Infarct tolerance induced by intra-cerebral infusion of recombinant brain-derived neurotrophic factor

Yanamoto, Hiroji; Nagata, Izumi; Sakata, Masahiro; Zhang, Z.; Tohnai, Norimitsu; Sakai, Hideki; Kikuchi, Hiroe

doi:10.1016/s0006-8993(00)01966-1

Cited by 54 publications

(25 citation statements)

References 48 publications

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“…These observations are consistent with our findings that Ndrg4 Ϫ/Ϫ mice have lower amounts of cortex BDNF than Ndrg4 ϩ/ϩ and impaired spatial learning and memory function. Because BDNF also increases the survivability of neurons against ischemia, decreased levels of BDNF in the Ndrg4 Ϫ/Ϫ cortex can explain the enlarged lesion sizes that appeared after the stress induced by temporary focal ischemia (23)(24)(25)(26). BDNF-mediated production of prostacyclin (36) may be associated with the neuronal vulnerabilities of the Ndrg4 Ϫ/Ϫ mice because prostacyclin has a potent neuroprotective effect against focal cerebral ischemia (37).…”

Section: Discussionmentioning

confidence: 99%

“…BDNF also has neuroprotective action in models of ischemia. Increased BDNF levels in the brain for an appropriate period prior to the ischemic insult increases the resistance of the brain against lethal stresses caused by severe ischemia (23,24). In contrast, a deficiency in endogenous BDNF renders the brain more susceptible to ischemic injury (25) and more suppressive to infarct tolerance by the preconditioning of spreading depression (26).…”

Section: N-myc Downstream-regulated Gene (Ndrg)mentioning

confidence: 99%

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NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Yamamoto

Kokame

Okuda

et al. 2011

Journal of Biological Chemistry

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The N-myc downstream-regulated gene (NDRG) family consists of four related proteins, NDRG1-NDRG4, in mammals. We previously generated NDRG1-deficient mice that were unable to maintain myelin sheaths in peripheral nerves. This condition was consistent with human hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, caused by a nonsense mutation of NDRG1. In contrast, the effects of genetic defects of the other NDRG members remain unknown. In this study, we focused on NDRG4, which is specifically expressed in the brain and heart. In situ mRNA hybridization on the brain revealed that NDRG4 was expressed in neurons of various areas. We generated NDRG4-deficient mice that were born normally with the expected Mendelian frequency. Immunochemical analysis demonstrated that the cortex of the NDRG4-deficient mice contained decreased levels of brain-derived neurotrophic factor (BDNF) and normal levels of glial cell line-derived neurotrophic factor, NGF, neurotrophin-3, and TGF-␤1. Consistent with BDNF reduction, NDRG4-deficient mice had impaired spatial learning and memory but normal motor function in the Morris water maze test. When temporary focal ischemia of the brain was induced, the sizes of the infarct lesions were larger, and the neurological deficits were more severe in NDRG4-deficient mice compared with the control mice. These findings indicate that NDRG4 contributes to the maintenance of intracerebral BDNF levels within the normal range, which is necessary for the preservation of spatial learning and the resistance to neuronal cell death caused by ischemic stress. N-myc downstream-regulated gene (NDRG)3 family members NDRG1-NDRG4 are intracellular proteins, consist of 340 -394 amino acid residues, and share 53-65% sequence identity with each other. Furthermore, accumulating evidence implicates their roles in development, cancer metastasis, and the immune system (1-5).We originally identified RTP (NDRG1) as a homocysteineresponsive gene in human umbilical vein endothelial cells (6), which is also called DRG1, Cap43, Rit42, Ndr1, and PROXY-1. NDRG1 expression is induced by a number of conditions, such as DNA damage, hypoxia, and intracellular calcium ion elevation (4). Overexpression of NDRG1 suppresses the metastatic potency of some types of cancer cells (4) and enhances the degranulation of mast cells in response to various stimuli (7). A nonsense mutation of NDRG1 causes hereditary motor and sensory neuropathy, Charcot-Marie-Tooth disease type 4D, which presents as distal muscle wasting and atrophy, foot and hand deformities, tendon areflexia, sensory loss, and deafness in afflicted individuals (8). We previously generated NDRG1-deficient mice and revealed the essential role of NDRG1 in the cytoplasm of Schwann cells for the maintenance of myelin sheaths in peripheral nerves (9). A frame shift deletion of Ndrg1 in Greyhounds also causes polyneuropathy (10).Similar to NDRG1, the expression of NDRG2 is induced by stress conditions such as hypoxia (1). NDRG2 expression is upregulated in cort...

