Reduction of cortical infarction and impairment of apoptosis in NGF-transgenic mice subjected to permanent focal ischemia

Guégan, Christelle; Onténiente, Brigitte; Makiura, Yaeko; Merad-Boudia, Mansouria; Ceballos-Picot, Irène; Sola, Brigitte

doi:10.1016/s0169-328x(97)00372-0

Cited by 41 publications

(28 citation statements)

References 38 publications

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“…5B Right). These results concur with a previous report that NGF reduces infarct volume and apoptosis in focal ischemia (28). Laser-Doppler flowmetry was measured over the ipsilateral parietal cortex.…”

Section: Gambogic Amide Prevents Neuronal Apoptosis and Decreases Infsupporting

confidence: 92%

“…GA is stable, and a pharmacokinetic study shows that the t 1/2 of GA in human plasma is Ϸ15.54 Ϯ 1.3 h (37). NGF may be useful for the treatment of neurodegenerative disorders such as Alzheimer's disease and stroke (28,38). Thus, our findings that gambogic amide is a TrkA agonist that prevents neuronal cell death may be clinically important for the treatment of various neurodegenerative diseases and stroke.…”

Section: Discussionmentioning

confidence: 69%

“…2D). NGF overexpression decreased infarct volume and neuronal apoptosis in transgenic mice or intraventricular-injected mice (28,29). NGF also potently protected PC12 cells from apoptosis in an oxygen-glucosedeprivation (OGD) model (30).…”

Section: Ga Binds the Cytoplasmic Juxtamembrane Domain Of Trka Receptormentioning

confidence: 99%

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Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death

Jang¹,

Okada²,

Sayeed³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

131

106

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Nerve growth factor (NGF) binds to TrkA receptor and triggers activation of numerous signaling cascades, which play critical roles in neuronal plasticity, survival, and neurite outgrowth. To mimic NGF functions pharmacologically, we developed a high-throughput screening assay to identify small-molecule agonists for TrkA receptor. The most potent compound, gambogic amide, selectively binds to TrkA, but not TrkB or TrkC, and robustly induces its tyrosine phosphorylation and downstream signaling activation, including Akt and MAPKs. Further, it strongly prevents glutamate-induced neuronal cell death and provokes prominent neurite outgrowth in PC12 cells. Gambogic amide specifically interacts with the cytoplasmic juxtamembrane domain of TrkA receptor and triggers its dimerization. Administration of this molecule in mice substantially diminishes kainic acid-triggered neuronal cell death and decreases infarct volume in the transient middle cerebral artery occlusion model of stroke. Thus, gambogic amide might not only establish a powerful platform for dissection of the physiological roles of NGF and TrkA receptor but also provide effective treatments for neurodegenerative diseases and stroke.neurotrophic effect ͉ nerve growth factor ͉ ligand ͉ receptor dimerization

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Section: Gambogic Amide Prevents Neuronal Apoptosis and Decreases Infsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 69%

See 1 more Smart Citation

Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death

Jang¹,

Okada²,

Sayeed³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

131

106

View full text Add to dashboard Cite

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“…Neuroprotective effects of nerve growth factor (NGF) in cerebral ischemia have been demonstrated in vitro and in vivo (Shigeno et al, 1991;Guegan et al, 1998). Although neutrophins like NGF or brain-derived neurotrophic factor (BDNF) are expressed in neurons, there is in vitro evidence for NGF production and NGF-like activity in astrocytes (Furukawa et al, 1986) and in vivo studies confirmed NGF expression in astrocyte-like cells after brain injury (Bakhit et al, 1991;Lee et al, 1998).…”

Section: Nerve Growth Factor and Thioredoxinmentioning

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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“…Given recent interest in using transgenic mice for stroke research, [23][24][25][26][27][28][29] the present study investigated the effects of motor cortex stroke on skilled reaching in mice. The mice were trained to reach through a slot for food, and their performance was video recorded before and after a cortex stroke produced by pial stripping.…”

mentioning

confidence: 99%

Quantitative and Qualitative Impairments in Skilled Reaching in the Mouse ( Mus musculus ) After a Focal Motor Cortex Stroke

Farr

Whishaw

2002

Stroke

151

149

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Background and Purpose-Skilled reaching movements are an important aspect of human motor behavior but are impaired after motor system stroke. The purpose of this study was to document skilled movements in mice before and after a focal motor cortex stroke for the purpose of developing a mouse model of human stroke. Methods-Male C57/BL6 mice were trained to reach with a forelimb for food pellets and then given a motor cortex stroke, induced by pial stripping, contralateral to their preferred reaching limb. Reaching success and the movements used in reaching were analyzed by frame-by-frame inspection of presurgical and postsurgical video records. Results-Reaching success was severely impaired after the stroke. Improvement in success over 2 postsurgical weeks was moderate. Analysis of 10 movement components comprising reaches pre-and postsurgically indicated that most of the rotatory movements of the limb used for aiming, advancing, pronating, and supinating the paw were impaired. When successful reaches did occur, body movements that compensated for the impairments in limb rotatory movements aided them. Conclusions-The results indicate that skilled reaching in the mouse is impaired by focal motor cortex stroke and they suggest that the mouse, and the skilled reaching task, provides an excellent model for studying impairments, compensation, and recovery after motor system stroke.

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Reduction of cortical infarction and impairment of apoptosis in NGF-transgenic mice subjected to permanent focal ischemia

Cited by 41 publications

References 38 publications

Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death

Gambogic amide, a selective agonist for TrkA receptor that possesses robust neurotrophic activity, prevents neuronal cell death

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

Quantitative and Qualitative Impairments in Skilled Reaching in the Mouse ( Mus musculus ) After a Focal Motor Cortex Stroke

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