Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats

Fisher, Marc; Meadows, Mary–Ellen; Do, Tuyen; Weise, Jens; Trubetskoy, Vladimir S.; Charette, Marc; Finklestein, Seth P.

doi:10.1038/jcbfm.1995.121

Cited by 170 publications

(91 citation statements)

References 24 publications

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“…It increases neuronal survival, has trophic effects on brain glial and endothelial cells and is a potent systemic and cerebral vasodilator. 62,63 It has been demonstrated that administration of bFGF after permanent 64 or transient MCA occlusion 65 significantly reduced infarct volumes. Although a phase I trial in stroke patients was promising, the U.S. phase II trial was halted because patients that received bFGF did worse compared to the placebo group, and the companion European trial failed to show efficacy.…”

Section: Neurotrophic Factorsmentioning

confidence: 99%

Neuroprotection for ischemic stroke: Two decades of success and failure

Al-Khoury

Zivin

2004

Neurotherapeutics

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Summary: Alteplase (rt-PA) is the first therapy successfully developed for acute stroke therapy. The success of rt-PA spurred development of new avenues for acute stroke management. For the last two decades, a great deal of attention has been paid to neuroprotective therapies. Initial preclinical studies demonstrated numerous drugs are effective for treating acute stroke in animal models; however, subsequent clinical trials have been frustrating, and none of the agents has proven effective. The various outcomes of preclinical and clinical trials have been the subject of much discussion. In this article, we review some key neuroprotective trials and the possible reasons for their failures. By identifying the discrepancies between preclinical studies and clinical trials, we may be able to set guidelines for future effective trials.

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Section: Neurotrophic Factorsmentioning

confidence: 99%

Neuroprotection for ischemic stroke: Two decades of success and failure

Al-Khoury

Zivin

2004

Neurotherapeutics

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“…53−55 In animal models (rat and cat), early administration (less than 1 to 3 h, iv infusion) reduced the infarct volumes in the MCAO side of the cerebral hemisphere. 10,13,56 On the other hand, delayed treatment with bFGF (started 1 day postinfarct, intracisternally) in the MCAO rat model did not ameliorate the cerebral infarct volumes but resulted in an enhancement of the recovery of the cerebral motor functions of the contralateral limbs in cases of prolonged survival.…”

Section: ■ Discussionmentioning

confidence: 99%

SUN11602, a Novel Aniline Compound, Mimics the Neuroprotective Mechanisms of Basic Fibroblast Growth Factor

Murayama

Kadoshima

Takemoto

et al. 2012

ACS Chem. Neurosci.

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Basic fibroblast growth factor (bFGF) offers some measure of protection against excitotoxic neuronal injuries by upregulating the expression of the calcium-binding protein calbindin-D28k (Calb). The newly synthesized small molecule 4-({4- [[(4-amino-2,3,5,6-tetramethylanilino) ) and wild-type (WT) mice. In WT mice, SUN11602 and bFGF increased the levels of newly synthesized Calb in cerebrocortical neurons and suppressed the glutamate-induced rise in intracellular Ca 2+

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“…The highly discriminatory and selective BBB is relatively impermeable to compounds with M r greater than 400-500 daltons. 38,39) In the suture-occlusion model of MCA in rats, BBB disruption was reported to occur 2-4 h after occlusion, 40) leading to vasogenic cerebral edema. On the other hand, BBB disruption enables large molecules to enter the brain.…”

Section: Discussionmentioning

confidence: 99%

Cyanine Dyes Attenuate Cerebral Ischemia and Reperfusion Injury in Rats

Koya‐Miyata

Ohta

Akita

et al. 2010

Biological & Pharmaceutical Bulletin

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Ischemic stroke is a leading cause of death and long-lasting disability. However, therapeutic options for acute ischemic stroke remain very limited.1) Ischemic stroke triggers a cascade of pathophysiological events including excitotoxicity, ionic imbalance, oxidative stress, and apoptosis-like cell death ending in destructive neurodegeneration.2-4) The cumulative evidence suggests involvement of reactive oxygen species (ROS) in the pathogenesis of ischemic injury.5) Several components of ROS including superoxides ( · O 2 Ϫ ), hydroxyl radicals ( · OH), and hydrogen peroxide (H 2 O 2 ) are generated by post-ischemia/reperfusion injury. They are known to induce DNA damage, lipid peroxidation, disruption of blood brain-barrier (BBB), and microglial activation in the ischemic tissue. The rat middle cerebral artery occlusion (MCAO) model mimics the pathophysiological consequences induced by ischemic stroke in humans and thus has been frequently employed.Cyanine photosensitizing dyes have been shown to have various biological activities, such as antimicrobial, antioxidant, macrophage activation, and oxidative phosphorylation uncoupling activities.6-9) Some of those dyes have been used as immunomodulators to treat allergy and rheumatoid arthritis, and to promote wound-healing. [10][11][12][13] It was reported that platonin, a kind of cyanine dye, suppressed acute endotoxemia in rats by inhibiting inflammatory cytokine release from lipopolysaccharide (LPS)-stimulated lymphocytes.14,15) Recent studies suggested that neutrophil infiltration and release of inflammatory cytokines (i.e., interleukin (IL)-1b, IL-6, IL-17, IL-23, and tumor necrosis factor-a) participate in a secondary mechanism of brain injury following ischemia and reperfusion. [16][17][18] Because there is substantial evidence showing that immune responses play crucial roles in mediating neuronal damage in the animal model of stroke, 16) it is reasonable to expect that cyanine dyes with anti-inflammatory properties could protect against neuroinflammatory events. To our knowledge, little is not known whether these dyes are pharmacologically active against ischemia-induced brain injury or neurodegenerative disorders. To explore this potential of cyanine dyes, it would be of interest to examine their effects in the MCAO model, an animal model of ischemic stroke. Prior to the in vivo evaluation, we screened more than 250 cyanine dyes for their neurotrophin-like activity (such as potentiation of neurite outgrowth in neural cells) and found that NK-4 (Fig. 1A), NK-150 (Fig. 1B), and some other related compounds showed remarkable neurite outgrowth-promoting activity in PC12 neural cells. NK-4 and NK-150 are thought to be safe compounds since they showed no acute toxicity when orally-administrated to mice at a dose of 2000 mg/kg (our unpublished observation). In the present report, we further examined NK-4 and NK-150 for their ability to promote nerve growth factor (NGF)-primed neurite outgrowth and for free radical scavenging activity in vitro. We also examined the...

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Delayed Treatment with Intravenous Basic Fibroblast Growth Factor Reduces Infarct Size following Permanent Focal Cerebral Ischemia in Rats

Cited by 170 publications

References 24 publications

Neuroprotection for ischemic stroke: Two decades of success and failure

Neuroprotection for ischemic stroke: Two decades of success and failure

SUN11602, a Novel Aniline Compound, Mimics the Neuroprotective Mechanisms of Basic Fibroblast Growth Factor

Cyanine Dyes Attenuate Cerebral Ischemia and Reperfusion Injury in Rats

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