Ischemic brain injury and cell calcium: Morphologic and therapeutic aspects

Reempts, Jos Van; Borgers, M.

doi:10.1016/s0196-0644(85)80048-2

Cited by 62 publications

(26 citation statements)

References 17 publications

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“…This seemed a reasonable assumption since the mitochondria represent a high-capacity calcium sequestration system. Calcium accumulation following transient isch emia in rats has previously been studied with the oxalate-pyriantimonate technique (Simon et al , 1984;van Reempts et al , 1984;van Reempts and Borgers, 1985). All these studies demonstrate that recirculation after transient ischemia is accompa nied by the expected appearance of calcium precip itates in neuronal mitochondria.…”

Section: Discussionmentioning

confidence: 99%

“…Any such increase in Ca 2 + i will, pre dictably, cause accumulation of calcium in mito chondria once the membrane potential is restored or AT P production is resumed (see Rasmussen and Waisman, 1983;Carafoli and Sottocasa, 1984). In confirmation, application of the oxalate-pyrianti monate technique to recirculation following tran sient ischemia has revealed calcium precipitates in mitochondria (van Reempts et al , 1984;van Reempts and Borgers, 1985;Simon et al , 1984;Dux et al , 1987;see Griffiths et al , 1983 for com parable data on seizures). However, since the cal cium load represented by the extracellular calcium is f>mall (about 300 f.LM), re-export of the calcium accumulated should not cause irreversible mito chondrial damage, unless the extracellular calcium enters at "hot spots" where calcium channels abound.…”

Section: Discussionmentioning

confidence: 99%

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Accumulation of Calcium and Loss of Potassium in the Hippocampus following Transient Cerebral Ischemia: A Proton Microprobe Study

Martins

Inamura²,

Themner³

et al. 1988

J Cereb Blood Flow Metab

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This study explored (a) whether postischemic accumulation of calcium in hippocampal neurons precedes or occurs pari passu with light microscopical signs of delayed neuronal necrosis, and (b) whether calcium initially accumulates in dendritic domains, presumed to have a high density of agonist-operated calcium channels. Transient ischemia of 10-min duration was induced in rats, and the animals were studied after 1, 2, 3, and 4 days of recovery. We measured total calcium and potassium contents in the stratum oriens, pyramidale, radiatum, and moleculare of the CA1 and CA3 sectors, using particle induced x-ray emission (PIXE) in the proton microprobe mode. The results showed significant accumulation of calcium and loss of potassium after 3 and 4 days of recovery in the CA1 sector, which developed neuronal necrosis, but not in the CA3 sector, which showed only occasional damage. In a few animals, calcium accumulation (and loss of potassium) was observed with no or only mild visible damage, but in the majority of animals the accumulation of calcium correlated to signs of neuronal necrosis. Since calcium accumulation was similar in all strata examined, the results failed to reveal preferential accumulation in dendritic or somal regions. Based on our results and those of Dux et al., we emphasize the possibility that delayed neuronal death is, at least in part, caused by increased calcium cycling of plasma membranes and gradual calcium overload of mitochondria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Accumulation of Calcium and Loss of Potassium in the Hippocampus following Transient Cerebral Ischemia: A Proton Microprobe Study

Martins

Inamura²,

Themner³

et al. 1988

J Cereb Blood Flow Metab

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“…Thus, as in the adult (Van Reempts and Borgers, 1985), alterations in Ca flux of the immature rat brain occur in two distinct phases, i.e., that which arises during the course of hypoxia-ischemia be fore the onset of neuronal destruction, and that which proceeds in parallel with the evolution of the ultimate pathologic lesion. The former alteration has been implicated as a prime initiator of those ad verse metabolic processes that culminate in tissue injury, including activation of phospholipase with the accumulation of free fatty acids and the forma tion of free radicals, which are deleterious to mem brane stability.…”

