Induction of 70-kDa Heat Shock Protein and hsp70 mRNA following Transient Focal Cerebral Ischemia in the Rat

Kinouchi, Hiroyuki; Sharp, Frank R.; Hill, Mary Pat; Koistinaho, Jari; Sagar, Stephen M.; Chan, Pak H.

doi:10.1038/jcbfm.1993.13

Cited by 185 publications

(85 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Prolonged cerebral ischemia up-regulates HSP70 in endothelial cells in normal rats and, to a reduced extent, IPC-treated rats, as shown in the current study and previous studies (Kinouchi et al, 1993a;Lindsberg et al, 1996). The current study does not address the question of whether such production of HSP70 by the vasculature is protective.…”

Section: T Masada Et Al 30contrasting

confidence: 59%

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

Masada

Hua

et al. 2001

J Cereb Blood Flow Metab

110

View full text Add to dashboard Cite

Summary: Ischemic preconditioning (IPC) induces neuroprotection to subsequent severe ischemia, but its effect on the cerebrovasculature has not been studied extensively. This study evaluated the effects of IPC on brain edema formation and endothelial cell damage that follows subsequent permanent focal cerebral ischemia in the rat. Transient (15 minute) middle cerebral artery occlusion (MCAO) was used for IPC. Three days after IPC or a sham operation, permanent MCAO was induced. Twenty-four hours after permanent MCAO, neurologic deficit, infarction volume, and water and ion content were evaluated. Six hours post-ischemia, blood-brain barrier (BBB) permeability was examined using [ 3 H]-inulin. Water, ion contents, and BBB permeability were assessed in three zones (core, intermediate, and outer) depending on their relation to the MCA territory. Heat shock protein 70 (HSP70) was also examined as a potential marker of vascular injury. The model of IPC significantly reduced brain infarction and neurologic deficit. Compared with a sham operation, IPC also significantly attenuated brain edema formation in the intermediate (sham and IPC water contents: 5.99 ± 0.65 vs. 4.99 ± 0.81 g/g dry weight; P < 0.01) and outer zones (5.02 ± 0.48 vs. 4.37 ± 0.42 g/g dry weight; P < 0.01) of the ipsilateral hemisphere but not in the core zone. Blood-brain barrier disruption assessed by [ 3 H]-inulin was significantly attenuated in the IPC group and the number of blood vessels that displayed HSP70 immunoreactivity was also reduced. Thus, IPC significantly attenuates ischemic brain edema formation, BBB disruption, and, as assessed by HSP70, vascular injury. Understanding the mechanisms involved in IPC may provide insight into methods for preserving cerebrovascular function during ischemia. Key Words: Brain ischemia-Ischemic preconditioning-Brain edema-Blood-brain barrier-HSP70.

show abstract

Section: T Masada Et Al 30contrasting

confidence: 59%

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

Masada

Hua

et al. 2001

J Cereb Blood Flow Metab

110

View full text Add to dashboard Cite

show abstract

“…Impaired expression of other genes such as heat shock protein in the infarcted area has also been noted by others [64]. Fos/Jun heterodimer functions as a transcription activator by a sequence-specific interaction with the consensus AP-1 sequence and stimulates the transcription of nearby promoters by a yet undefined mechanism.…”

Section: Discussionmentioning

confidence: 62%

“…It is possible that the capability to translate c-fos mRNA into Fos may be compromised in the severely ischemic cortex destined for degeneration. Alternatively, a limited diffusion of the antisense oligodeoxynucleotide to regions remote from the lateral ventricles might be partially responsible for the inconsistent effects on cortical Fos expression.Impaired expression of other genes such as heat shock protein in the infarcted area has also been noted by others [64]. Fos/Jun heterodimer functions as a transcription activator by a sequence-specific interaction with the consensus AP-1 sequence and stimulates the transcription of nearby promoters by a yet undefined mechanism.…”

