A mouse model of focal cerebral ischemia for screening neuroprotective drug effects

Backhauß, Cord; Karkoutly, Chourouk; Welsch, M.; Krieglstein, Josef

doi:10.1016/1056-8719(92)90017-u

Cited by 89 publications

(38 citation statements)

References 13 publications

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“…A thin layer of bone was preserved to protect the dura mater and the cortical surface against mechanical damage and thermal injury, and the remaining bone was removed. The MCA was occluded by electrocoagulation (Backhauss et al, 1992). Sham-operated animals were subjected to the same anesthesia and surgical procedure, except for MCAO.…”

Section: Permanent Focal Ischemia In Micementioning

confidence: 99%

Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

Moyanova

Mastroiacovo

Kortenska

et al. 2010

J Cereb Blood Flow Metab

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We examined the influence of type 4 metabotropic glutamate (mGlu4) receptors on ischemic brain damage using the permanent middle cerebral artery occlusion (MCAO) model in mice and the endothelin-1 (Et-1) model of transient focal ischemia in rats. Mice lacking mGlu4 receptors showed a 25% to 30% increase in infarct volume after MCAO as compared with wild-type littermates. In normal mice, systemic injection of the selective mGlu4 receptor enhancer, N-phenyl-7-(hydroxyimino) cyclopropa[b]chromen-1a-caboxamide (PHCCC; 10 mg/kg, subcutaneous, administered once 30 minutes before MCAO), reduced the extent of ischemic brain damage by 35% to 45%. The drug was inactive in mGlu4 receptor knockout mice. In the Et-1 model, PHCCC administered only once 20 minutes after ischemia reduced the infarct volume to a larger extent in the caudate/putamen than in the cerebral cortex. Ischemic rats treated with PHCCC showed a faster recovery of neuronal function, as shown by electrocorticographic recording and by a battery of specific tests, which assess sensorimotor deficits. These data indicate that activation of mGlu4 receptors limit the development of brain damage after permanent or transient focal ischemia. These findings are promising because selective mGlu4 receptor enhancers are under clinical development for the treatment of Parkinson's disease and other central nervous system disorders.

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Section: Permanent Focal Ischemia In Micementioning

confidence: 99%

Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

Moyanova

Mastroiacovo

Kortenska

et al. 2010

J Cereb Blood Flow Metab

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“…A considerable number of pharmacological studies revealed that Kava and kavalactones showed various biological activities such as antithrombotic, 15) spasmolytic, 16) neuroprotective, 17) anxiolytic, 18) and anticonvulsive, 19) and TNF-a release inhibitory activities. 7) However the melanogenesis stimulatory effect of Kava on B16 melanoma cells has not been reported.…”

Section: Resultsmentioning

confidence: 99%

Melanogenesis Stimulation in Murine B16 Melanoma Cells by Kava (Piper methysticum) Rhizome Extract and Kavalactones

Matsuda

Hirata

Kawaguchi

et al. 2006

Biological & Pharmaceutical Bulletin

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Melanogenesis stimulation activity of aqueous ethanolic extracts obtained from several different parts of five Piper species, namely Piper longum, P. kadsura, P. methysticum, P. betle, and P. cubeba, were examined by using cultured murine B16 melanoma cells. Among them, the extract of P. methysticum rhizome (Kava) showed potent stimulatory effect on melanogenesis as well as P. nigrum leaf extract. Activity-guided fractionation of Kava extract led to the isolation of two active kavalactones, yangonin (2) and 7,8-epoxyyangonin (5), along with three inactive kavalactones, 5,6-dehydrokawain (1), (؉)-kawain (3) and (؉)-methysticin (4), and a glucosylsterol, daucosterin (6). 7,8-Epoxyyangonin (5) showed a significant stimulatory effect on melanogenesis in B16 melanoma cells. Yangonin (2) exhibited a weak melanogenesis stimulation activity.

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“…For terminal transferase biotinylated-UTP nick end labeling (TUNEL) staining, the animals were snap frozen in situ (23), and the brains were removed in a cold cabinet and cut into 20-m-thick coronal cryosections. For intracerebral transplantation experiments, the MCA was exposed by a temporal approach and permanently occluded by bipolar coagulation (24). The animal experiments were done in accordance with the animal protection guidelines approved by the governmental authorities within approved animal experiment proposals.…”

Section: Methodsmentioning

confidence: 99%

Hepatocyte Growth Factor/c-MET Axis-mediated Tropism of Cord Blood-derived Unrestricted Somatic Stem Cells for Neuronal Injury

Trapp

Kögler

El-Khattouti

et al. 2008

Journal of Biological Chemistry

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An under-agarose chemotaxis assay was used to investigate whether unrestricted somatic stem cells (USSC) that were recently characterized in human cord blood are attracted by neuronal injury in vitro. USSC migrated toward extracts of postischemic brain tissue of mice in which stroke had been induced. Moreover, apoptotic neurons secrete factors that strongly attracted USSC, whereas necrotic and healthy neurons did not. Investigating the expression of growth factors and chemokines in lesioned brain tissue and neurons and of their respective receptors in USSC revealed expression of hepatocyte growth factor (HGF) in post-ischemic brain and in apoptotic but not in necrotic neurons and of the HGF receptor c-MET in USSC. Neuronal lesion-triggered migration was observed in vitro and in vivo only when c-MET was expressed at a high level in USSC. Neutralization of the bioactivity of HGF with an antibody inhibited migration of USSC toward neuronal injury. This, together with the finding that human recombinant HGF attracts USSC, document that HGF signaling is necessary for the tropism of USSC for neuronal injury. Our data demonstrate that USSC have the capacity to migrate toward apoptotic neurons and injured brain. Together with their neural differentiation potential, this suggests a neuroregenerative potential of USSC. Moreover, we provide evidence for a hitherto unrecognized pivotal role of the HGF/c-MET axis in guiding stem cells toward brain injury, which may partly account for the capability of HGF to improve function in the diseased central nervous system.Endogenous as well as transplanted stem cells have the capacity to migrate toward lesions in the adult central nervous system and may have the therapeutic potential to enhance regeneration after brain injury. Therefore, cell replacement therapy has received considerable attention as a future treatment for brain injury such as stroke (1-5). Various cellular transplantation strategies have shown some efficacy in treating different types of central nervous system injuries in animal models (6 -8). The mechanisms underlying the observed beneficial effects of these therapies have not been elucidated. The most straightforward idea is that stem cells differentiate into mature cell types and simply replace the lost tissue. However, there is increasing evidence that transplanted cells may secrete neurotrophic or neuroprotective factors that can counteract degeneration or promote regeneration (9 -13).Concerning stem cell-based therapies various kinds of stem cells, i.e. embryonic, fetal, and adult stem cells, are under investigation. Although embryonic and fetal stem cells may have the broadest differentiation potential (1, 14), their use raises serious biological, ethical, and legal questions limiting a widespread clinical use of these cells at present. Moreover, allogeneic transplantation of embryonic stem cells was shown to produce highly malignant teratocarcinomas at the site of implantation in mice (15). Faced with these difficulties, investigators identified and evaluated...

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A mouse model of focal cerebral ischemia for screening neuroprotective drug effects

Cited by 89 publications

References 13 publications

Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

Protective Role for Type 4 Metabotropic Glutamate Receptors against Ischemic Brain Damage

Melanogenesis Stimulation in Murine B16 Melanoma Cells by Kava (Piper methysticum) Rhizome Extract and Kavalactones

Hepatocyte Growth Factor/c-MET Axis-mediated Tropism of Cord Blood-derived Unrestricted Somatic Stem Cells for Neuronal Injury

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