Section: Discussionmentioning

confidence: 99%

“…Using the oxalate pyroantimonate technique for the electron micro scopic visualization of intracellular Ca, showed that after allylglycine-induced status epilepticus in adult rats excess Ca accumula tion in non vulnerable neurons resolves by 60 min of recovery, whereas Ca continues to accumulate in vulnerable neurons of the hippocampus. As in status epilepticus, calcium flux into neurons also occurs during hypoxia-ischemia, which dissipates in the early recovery period (Van Reempts and Borgers, 1985). Thereafter, a secondary "Ca over load" ensues, which is associated with neuronal necrosis, at least in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…Thereafter, a secondary "Ca over load" ensues, which is associated with neuronal necrosis, at least in the hippocampus. Indeed, Ca channel blocking agents appear most efficacious in retarding the postischemic accumulation of cyto solic Ca, which, in turn, reduces the extent of de layed neuronal injury (Van Reempts and Borgers, 1985) (see below).…”

Section: Discussionmentioning

confidence: 99%

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Calcium Accumulation during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat

Stein

Vannucci

1988

J Cereb Blood Flow Metab

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Summary: An excessive accumulation of calcium in neu ronal and other tissues has been postulated to represent a "final common pathway" for cell death arising from hyp oxia-ischemia. To clarify the role of altered calcium flux into and distribution within the perinatal brain under going hypoxic-ischemic injury, 7-day postnatal rats un derwent unilateral common carotid artery ligation fol lowed by 3 h of hypoxia with 8% oxygen. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in >90% of the animals. Either before or after hypoxia-ischemia, the animals received a subcutaneous injection of [45Ca]CI2, and their brains were subjected to 45Ca autora diography at 0-1, 5, 24, and 72 h, 7 or 15 days thereafter. During hypoxia-ischemia, calcium flux into the ipsilat eral cerebral hemisphere was prominent in 13 of 14 rat pups, especially in neocortex, hippocampus, striatum, and thalamus. Calcium accumulation also occurred to a variable degree (6 of 14 animals) in the contralateral cerePerinatal cerebral hypoxic-ischemic brain damage is characterized either by selective necrosis of vulnerable neurons or infarction (Rorke, 1982;Vannucci, 1985; Volpe, 1987). Regions of immature brain especially sensitive to hypoxic-ischemic in jury include the cerebral cortex, hippocampus, striatum, and thalamus as well as selected struc tures of the brainstem. Subcortical and periventri cular white matter also is vulnerable, especially in the premature infant. The severity and distribution of the neuropathologic lesions are dependent on several factors, including the nature and duration of the insult, the gestational age of the fetus or new- 834bral hemisphere. During recovery, radioactivity in the contralateral cerebral hemisphere was no longer ap parent, whereas in the ipsilateral hemisphere, the extent of calcium accumulation was mild in four of six at 1 h, moderate in three of six at 5 h, moderate to intense in six of seven and six of seven at 24 and 72 h, respectively, and intense in three of three and two of two animals at 7 and 15 days, respectively. As during hypoxia-ischemia, the distribution of the radioactivity was most prominent in those structures that are known to be vulnerable to hyp oxic-ischemic injury. Thus, hypoxia-ischemia is asso ciated with enhanced calcium uptake into the immature brain, which does not dissipate but rather progressively accumulates for up to 15 days of recovery. The findings implicate a disruption of intracellular calcium homeo stasis as a major factor in the evolution of perinatal hyp oxic-ischemic brain damage. Key Words: Calcium Perinatal-Hypoxia-ischemia-Brain damage.born infant, and the presence or absence of super imposed systemic stress, e. g. , hypoglycemia, sepsis, or undernutrition (Vannucci and Plum, 1975). Vascular and metabolic factors (intrinsic vul nerability) also play a critical role as is known to exist in adults (Brierley and Graham, 1984).The underlying pathogenetic mechanism(s) re sponsible for the brain damaging...

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