TLR4 and NF-κB p65 immunoreactivity
are changed in CA1 pyramidal neurons and newly expressed in astrocytes, not in microglia, in the CA1 region after transient
cerebral ischemia. 相似文献
14.
The effects of a selective inducible nitric oxide synthase inhibitor aminoguanidine (AG) on neuronal cells survival in hippocampal
CA1 region after middle cerebral artery occlusion (MCAO) were examined. Transient focal cerebral ischemia was induced in rats
by 60 or 90 min of MCAO, followed by 7 days of reperfusion. AG treatment (150 mg/kg i.p.) significantly reduced total infarct
volumes: by 70% after 90 min MCAO and by 95% after 60 min MCAO, compared with saline-treated ischemic group. The number of
degenerating neurons in hippocampal CA1 region was also markedly lower in aminoguanidine-treated ischemic groups compared
to ischemic groups without AG-treatment. The number of iNOS-positive cells significantly increased in the hippocampal CA1
region of ischemic animals, whereas it was reduced in AG-treated rats. Our findings demonstrate that aminoguanidine decreases
ischemic brain damage and improves neurological recovery after transient focal ischemia induced by MCAO. 相似文献
15.
Schreiberová A Kisucká A Hricová L Kucharíková A Pavel J Lukáčová N 《Journal of molecular histology》2012,43(2):203-213
Spinal cord ischemia belongs to serious and relatively frequent diseases of CNS. The aim of the present study was to find
out the vulnerability of nitrergic neurons to 15 min transient spinal cord ischemia followed by 1 and 2 weeks of reperfusion.
We studied neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in structural
elements of lumbosacral spinal cord along its rostrocaudal axis. In addition, a neurological deficit of experimental animals
was evaluated. Spinal cord ischemia, performed on the rabbit, was induced by abdominal aorta occlusion using Fogarty catheter
introduced into the right femoral artery for a period of 15 min. After surgical intervention the animals survived for 7 and
14 days. nNOS-immunoreactivity (nNOS-IR) was measured by immunohistochemical and NADPHd-positivity by histochemical method,
and both immunohistochemical and histochemical stainings were quantified by densitometric analyses. Neurological deficit was
evaluated according Zivin′s criteria. The number of nNOS-IR and/or NADPH-d positive neurons and the density of neuropil were
markedly increased in superficial dorsal horn (laminae I–III) after 15 min ischemia and 7 days of reperfusion. However, ischemia
followed by longer time of survival (14 days) returned the number of nNOS-IR and NADPH-d positive neurons to control. In the
pericentral region (lamina X) containing interneurons and crossing fibers of spinal tracts, than in lamina VII and in dorsomedial
part of the ventral horn (lamina VIII) we recorded a decreased number of nNOS-IR and NADPH-d positive neurons after both ischemia/reperfusion
periods. In the medial portion of lamina VII and dorsomedial part of the ventral horn (lamina VIII) we observed many necrotic
loci. This area was the most sensitive to ischemia/reperfusion injury. Fifteen minute ischemia caused a marked deterioration
of neurological function of hind limbs, often developing into paraplegia. A quantitative immunohistochemical and histochemical
study have shown a strong vulnerability of nitrergic neurons in intermediate zone to transient spinal cord ischemia. 相似文献
16.
Suzuki Y Yamazaki Y Hozumi Y Okada M Tanaka T Iseki K Ohta N Aoyagi M Fujii S Goto K 《Histochemistry and cell biology》2012,137(4):499-511
Diacylglycerol kinase (DGK) plays a key role in pathophysiological cellular responses by regulating the levels of a lipid
messenger diacylglycerol. Of DGK isozymes, DGKζ localizes to the nucleus in various cells such as neurons. We previously reported
that DGKζ translocates from the nucleus to the cytoplasm in hippocampal CA1 pyramidal neurons after 20 min of transient forebrain
ischemia. In this study, we examined the underlying mechanism of DGKζ translocation using hippocampal slices exposed to oxygen-glucose
deprivation (OGD) to simulate an ischemic model of the brain. DGKζ-immunoreactivity gradually changed from the nucleus to
the cytoplasm in CA1 pyramidal neurons after 20 min of OGD and was never detected in the nucleus after reoxygenation. Intriguingly,
DGKζ was detected in the nucleus at 10 min OGD whereas the following 60 min reoxygenation induced complete cytoplasmic translocation
of DGKζ. Morphometric analysis revealed that DGKζ cytoplasmic translocation correlated with nuclear shrinkage indicative of
an early process of neuronal degeneration. The translocation under OGD conditions was blocked by NMDA receptor (NMDAR) inhibitor,
and was induced by activation of NMDAR. Chelation of the extracellular Ca2+ blocked the translocation under OGD conditions. These results show that DGKζ cytoplasmic translocation is triggered by activation
of NMDAR with subsequent extracellular Ca2+ influx. Furthermore, inhibition of PKC activity under OGD conditions led to nuclear retention of DGKζ in about one-third
of the neurons, suggesting that PKC activity partially regulates DGKζ cytoplasmic translocation. These findings provide clues
to guide further investigation of glutamate excitotoxicity mechanisms in hippocampal neurons. 相似文献
17.