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Section: Discussionmentioning

confidence: 99%

Section: N-myc Downstream-regulated Gene (Ndrg)mentioning

confidence: 99%

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Yamamoto

Kokame

Okuda

et al. 2011

Journal of Biological Chemistry

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“…BDNF was induced after ischemic preconditioning Truettner et al, 2002) and ischemic tolerance was mimicked by the application of BDNF in vivo (Yanamoto et al, 2000). Neurotrophins, expressed in astrocytes and regulated in an IL-6-dependent manner, play a protective role during cerebral ischemia as well, although experimental evidence suggests that NT4 is less potent than BDNF in promoting brain survival after stroke (Marz et al, 1999;Endres et al, 2003).…”

Section: Brain-derived Neurotrophic Factor (Bdnf)mentioning

confidence: 99%

Neuroprotective role of astrocytes in cerebral ischemia: Focus on ischemic preconditioning

Trendelenburg

Dirnagl

2005

Glia

233

167

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Following focal cerebral ischemia ("stroke") a complex and dynamic interaction of vascular cells, glial cells, and neurons determines the extent of the ensuing lesion. Traditionally, the focus has been on mechanisms of damage, while recently it has become clear that endogenous mechanisms of protection are equally important for the final outcome. Glial cells, in particular astrocytes, have always been viewed as supporters of neuronal function. Only recently a very active role for glial cells has been emerging in physiology and pathophysiology. Not surprisingly, then, specific protective pathways have been identified by which these cells can protect or even help to regenerate brain tissue after acute insults. However, as exemplified by the existence of the glial scar, which forms around lesioned brain tissue, is composed mainly of astrocytes and plays a key role in regeneration failure, it is an oversimplification to assign merely protective functions to astrocytes. The present review will discuss the role of astrocytes in ischemic brain injury with a focus on neuroprotection in general. In this context we will consider particularly the phenomenon of "ischemic tolerance," which is an experimental paradigm helpful in discriminating destructive from protective mechanisms after cerebral ischemia.

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“…Intracerebral infusion of BDNF induces cerebral tolerance [85] and reduces infarct size in focal ischemia [86,87]. Intravenous administration of BDNF reduces infarct size in rodents by altering the Bcl-2/Bax ratio in the penumbra [88] and administration of BDNF into the area of the infarct following permanent middle cerebral artery occlusion reduces lesion size [89].…”

Section: Brain Preconditioning By 2-deoxy-d-glucosementioning

confidence: 99%

“…Brainderived neurotrophic factor is an endogenous compound whose level could be straightforwardly directly or indirectly regulated. BDNF induces anti-apoptotic mechanisms after stroke and reduces infarct size and secondary neuronal cell death [83][84][85]. Moreover, in intact animals, BDNF is a potent stimulator of adult neurogenesis: in a model of photothrombotic ischemia, BDNF intravenous infusion prior to the lesion increases the number of neurons in the hippocampus [86].…”

Section: Why Brain Preconditioning Toward Bdnf Regulation Could Lead mentioning

confidence: 99%

Brain Adaptation to Stressful Stimuli: A New Perspective on Potential Therapeutic Approaches Based on BDNF and NMDA Receptors

Marini

Popolo²,

Pan³

et al. 2008

CNSNDDT

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A variety of sublethal or stressful stimuli induce a phenomenon in the brain known as tolerance, an adaptive response that protects the brain against the same stress, or against a different stress (cross-tolerance). Understanding the molecular mechanisms of brain preconditioning holds promise in developing innovative therapies to prevent and treat neurodegenerative disorders, particularly ischemic stroke. Many of the detailed steps involved in tolerance and cross-tolerance are unknown. It is also likely that different stressors differentially regulate sets of genes, transcription factors, and signal transduction pathways that depend upon the molecules that are released in response to the stressor, activation of particular receptors, and the surrounding milieu. The focus of this review is to highlight a few examples of stimuli that induce tolerance: 1) cortical spreading depression; 2) 3-nitropropionic acid; and 3) 2-deoxy-D-glucose. We will summarize by discussing one pathway where intracellular mediators may converge to upregulate intrinsic neuronal survival pathways to promote survival by resisting damage. This mechanism, activation of N-methyl-D-aspartate receptors and its integral relationship with brain-derived neurotrophic factor, may be a critical and general mechanism developed in brain to respond to stressful stimuli.

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Infarct tolerance induced by intra-cerebral infusion of recombinant brain-derived neurotrophic factor

Cited by 54 publications

References 48 publications

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

Neuroprotective role of astrocytes in cerebral ischemia: Focus on ischemic preconditioning

Brain Adaptation to Stressful Stimuli: A New Perspective on Potential Therapeutic Approaches Based on BDNF and NMDA Receptors

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