mentioning

confidence: 62%

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Liu

Salminen

et al. 1994

Annals of Neurology

View full text Add to dashboard Cite

Activation of c-fos, an immediate early gene, and the subsequent expression of the Fos protein have been noted following focal cerebral ischemia. Fos and Jun form a heterodimer as activator protein 1 (AP-1), which transregulates the expression of several genes. To study the postischemic events related to c-fos expression, we suppressed the expression of c-fos by intraventricular infusion of an antisense Oligodeoxynucleotide (anti-rncfosr 115 ) of c-fos mRNA. The effectiveness of antirncfosr 115 was confirmed first by its capability to block in vitro c-fos mRNA translation. In vivo, after intraventricular infusion of 32 P-labeled anti-rncfosr 115 , the oligodeoxynucleotide was internalized within 6 hours and detectable also in the nucleic acids fraction up to 41 hours. Treatment of the recovered nucleic acids with RNase H separated the labeled Oligodeoxynucleotide from the nucleic acid fraction, indicating an association of the antisense Oligodeoxynucleotide and cellular RNA after uptake. When focal cerebral ischemia was induced 16 hours after the infusion of antirncfosr 115 , the postischemic increase in Fos expression and AP-1 binding activity were suppressed. Specificity of the effect of anti-rncfosr 115 was suggested by its failure to suppress the DNA binding activity of nuclear cyclic AMP response elements. These results support the hypothesis that increased AP-1 binding activity following focal cerebral ischemia is dependent on Fos expression and can be inhibited in vivo by antisense c-fos oligodeoxynucleotides.The molecular events of brain adaptation to injury that may underlie functional recovery after stroke remain largely undefined. Recent observations of altered gene expression in ischemic brain using animal stroke models have opened new avenues for exploration of the biochemical cascades after stroke [1][2][3][4][5][6][7][8][9][10][11]. These postischemic events include an increase in extracellular excitatory amino acid neurotransmitters such as glutamate. Glutamate receptor-mediated activation of phospholipases and protein kinases results in the alteration of nuclear regulatory processes, including the expression of immediate early genes such as c-fos, junB, and c-jun [5,12]. The Fos, Jun, and JunB proteins have been shown to form activator protein 1 (AP-1) through a conserved dimerization domain, i.e., the leucine zipper [13]. Transcription regulator AP-1 protein binds a specific DNA motif and is believed to transactivate the expression of a number of late effector genes [14][15][16][17][18][19]. In the ischemic brain, we have previously demonstrated an increase in AP-1 binding activity [9]. A number of genes that bear neurotrophic properties may be regulated by transcription regulator AP-1. These genes, such as heat shock protein [1,4,[19][20][21][22], amyloid [23], neurotrophins [7], and protein tyrosine kinase receptor trkB [24], have been shown to be induced following cerebral ischemia. The causal relationship between the Fos/Jun-AP-1 cascade and the subsequent expression of the late e...

show abstract

“…Some molecules may exhibit different expression pattern in different ischemic stroke model. For example, heat shock protein 70 was induced following the transient focal cerebral ischemia model,33, 34, 35 but was equally expressed in both peri‐infarct and healthy tissues in the permanent focal cerebral ischemia model36; sirtuin 1 expression was increased in neurons of the ipsilesional mouse brain in transient MCAO model,37 but was decreased in the ischemic hemisphere in the permanent MCAO model 38. To study a candidate for molecular therapeutic or imaging target in a variety of cerebral ischemic stroke may provide adequate information for its application.…”

Section: Discussionmentioning

confidence: 99%

Neuronal PirB Upregulated in Cerebral Ischemia Acts as an Attractive Theranostic Target for Ischemic Stroke

Wang

Zhang

Xia

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundIschemic stroke is a complex disease with multiple etiologies and clinical manifestations. Paired immunoglobulin‐like receptor B (PirB), which is originally thought to function exclusively in the immune system, is now also known to be expressed by neurons. A growing number of studies indicate that PirB can inhibit neurite outgrowth and restrict neuronal plasticity. The aim of the study is to investigate whether PirB can be an attractive theranostic target for ischemic stroke.Methods and ResultsFirst, we investigated the spatial‐temporal expression of PirB in multiple ischemic stroke models, including transient middle cerebral artery occlusion, photothrombotic cerebral cortex ischemia, and the neuronal oxygen glucose deprivation model. Then, anti‐PirB immunoliposome nanoprobe was developed by thin‐film hydration method and investigated its specific targeting in vitro and in vivo. Finally, soluble PirB ectodomain (sPirB) protein delivered by polyethylene glycol–modified nanoliposome was used as a therapeutic reagent for ischemic stroke by blocking PirB binding to its endogenous ligands. These results showed that PirB was significantly upregulated after cerebral ischemic injury in ischemic stroke models. Anti‐PirB immunoliposome nanoprobe was successfully developed and specifically bound to PirB in vitro. There was accumulation of anti‐PirB immunoliposome nanoprobe in the ischemic hemisphere in vivo. Soluble PirB ectodomains remarkably improved ischemic stroke model recovery by liposomal delivery system.ConclusionsThese data indicated that PirB was a significant element in the pathological process of cerebral ischemia. Therefore, PirB may act as a novel theranostic target for ischemic stroke.

show abstract

Induction of 70-kDa Heat Shock Protein and hsp70 mRNA following Transient Focal Cerebral Ischemia in the Rat

Cited by 185 publications

References 62 publications

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

Attenuation of Ischemic Brain EDEMA and Cerebrovascular Injury after Ischemic Preconditioning in the Rat

Suppression of ischemia‐induced fos expression and AP‐1 activity by an antisense oligodeoxynucleotide to c‐fos mRNA

Neuronal PirB Upregulated in Cerebral Ischemia Acts as an Attractive Theranostic Target for Ischemic Stroke

Contact Info

Product

Resources

About