Effects of Hypothermia or Anesthetics on Hippocampal Glutamate and Glycine Concentrations after Repeated Transient Global Cerebral Ischemia

Illievich, U. M.; Zornow, Mark H.; Choi, Kyu Taek; Strnat, Martin A. P.; Scheller, Mark S.

doi:10.1097/00000542-199401000-00025

Cited by 98 publications

(33 citation statements)

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“…Glutamate receptor antagonists reduce neurological and histopathological indices of ischemic injury in brain (Meldrum et al, 1987;Newell et al, 1995) and spinal cord (Faden et al, 1990), a finding consistent with the observation that ischemia /anoxia increases excitatory amino acid release from brain (Busto et al, 1989) and spinal cord (Marsala et al, 1994a). Recent work has shown that this glutamate release after ischemia is exquisitely sensitive to modest reductions in local brain (Illievich et al, 1994) or spinal temperature (Marsala et al, 1994b). These data suggest a covariance between the effects of hypothermia on ischemia-induced injury and transmitter release (vs an effect mediated solely by suppression of CMRO 2 ).…”

Section: Abstract: Hypothermia; Hyperthermia; Glutamate; Cgrp; Spinasupporting

confidence: 53%

Temperature Dependency of Basal and Evoked Release of Amino Acids and Calcitonin Gene-Related Peptide from Rat Dorsal Spinal Cord

1997

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Moderate hypothermia significantly diminishes consequences of spinal and cerebral anoxia. One component of this neuroprotection has been hypothesized to be suppression of excitotoxic transmitter release. Whether this suppression is attributable to reduced hypoxic injury that induces release or an alteration of the release process itself is unclear. We sought to characterize the temperature sensitivity (Q 10 ) of basal and evoked calcitonin gene-related peptide (CGRP) and amino acid release from dorsal horn slices of rat spinal cord over a range of temperatures from 40 to 8°C. At 40°C, potassium (60 mM) and capsaicin (10 M) evoked a 21-and 32-fold increase in basal CGRP concentrations, respectively. Capsaicin had no effect on glutamate release, but potassium evoked a 2.7-fold increase. Release evoked by either potassium or capsaicin was reduced in a biphasic fashion with declining temperature. Over the range of 40 to 34°C, the Q 10 values for evoked release for CGRP were 11.3 (potassium) and 39.7 (capsaicin) and for glutamate, 5.5 (potassium). Over the range of 34 to 8°C, Q 10 values were near unity for all evoked release (0.8 and 1.3 for CGRP and 1.2 for glutamate). Although serine, glycine, glutamine, taurine, and citrulline showed no evoked release, basal levels were reduced at temperatures below 34°C. The pronounced temperature dependency of evoked transmitter release between 40 and 34°C is consistent with the profound cerebral protection observed with mild hypothermia in which metabolic activity is only slightly depressed. Key words: hypothermia; hyperthermia; glutamate; CGRP; spinal cord superfusion; evoked transmitter release; dorsal horn; capsaicinReduction of brain or spinal temperature by 3-5°C has been shown in preclinical and clinical models to attenuate neuronal damage and dysfunction after ischemia (Vacanti and Ames, 1984;Busto et al., 1989). Several mechanisms have been proposed to account for the protection produced by such hypothermia. The first assumes that ischemic injury occurs secondary to depletion of metabolic stores and that hypothermia preserves these stores by reducing cerebral metabolic rate of oxygen consumption (CMRO 2 ). In animal models of cerebral ischemia, CMRO 2 declines monotonically by ϳ4.5% per degree over the range of 37-38°C (normothermia) to 15-18°C (profound hypothermia) (Michenfelder and Milde, 1992). These findings are clinically relevant, because recovery of normal function in humans can be observed after 60 min of circulatory arrest when the arrest occurs at 15-18°C (Tharion et al., 1982). Although such profound hypothermia has been widely acknowledged, considerable data suggest that a surprisingly moderate hypothermia (32-34°C) can provide neurological protection in the face of cerebral and spinal ischemia. Such a modest reduction in tissue temperature has little effect on CMRO 2 and does not preserve metabolic stores (Hagerdal et al., 1975;Sano et al., 1992).A second mechanism that may underlie hypothermic neuroprotection involves excitotoxicity. Activation of NMDA a...

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Section: Abstract: Hypothermia; Hyperthermia; Glutamate; Cgrp; Spinasupporting

confidence: 53%

Temperature Dependency of Basal and Evoked Release of Amino Acids and Calcitonin Gene-Related Peptide from Rat Dorsal Spinal Cord

1997

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“…Hypothermia is known to reduce glutamate release, 42 which would be expected to reduce excitotoxic apoptosis. 43,44 Hypothermia also reduces glycine release, and this may further reduce hyperexcitation, as glycine promotes the effect of glutamate on NMDA receptors. Furthermore, activation of the Akt/protein kinase B pathway is known to be neuroprotective, and hypothermia may protect against ischemic damage by preserving Akt activity, which in turn inhibits some proapoptotic proteins.…”