Hui-Xia Geng Rui-Ping Li Ying-Ge Li Xiao-Qing Wang Li Zhang Jin-Bo Deng Lai Wang Jie-Xin Deng 《Neurochemical research》2017,42(10):2841-2849
Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an important pathological process in cerebral ischemia–reperfusion injury. 14,15-EET, an intermediate metabolite of arachidonic acid, can promote cell survival during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway is involved this survival mechanism is not fully understood. In this study, we observed that infarct size in ischemia–reperfusion injury was reduced in sEH gene knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment reduced neuronal apoptosis in the oxygen–glucose deprivation and re-oxygenation group in vitro. The mitochondrial apoptosis pathway was also inhibited, as evidenced by AIF translocation from the mitochondria to nucleus and the reduction in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15-EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2 (anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the reduction of neuronal apoptosis by EET. Our study suggests that 14,15-EET could suppress neuronal apoptosis and reduce infarct volume through the mitochondrial apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved in the neuroprotection against ischemia–reperfusion by 14,15-EET. 相似文献
18.
Atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in ischemic stroke 总被引:1,自引:0,他引:1
Hong H Zeng JS Kreulen DL Kaufman DI Chen AF 《American journal of physiology. Heart and circulatory physiology》2006,291(5):H2210-H2215
Statins have recently been shown to exert neuronal protection in ischemic stroke. Reactive oxygen species, specifically superoxide formed during the early phase of reperfusion, augment neuronal injury. NADPH oxidase is a key enzyme for superoxide production. The present study tested the hypothesis that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia. Transient focal ischemia was created in halothane-anesthetized adult male Sprague-Dawley rats (250-300 g) by middle cerebral artery occlusion (MCAO). Atorvastatin (Lipitor, 10 mg/kg sc) was administered three times before MCAO. Infarct volume was measured by triphenyltetrazolium chloride staining. NADPH oxidase enzymatic activity and superoxide levels were quantified in the ischemic core and penumbral regions by lucigenin (5 microM)-enhanced chemiluminescence. Expression of NADPH oxidase membrane subunit gp91(phox) and membrane-translocated subunit p47(phox) and small GTPase Rac-1 was analyzed by Western blot. NADPH oxidase activity and superoxide levels increased after reperfusion and peaked within 2 h of reperfusion in the penumbra, but not in the ischemic core, in MCAO rats. Atorvastatin pretreatment prevented these increases, blunted expression of membrane subunit gp91(phox), and prevented translocation of cytoplasmic subunit p47(phox) to the membrane in the penumbra 2 h after reperfusion. Consequently, cerebral infarct volume was significantly reduced in atorvastatin-treated compared with nontreated MCAO rats 24 h after reperfusion. These results indicate that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia. 相似文献
19.
Hualing Li Changqing Sun Yu Wang Yuxiao Gao Yichen Liu Yan Gao Xu Li Chenggang Zhang 《The journal of histochemistry and cytochemistry》2013,61(1):45-54
The present study aimed to evaluate the expression of neuro-oncological ventral antigen 1
(Nova1) in cerebral ischemia/reperfusion (I/R) insults by immunohistochemistry. The focal
cerebral I/R model was induced by right middle cerebral artery occlusion (MCAO) for 120
min followed by 1 day, 7 days, and 14 days of reperfusion in Sprague-Dawley (SD) rats. The
results showed that Nova1 was expressed in nearly the whole brain, although with higher
density in hippocampus, hypothalamus, cingulate cortex, and medial habenular nucleus. The
immunoreactivity of Nova1 neurons was increased dramatically, especially on both sides of
the hippocampal CA1 region, after 1 day of reperfusion. A strong response
occurred at the ipsilateral CA1 region between 1 day and 7 days of reperfusion.
Likewise, strong compensatory responses of Nova1 expression were observed on the
contralateral side of the striate cortex, dentate gyrus, and hypothalamus. Interestingly,
more Nova1 neurons were observed to translocate to the dendrites and growth cones of the
axons in the hypothalamus on the ischemic side after 7 days of reperfusion. In conclusion,
our data suggest that Nova1 might mediate neuronal responsiveness, and its expression
might positively correlate with neural repair after I/R insults in the rat brain. 相似文献
20.