Effects of accumulation of phosphocreatine on utilization and restoration of high-energy phosphates during anoxia and recovery in thin hippocampal slices from the guinea pig

Yoneda, Kazushi; Arakawa, Takamitsu; Asaoka, Yoshinori; Fukuoka, Yoshihiro; Kinugasa, Kazuhiro; Takimoto, K.; Okada, Yasuhiro

doi:10.1016/0014-4886(83)90256-x

Cited by 18 publications

(14 citation statements)

References 11 publications

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“…6). In fact, creatine administration in brain slices leads to an increase in phospho-creatine [4,29], and the latter acts as an energy reserve that prevents or delays the depletion of ATP [13,31]. Thus, the reversing effect of creatine on oleammide-induction slowing of conduction velocity supports the hypothesis that such reduction may have been caused by prevention of ATP transfer through glia-neuron gap junctions.…”

Section: Discussionmentioning

confidence: 51%

A Novel Hypothesis About Mechanisms Affecting Conduction Velocity of Central Myelinated Fibers

et al. 2011

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The hypothesis that gap junctions are implicated in facilitating axonal conduction has not yet been experimentally demonstrated at the electrophysiological level. We found that block of gap junctions with oleammide slows down axonal conduction velocity in the hippocampal Schaffer collaterals, a central myelinated pathway. Moreover, we explored the possibility that support by the oligodendrocyte to the axon involves energy metabolism, a hypothesis that has been recently proposed by some of us. In agreement with this hypothesis, we found that the effect of oleammide was reversed by pretreatment with creatine, a compound that is known to increase the energy charge of the tissue. Moreover, conduction velocity was also slowed down by anoxia, a treatment that obviously decreases the energy charge of the tissue, and by ouabain, a compound that blocks plasma membrane Na/K-ATPase, the main user of ATP in the brain. We hypothesize that block of gap junctions slows down conduction velocity in central myelinated pathways because oligodendrocytes synthesize ATP and transfer it to the axon through gap junctions.

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Section: Discussionmentioning

confidence: 51%

A Novel Hypothesis About Mechanisms Affecting Conduction Velocity of Central Myelinated Fibers

et al. 2011

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“…However, neuronal phosphocreatine content is limited, and soon after complete anoxia or ischemia phosphocreatine is depleted, too [1]. Brain phosphocreatine is substantially increased by treatment with creatine [4,5], and it has been repeatedly shown that creatine pretreatment protects against anoxic damage in vitro [6][7][8][9][10]. However, in contrast to this clear and established efficacy in in vitro models of anoxia, pretreatment with creatine in in vivo models of stroke had until recently yielded conflicting results, reporting both efficacy [11] and lack of it [12].…”

Section: Acsfmentioning

confidence: 98%

Protective Effects of Some Creatine Derivatives in Brain Tissue Anoxia

et al. 2007

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Some derivatives more lipophylic than creatine, thus theoretically being capable to better cross the blood-brain barrier, were studied for their protective effect in mouse hippocampal slices. We found that N-amidino-piperidine is harmful to brain tissue, and that phosphocreatine is ineffective. Creatine, creatine-Mg-complex (acetate) and phosphocreatine-Mg-complex (acetate) increased the latency to population spike disappearance during anoxia. Creatine and creatine-Mg-complex (acetate) also increased the latency of anoxic depolarization, while the delay induced by phosphocreatine-Mg-complex (acetate) was of borderline significance (P = 0.056). Phosphocreatine-Mg-complex (acetate) significantly reduced neuronal hyperexcitability during anoxia, an effect that no other compound (including creatine itself) showed. For all parameters except reduced hyperexcitability the effects statistically correlated with tissue levels of creatine or phosphocreatine. Summing up, exogenous phosphocreatine and N-amidino piperidine are not useful for brain protection, while chelates of both creatine and phosphocreatine do replicate some of the known protective effects of creatine. In addition, phosphocreatine-Mg-complex (acetate) also reduced neuronal hyperexcitability during anoxia.

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“…Despite the presence of a dedicated transporter, its crossing of the BBB is low and partial and its crossing of the brain cells’ plasma membranes is also too slow to allow a rapid use in acute stroke. In fact, even in in vitro brain slices, a 2–3 hr incubation is needed to reach a neuroprotective tissue concentration of Cr . Thus, Cr when systemically administered is not able to rapidly increase its cerebral concentration .…”

Section: Creatine and Cerebral Ischemiamentioning

confidence: 99%

Therapeutic Use of Creatine in Brain or Heart Ischemia: Available Data and Future Perspectives

Perasso

Spallarossa

Ruggeri

et al. 2011

Medicinal Research Reviews

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Creatine (Cr) is essential in safeguarding ATP levels and in moving ATP from its production site (mitochondria) to the cytoplasmic regions where it is used. Moreover, it has effects unrelated to energy metabolism, such as free radical scavenging, antiapoptotic action, and protection against excitotoxicity. Recent research has studied Cr-derived compounds (Cr benzyl ester and phos-pho-Cr-magnesium complex) that reproduce the neuroprotective effects of Cr while better crossing the neuronal plasma membrane and, hopefully, the blood-brain barrier (BBB). Intracellular levels of Cr can be increased by incubation with Cr or some of its derivatives, and this increase is protective against anoxic or ischemic damage. A large amount of experimental evidence shows that pretreatment with Cr is capable of reducing the damage induced by ischemia or anoxia in both heart and brain, and that such treatment may also be useful even after stroke or myocardial infarction (MI) has already occurred. Cr has been safely administered to patients affected by several neurological diseases, yet it has never been tested in human brain ischemia, the condition where its rationale is strongest. Phosphocreatine (PCr) has been administered after human MI, where it proved to be safe and probably helpful. Cr should be tested in the prophylactic protection against human brain ischemia and either Cr or PCr should be further tested in MI. Moreover, Cr- or PCr-derived drugs should be developed in order to overcome these molecules' limitations in crossing the BBB and the cell plasma membrane.

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Effects of accumulation of phosphocreatine on utilization and restoration of high-energy phosphates during anoxia and recovery in thin hippocampal slices from the guinea pig

Cited by 18 publications

References 11 publications

A Novel Hypothesis About Mechanisms Affecting Conduction Velocity of Central Myelinated Fibers

A Novel Hypothesis About Mechanisms Affecting Conduction Velocity of Central Myelinated Fibers

Protective Effects of Some Creatine Derivatives in Brain Tissue Anoxia

Therapeutic Use of Creatine in Brain or Heart Ischemia: Available Data and Future Perspectives

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