Nimodipine Improves Outcome when Given after Complete Cerebral Ischemia in Primates

Steen, Petter Andreas; Gisvold, Sven Erik; Milde, James H.; Newberg, Leslie A.; Scheithauer, Bernd W.; Lanier, William L.; Michenfelder, John D.

doi:10.1097/00000542-198504000-00007

Cited by 255 publications

(56 citation statements)

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“…The failure of nitrendipine to protect against glutamate neurotoxicity would suggest that L-type calcium channels are not involved in the evolution of this insult under the present experimental conditions, although a report by Weiss et al (1990) shown to reduce the neuronal damage produced by cerebral ischaemia in animal models. These agents include NMDA antagonists (Park et al, 1988;Gill et al, 1991), non-NMDA excitatory amino acid receptor antagonists (Sheardown et al, 1990;but see DeGraba et al, 1994), calcium and sodium channel inhibitors (Steen et al, 1985;Alps et al, 1988;Pauwels et al, 1991) and inhibitors of lipid peroxidation (Hall et al, 1988;Young et al, 1988 cultures. The anticonvulsant agent and sodium channel inhibitor, phenytoin, has been shown to enhance recovery of synaptic transmission in rat hippocampal slices under conditions of simulated ischaemia (Kenny & Sheridan, 1992).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective profile of lifarizine (RS‐87476) in rat cerebrocortical neurones in culture

May¹,

Rowand²,

McCormack³

et al. 1995

British J Pharmacology

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1 The ability of the neuroprotective agent, lifarizine (RS‐87476), to mitigate veratridine‐, cyanide‐ and glutamate‐induced toxicity in rat embryonic cerebrocortical neurones in primary culture has been compared with that of tetrodotoxin (TTX), nitrendipine, (+)‐MK‐801 and (−)‐MK‐801. Lactate dehydrogenase (LDH) released into the culture medium was used as the indicator of cell viability.2 Incubation of cultures for 16 h in a medium containing veratridine (10−4 M), sodium glutamate (10−3M) or sodium cyanide (10−3M) resulted in consistent elevations of LDH activity in the culture medium. The ability of compounds to attenuate these elevations was expressed as the concentration required to inhibit the increases in LDH release by 50% (IC50).3 Neurotoxicity induced by veratridine was inhibited by lifarizine (IC50 = 4× 10−7M), TTX (IC50 = 3 × 10−8 M) and nitrendipine (IC50 = 3 × 10−5 M). In contrast, (+)‐MK‐801 (up to 3 × 10−5 M) was ineffective against this insult.4 Glutamate‐induced neurotoxicity was inhibited by (+)‐MK‐801 (IC50 = 1.4 × 10 −8 M) and to a lesser extent by (−)‐MK‐801 (IC50 = 1 × 10−7 M), but was unaffected by lifarizine, TTX or nitrendipine (up to 10−6M).5 (+)‐MK‐801 was effective against sodium cyanide‐induced neurotoxicity (IC50= 1.9 × 10−8M), whereas lifarizine and TTX (up to 10−6 m) and nitrendipine (up to 3 × 10−6 m) were without protective activity against this insult.6 The results demonstrate that lifarizine potently protects rat cortical neurones in vitro against a neurotoxic insult that requires activation of sodium channels for its expression, and that the compound is ineffective against insults mediated by N‐methyl‐D‐aspartate receptor activation. The weak efficacy of nitrendipine against veratridine‐induced cell death argues against the involvement of L‐type calcium channels in this insult. These data are consistent with the notion that the neuroprotective activity of lifarizine observed in vivo may be mediated by inhibition of neuronal sodium currents.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective profile of lifarizine (RS‐87476) in rat cerebrocortical neurones in culture

May¹,

Rowand²,

McCormack³

et al. 1995

British J Pharmacology

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“…~8 These doses have also been shown to improve neurological outcome following cerebral ischaemia in animals. 6 The lack of a discrete dose-response relationship in the reduction of anaesthetic requirement by nimodipine probably reflects the relative insensitivity of MAC measurement in discriminating small changes in anaesthetic potency. This may also indicate a nonspecific, nonreceptor-mediated action of nimodipine on anaesthesia.…”

Section: Discussionmentioning

confidence: 99%

“…5 Furthermore, nimodipine has been shown to improve neurologic outcome following complete cerebral ischaemia in primates. 6 Since nimodipine is frequently administered to patients undergoing anaesthesia and surgery for intracranial aneurysms, this study was designed to determine if nimodipine alters the anaesthetic effect of isoflurane in dogs.…”

Section: 0 Izgkg-tmin-i) Chez Cinq Chiens Nous Avons Aussi Mesumentioning

confidence: 99%

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs

et al. 1991

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“…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). This hypoperfusion may be re lated to calcium-induced cerebral vasospasm, in creased blood viscosity and/or platelet aggregation (Mohamed et aI., 1985;Steen et a!., 1985). Thus, altered calcium homeostasis may represent the "final common pathway" not only for hypoxia ischemia but for other forms of acute brain damage as well (Siesj6, 1981).…”

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confidence: 99%

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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Nimodipine Improves Outcome when Given after Complete Cerebral Ischemia in Primates

Cited by 255 publications

References 0 publications

Neuroprotective profile of lifarizine (RS‐87476) in rat cerebrocortical neurones in culture

Neuroprotective profile of lifarizine (RS‐87476) in rat cerebrocortical neurones in culture

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs

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

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