GM1 Reduces Infarct Volume after Focal Cerebral Ischemia

Lazzaro, A.; Seren, M.S.; Koga, Takaki; Zanoni, R.; Schiavo, Nicola; Manev, Hari

doi:10.1006/exnr.1994.1030

Cited by 15 publications

(9 citation statements)

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“…The second implication of this study regarding the pathogenesis of AD lies in the possible role for gangliosides as neuroprotective agents. Gangliosides such as GM1 ganglioside function as neuroprotective factors in neuronal culture (48–50). When neuronal loss of gangliosides occurs, the neurons become vulnerable to various cellular stresses to include the stress of Aβ deposition to the neurons.…”

Section: Discussionmentioning

confidence: 99%

Abnormal cross‐talk between mutant presenilin 1 ( I143T, G384A ) and glycosphingolipid biosynthesis

et al. 2012

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Mutations in the presenilin 1 (PS1) gene are associated with early onset familial Alzheimer's disease (FAD). In this study, we found that the expression of mutant-PS1 in stable transfectants of SH-SY5Y neuroblastoma cells results in a reduction of the biosynthesis and steady-state levels of glucosylceramide. As an in vivo corroboration of these data, there was a significant reduction of brain glucosylceramide and gangliosides in an animal model of FAD. In mutant-PS1-transfectants (I143T, G384A), immunocytochemistry disclosed a remarkable reduction of glucosylceramide synthase (GlcT-1)-like immunoreactivity in the cells when compared with those of mock- and wild-PS1 transfectants. Immunoprecipitation of GlcT-1 protein from mutant-PS1 transfectants demonstrated a marked reduction in GlcT-1 protein, but there was no reduction in the levels of GlcT-1 mRNA. Both coprecipitation and γ-secretase inhibition experiments suggest that mutant-PS1 seems to form a complex with GlcT-1 protein and to be involved in GlcT-1 degradation, which was never found in other cell types. Thus, mutations in the PS1 gene result in profound glycosphingolipids abnormalities by abnormal molecular interaction with GlcT-1.

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Section: Discussionmentioning

confidence: 99%

Abnormal cross‐talk between mutant presenilin 1 ( I143T, G384A ) and glycosphingolipid biosynthesis

et al. 2012

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“…42 The rationale for the choice of the particular ganglioside species (GM1) as well as the dose (10 −5 M) used in these experiments was based on data obtained from studies conducted on the brain. 43 However, mammalian retinal ganglioside composition is substantially different from that of the brain, with, for example, much less GM1 and much more disialoganglioside GD3 being found in the former. 44,45 Further experiments to determine the degree of protection of other gangliosides will thus be of great interest.…”

Section: Gangliosidesmentioning

confidence: 99%

Gangliosides and Neurotrophic Growth Factors in the Retina: Molecular Interactions and Applications as Neuroprotective Agents^a

Dreyfus¹,

Sahel²,

Heidinger³

et al. 1998

Annals of the New York Academy of Sciences

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Polypeptide growth factors and gangliosides can both be considered as trophic agents involved in almost all stages of neural cell development, differentiation, survival, and pathology. In most cases their physiological roles are still not clear due to the considerable complexity in their regulation. Several growth factors [e.g., basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF)] and one species of ganglioside (GM1) have been shown to exert interactions with each other and also to exhibit neuroprotective effects against retinal ischemia in vivo and cerebral excitotoxicity in vitro. Different experimental models are used to investigate their relevance to ischemic and excitotoxic conditions in the retina, and it is shown that (1) both bFGF and EGF show very effective neuroprotection for rat retinal neurones exposed to toxic levels of glutamate or its nonphysiological agonist kainate in vitro; (2) GM1 (10(-5M) used under the same conditions does not afford protection; (3) retinal glial cells also suffer morphological perturbations following glutamate or kainate treatment, but this effect is dependent on neuron-glial interactions, indicating the existence of intermediate neuron-derived messenger molecules; (4) these glial changes can be corrected by posttreatment with either bFGF or EGF in vitro; (5) using an in vivo animal model involving anterior chamber pressure-induced ischemia in adult rats, it is shown that either pretreatment by intraperitoneal injection of GM1, or posttreatment by intraocular injection of the same ganglioside, reduces significantly histological damage to inner nuclear regions; and (6) in cultured retinal Müller glial cells the existence of molecular and metabolic interactions between both types of trophic factors is demonstrated. Hence both these groups of trophic molecules show interesting features for retinal ischemic treatment.