Section: Discussionmentioning

confidence: 99%

Xenon and Hypothermia Combine Additively, Offering Long-Term Functional and Histopathologic Neuroprotection After Neonatal Hypoxia/Ischemia

Hobbs

Thoresen

Tucker

et al. 2008

Stroke

214

219

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Background and Purpose-Hypoxic/ischemic (HI) brain injury affects 1 to 6 per 1000 live human births, with a mortality of 15% to 20%. A quarter of survivors have permanent disabilities. Hypothermia is the only intervention that improves outcome; however, further improvements might be obtained by combining hypothermia with additional treatments. Xenon is a noble anesthetic gas with an excellent safety profile, showing great promise in vitro and in vivo as a neuroprotectant. We investigated combinations of 50% xenon (Xe 50% ) and hypothermia of 32°C (HT 32°C ) as a post-HI therapy. Methods-An established neonatal rat HI model was used. Serial functional neurologic testing into adulthood 10 weeks after injury was performed, followed by global and regional brain histopathology evaluation. Results-In the combination Xe 50% HT 32°C group, complete restoration of long-term functional outcomes was seen.Hypothermia produced improvement on short-(PϽ0.001) and long-(PϽ0.001) term functional testing, whereas Xe 50% alone predominantly improved long-term function (PϽ0.05), suggesting that short-term testing does not always predict eventual outcome. Similarly, the Xe 50% HT 32°C combination produced the greatest (71%) improvement in global histopathology scores, a pattern mirrored in the regional scores, whereas Xe 50% and HT 32°C individually produced smaller improvements (PϽ0.05 and PϽ0.001, respectively). The interaction between the 2 treatments was additive. Conclusions-The xenon/hypothermia combination additively confers greater protection after HI than either treatment alone. The functional improvement is almost complete, is sustained long term, and is accompanied by greatly improved histopathology. The unique safety profile differentiates xenon as an attractive combination therapy with hypothermia to improve the otherwise bleak outcome from neonatal HI.

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“…Glycine, an important facilitator of glutamate's action on the NMDA receptor, also is present in elevated concentrations after global ischaemia [1]. Decreases in temperature are known to inhibit the biosynthesis, release and uptake of various neurotransmitters [6,20]. Small decreases in brain temperature, therefore, may alter neurotransmitter release during ischaemia and through such a mechanism affect the outcome of the ischaemic insult [6].…”

Section: Failure Of Mild Hypothermiamentioning

confidence: 99%

Mild hypothermia fails to protect late hippocampal neuronal loss following forebrain cerebral ischaemia in rats

Taşdemiroğlu

1996

Acta neurochir

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Anaesthetized male rats (n = 86) from both Long-Evans strain (LES) (n = 43) and Wistar strain (WS) (n = 43) were utilized for the experiments. While three animals from each strain were used as control, 40 rats from each strain underwent up to 10 minutes forebrain ischaemia by bilateral common carotid artery (CCA) occlusion combined with systemic hypotension [Mean Arterial Blood Pressure (MABP) = 50 mm/Hg]. The animals from each strain were divided into four (n = 10) groups. In both strains, groups (n = 10) 1 and 2, temporalis muscle (TM) and body temperatures of the animals were kept at 36-37 degrees C during the experiments. The groups 1 and 2 were killed in 3 and 7 days after the ischaemic insult, respectively. The groups 3 and 4 were also killed 3 and 7 days after the ischaemic insult, but the forebrain ischaemia was carried out under mild cerebral hypothermia (TM temperature = 33 degrees C). Pyramidal neurons of the hippocampal CA1 region from each group was evaluated semiquantitatively. In WS, groups 1 and 2 showed moderate and severe neuronal loss in the CA1 region, respectively. However, in LES while the group 1 (3 days survival) did not show any neuronal loss, group 2 showed moderate neuronal loss of the CA1 region. While in group 3 (3 days survival, hypothermia) WS and LES, hypothermia protected the CA1 region, group 4 of LES showed mild neuronal loss. However WS, group 4 (7 days survival, hypothermia) showed severe neuronal loss of the CA1 region. It was concluded that mild hypothermia during ischaemic insults did not prevent the delayed postischaemic neuronal damage of the hippocampal CA1 region of both strains, and following 10 minutes forebrain ischaemia, male LES rats were found more resistant than male WS rats to neuronal loss of the CA1 region.

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Effects of Hypothermia or Anesthetics on Hippocampal Glutamate and Glycine Concentrations after Repeated Transient Global Cerebral Ischemia

Cited by 98 publications

References 0 publications

Temperature Dependency of Basal and Evoked Release of Amino Acids and Calcitonin Gene-Related Peptide from Rat Dorsal Spinal Cord

Temperature Dependency of Basal and Evoked Release of Amino Acids and Calcitonin Gene-Related Peptide from Rat Dorsal Spinal Cord

Xenon and Hypothermia Combine Additively, Offering Long-Term Functional and Histopathologic Neuroprotection After Neonatal Hypoxia/Ischemia

Mild hypothermia fails to protect late hippocampal neuronal loss following forebrain cerebral ischaemia in rats

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