The pathophysiology of brain ischemia

Summary: Focal ischemia was induced in 23 cats by oc cluding the left middle cerebral artery for 2 h. The animals were then divided into groups for unforced reperfusion of variable duration ranging from 2 to 48 h. Neurological ratings were obtained during both ischemia and reperfu sion. Following planned sacrifice the regional ATP con tent was assessed by means of a bioluminescence method showing spatial distribution and degree of ATP depletion. All the animals developed a neurologic deficit, with a median of 6 points on a disability scale of 0-10. After reopening of the middle cerebral artery, neurologic re covery was quite variable depending on the initial neu rologic deficit (partial

Section: Discussionmentioning

confidence: 95%

Neurologic Deficit and Cerebral ATP Depletion after Temporary Focal Ischemia in Cats

Satō¹,

Paschen²,

Pawlik³

et al. 1984

“…In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modi fied by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number oPH-PN 200-110 binding sites in the hippocampus ipsiIncreasing evidence points to the role of calcium in the pathophysiology of ischemic brain damage (Siesjo, 1981;Raichle, 1983; Simon et aI., 1984;Siesjo and Wieloch, 1985). Calcium is an essential …”

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confidence: 92%

“…Increasing evidence points to the role of calcium in the pathophysiology of ischemic brain damage (Siesjo, 1981;Raichle, 1983;Simon et aI., 1984;Siesjo and Wieloch, 1985). Calcium is an essential lateral to the side of carotid occlusion, accompanied by an increase in the dissociation constant value, whereas no changes in the kinetic parameters of the binding were observed in the other areas examined, i.e., the cortex and the striatum.…”

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confidence: 99%

L-Type Calcium Channels are Modified in Rat Hippocampus by Short-Term Experimental Ischemia

Magnoni

Govoni

Battaini

et al. 1988

Summary: Increasing evidence suggests a role for cal cium ions in the pathophysiology of ischemic brain damage. The major mechanism allowing calcium entry from the extracellular compartment is the opening of voltage-operated calcium channels. In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modi fied by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number oPH-PN 200-110 binding sites in the hippocampus ipsiIncreasing evidence points to the role of calcium in the pathophysiology of ischemic brain damage (Siesjo, 1981;Raichle, 1983; Simon et aI., 1984;Siesjo and Wieloch, 1985). Calcium is an essential

“…Experiments in adult animals suggest that hypoxia-ischemia ini tiates a cascade of metabolic events, arising from a failure of cellular oxidative processes (Siesjo, 1981; Rossmann, 1982;Raichle, 1983;Meyer et al , 1987). These events include a disequilibrium of transmembrane ion and fluid gradients, catabolic processes with ribosomal disaggregation, protein degradation, and the liberation of free fatty acids…”

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confidence: 99%

“…, 1987). An increase in cyto solic calcium, in turn, causes phospholipase activa tion with the accumulation of free fatty acids, futile cycling of ions across mitochondria, and subse quent uncoupling of oxidative phosphorylation (Siesj6, 198 1;Hossmann, 1982;Raichle, 1983). Fur thermore, during recovery from cerebral hypoxia ischemia in adult animals, there is a period of de layed hypoperfusion that contributes further to cell injury (Levy et aI., 1979;Kogure et a!., 1980;Pul sinelli et a!., 1982).…”

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confidence: 99%

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

Stein

Vannucci

1988

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...