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“…A recent study reported that hexapeptide, EEIIMD, corresponding to amino acids 350–355 of plasminogen activator inhibitor type 1 (PAI-1), bound non-thrombolytic sites on tPA and reduced edema formation and infarction size and decreased neuronal degeneration following transient middle cerebral artery occlusion (MCAO) in young male rats [Armstead et al ., 2006]. While these findings appear promising, reservations and skepticism remain due to the lack of translation of so many other agents that showed promising results in animals but failed in the clinical setting, including calcium antagonists [Funato et al ., 1997; Liu et al ., 2004], modulation of the glutamineric and GABAergic systems [Simon and Shirashi, 1990; Turski et al ., 1998; McCracken et al ., 1993; Shuaib et al ., 1993; Snape et al ., 1993], free radical scavengers [Schmid-Elsaesser et al ., 1998; Imai et al, 2001], anti-inflammatory agents [Bertorelli et al, 1998], membrane stabilizers [Lazzaro et al ., 1994], and trophic factors [Sugimori et al ., 2001]. …”

Section: Introductionmentioning

confidence: 99%

Plasminogen activator inhibitor type 1 derived peptide, EEIIMD, diminishes cortical infarct but fails to improve neurological function in aged rats following middle cerebral artery occlusion

Tan

Kelly

et al. 2009

Brain Research

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Age is a primary risk factor in stroke that is often overlooked in animal studies. We contend that using aged animals yields insight into aspects of stroke injury and recovery that are masked, or not elicited, in younger animals. In this study, we examined effects of co-administration of a plasminogen activator inhibitor type 1 derived peptide, EEIIMD, with tissue plasminogen activator (tPA) on infarct volume and functional outcome in aged rats following a transient middle cerebral artery occlusion. Results of our study showed aged (18–20 months) rats treated with EEIIMD along with tPA had reduced cortical infarction volume. However, aged rats showed no improvement in total infarction volume, edema formation, or functional outcome as compared to aged rats administered only tPA. Young adult rats (3–4 months) treated with EEIIMD showed significant improvement in cortical and total infarction volumes, edema formation, and functional outcome. Striatal infarction volume was unaffected by EEIIMD treatment in both young adult and aged rats. These findings emphasize that physiological differences exist between young adult and aged rats and suggest that taking aging processes into account when assessing stroke may improve our ability to discern which therapeutics can be translated from bench to bedside.

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GM1 Reduces Infarct Volume after Focal Cerebral Ischemia

Cited by 15 publications

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Abnormal cross‐talk between mutant presenilin 1 ( I143T, G384A ) and glycosphingolipid biosynthesis

Abnormal cross‐talk between mutant presenilin 1 ( I143T, G384A ) and glycosphingolipid biosynthesis

Gangliosides and Neurotrophic Growth Factors in the Retina: Molecular Interactions and Applications as Neuroprotective Agents^a

Plasminogen activator inhibitor type 1 derived peptide, EEIIMD, diminishes cortical infarct but fails to improve neurological function in aged rats following middle cerebral artery occlusion

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GM1 Reduces Infarct Volume after Focal Cerebral Ischemia

Cited by 15 publications

References 0 publications

Abnormal cross‐talk between mutant presenilin 1 ( I143T, G384A ) and glycosphingolipid biosynthesis

Abnormal cross‐talk between mutant presenilin 1 ( I143T, G384A ) and glycosphingolipid biosynthesis

Gangliosides and Neurotrophic Growth Factors in the Retina: Molecular Interactions and Applications as Neuroprotective Agentsa

Plasminogen activator inhibitor type 1 derived peptide, EEIIMD, diminishes cortical infarct but fails to improve neurological function in aged rats following middle cerebral artery occlusion

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Product

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Gangliosides and Neurotrophic Growth Factors in the Retina: Molecular Interactions and Applications as Neuroprotective Agents^a