Prolonged anoxic depolarization exacerbates NADH hyperoxidation and promotes poor electrical recovery after anoxia in hippocampal slices

Pérez-Pinzón, Miguel A.; Mumford, Patricia L.; Sick, Thomas J.

doi:10.1016/s0006-8993(97)01438-8

Cited by 25 publications

(24 citation statements)

References 35 publications

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“…In fact, the fEPSP responses in all age groups recovered to greater than control values, which suggest that mild synaptic potentiation occurred. A similar result was obtained in which 30 s of hypoxia post-hsd in hippocampal slices resulted in higher fEPSP amplitudes compared to control slices (Perez-Pinzon et al, 1998b).…”

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomesupporting

confidence: 83%

“…Neuronal recovery in the CA1 region of the hippocampus has been shown to be more sensitive to the length of time following the onset of hsd than to the total time exposed to hypoxia (Perez-Pinzon et al, 1998b). We have shown that slices from all ages are tolerant to 15 s of further hypoxia following hsd.…”

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomementioning

confidence: 76%

“…Extending the length of post-hsd hypoxia to 2.5 min in this study resulted in depressed synaptic activity and therefore reduced neuronal recovery in slices from the oldest age groups (12-20 and >22 months) while slices from 1 to 2 and 3 to 6 months old rats were more resistant (and recovered to ≥95%). In a previous study, shorter periods of anoxic depolarization (1 min) caused greater than 50% suppression of synaptic activity in adult hippocampal slices while 2 min resulted in <20% recovery of the evoked potential (Perez-Pinzon et al, 1998b). The reasons for the differences in susceptibility between these two studies are not directly apparent since slice preparation conditions and the types of chambers used were very similar.…”

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomementioning

confidence: 89%

“…A number of previous studies in brain slices have provided evidence that neuronal recovery is worsened as the duration of hypoxia following hsd is increased (Balestrino et al, 1989(Balestrino et al, , 1999Balestrino and Somjen, 1986;Jing et al, 1991;Kawasaki et al, 1988;Lee and Lowenkopf, 1993;Perez-Pinzon et al, 1998b;Roberts and Sick, 1988;Tombaugh, 1994;Watson and Lanthorn, 1995). Extending the length of post-hsd hypoxia to 2.5 min in this study resulted in depressed synaptic activity and therefore reduced neuronal recovery in slices from the oldest age groups (12-20 and >22 months) while slices from 1 to 2 and 3 to 6 months old rats were more resistant (and recovered to ≥95%).…”

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomementioning

confidence: 99%

“…Recordings made in intact brains as well as in brain slices following either transient ischemic or hypoxic episodes revealed a decrease of NADH fluorescence and cytochrome a,a 3 reflectance significantly below control levels, which has been interpreted as hyperoxidation of intra-mitochondrial oxidative enzymes Duckrow et al, 1981;Feng et al, 1998;Paschen et al, 1985;Perez-Pinzon et al, 1998a, 1997a, 1998bPulsinelli et al, 1982;Rosenthal et al, 1995Rosenthal et al, , 1997Siesjo, 1981;Tanaka et al, 1986;Welsh et al, 1991;Welsh et al, 1982). The alternative explanation of a depletion of the electron carrier pool has been rejected by other authors .…”

Section: Introductionmentioning

confidence: 97%

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NADH hyperoxidation correlates with enhanced susceptibility of aged rats to hypoxia

Foster¹,

Margraf²,

Turner³

2008

Neurobiology of Aging

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Aging increases mitochondrial dysfunction and susceptibility to hypoxia. Previous reports have indicated an association between post-hypoxic hyperoxidation of intra-mitochondrial enzymes and delayed neuronal injury. Therefore we investigated the relationship between NADH fluorescence and neuronal function during and after hypoxia across the lifespan. Hippocampal slices were prepared from adult (1 to >22 months) F344 rats. NADH fluorescence, extracellular voltage and tissue PO 2 were recorded from the CA1 region during hypoxia (95% N 2 ) of various lengths following onset of hypoxic spreading depression (hsd). Slices from younger rats recovered evoked neuronal responses to a greater degree and exhibited less hyperoxidation after a hypoxic episode, than slices from older rats. However, the use of Ca 2+ free-media in slices from >22 month old rats improved recovery and delayed NADH hyperoxidation (2.5 min hypoxia after hsd). Post-hypoxic decrease of NADH fluorescence (hyperoxidation) was age dependent and correlated with decreased neuronal recovery. Slices exposed to repeated hypoxic episodes yielded data suggesting depletion of the NAD + pool, which may have contributed to the deterioration of neuronal function.

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Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomesupporting

confidence: 83%

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomementioning

confidence: 76%

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomementioning

confidence: 89%

Section: Duration Of Hypoxia (Pre-and Post-hsd) Versus Outcomementioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 3 more Smart Citations

NADH hyperoxidation correlates with enhanced susceptibility of aged rats to hypoxia

Foster¹,

Margraf²,

Turner³

2008

Neurobiology of Aging

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Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia

Emery

Ouyang

et al. 2010

Glia

102

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Brief forebrain ischemia is a model of the delayed hippocampal neuronal loss seen in patients following cardiac arrest and resuscitation. Previous studies demonstrated that selective dysfunction of hippocampal CA1 subregion astrocytes occurs hours to days before delayed neuronal death. In this study we tested the strategy of directing protection to astrocytes to protect neighboring neurons from forebrain ischemia. Two well-studied protective proteins, heat shock protein 72 (Hsp72) or superoxide dismutase 2 (SOD2), were genetically targeted for expression in astrocytes using the astrocyte-specific human glial fibrillary acidic protein (GFAP) promoter. The expression constructs were injected stereotacticly immediately above the hippocampal CA1 region on one side of the rat brain two days prior to forebrain ischemia. Cell type specific expression was confirmed by double label immunohistochemistry. When the expression constructs were injected two days before transient forebrain ischemia, the loss of CA1 hippocampal neurons observed seven days later was significantly reduced on the injected side compared with controls. This neuroprotection was associated with significantly better preservation of astrocyte glutamate transporter-1 immunoreactivity at 5-h reperfusion and reduced oxidative stress. Improving the resistance of astrocytes to ischemic stress by targeting either the cytosolic or mitochondrial compartment was thus associated with preservation of CA1 neurons following forebrain ischemia. Targeting astrocytes is a promising strategy for neuronal preservation following cardiac arrest and resuscitation.

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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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Prolonged anoxic depolarization exacerbates NADH hyperoxidation and promotes poor electrical recovery after anoxia in hippocampal slices

Cited by 25 publications

References 35 publications

NADH hyperoxidation correlates with enhanced susceptibility of aged rats to hypoxia

NADH hyperoxidation correlates with enhanced susceptibility of aged rats to hypoxia

Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia

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

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