Calcium, Excitotoxins, and Neuronal Death in the Brain<sup>a</sup>

Siesjö, Bo K.; Bengtsson, Finn; Grampp, W.; Theander, Sten

doi:10.1111/j.1749-6632.1989.tb12513.x

Cited by 223 publications

(84 citation statements)

References 91 publications

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“…Most important, our data are consistent with the "calcium homeostasis" or "setpoint" hypothesis for neuronal survival proposed by these authors (Koike et al, 1989;Koike and Tanaka, 1991), which is comparable with one proposed earlier for growth cone stability (Kater et al, 1988 (Choi, 1988;Siesjo et al, 1989). This is of particular consequence for auditory neurons that have high levels of spontaneous and even higher levels of evoked activity, which could compromise survival through increased Ca 2ϩ influx.…”

Section: Additivity Can Account For the Requirement For Multiple Soursupporting

confidence: 92%

“…The neurotrophic effect of depolarization is apparently a consequence of a sustained rise in cytosolic Ca 2ϩ , entering through L-type Ca 2ϩ channels (Gallo et al, 1987;Collins and Lile, 1989;Koike et al, 1989;Collins et al, 1991). This is in spite of the critical role of cytosolic Ca 2ϩ in mediating neuronal degeneration (Choi, 1988;Siesjo et al, 1989). A hypothesis unifying these observations proposes that [Ca 2ϩ ] i must rise to a particular "setpoint" to promote survival in the absence of neurotrophic factor; degeneration is the result of very high [Ca 2ϩ ] i (Collins et al, 1991;Koike and Tanaka, 1991;Franklin and Johnson, 1992).…”

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confidence: 99%

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Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_iwithin a Set Range

Kay²,

1997

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Section: Additivity Can Account For the Requirement For Multiple Soursupporting

confidence: 92%

mentioning

confidence: 99%

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_iwithin a Set Range

Kay²,

1997

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“…This high concentration of calcium leads to release of excitatory neurotransmitter glutamate into the extracellular space. Excess glutamate triggers the excitotoxic cascade that can ultimately result in cell injury and death [39]. Even mild decreases in temperature have been shown to ameliorate these detrimental effects [40][41][42].…”

Section: Detrimental Effects Of Fevermentioning

confidence: 99%

Therapeutic Hypothermia for Acute Neurological Injuries

2012

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Therapeutic hypothermia (TH) is the intentional reduction of core body temperature to 32°C to 35°C, and is increasingly applied by intensivists for a variety of acute neurological injuries to achieve neuroprotection and reduction of elevated intracranial pressure. TH improves outcomes in comatose patients after a cardiac arrest with a shockable rhythm, but other off-label applications exist and are likely to increase in the future. This comprehensive review summarizes the physiology and cellular mechanism of action of TH, as well as different means of TH induction and maintenance with potential side effects. Indications of TH are critically reviewed by disease entity, as reported in the most recent literature, and evidence-based recommendations are provided.

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“…Within two minutes without blood flow, neurons lack the energy to power the Na + /K + pump, leading to loss of cellular gradients; thus, potassium ions move out of the cells while sodium and chloride ions rush inward [9]. During ischemia, neurons attempt to produce ATP by anaerobic glycolysis, and ATP breakdown leads to an increase in inorganic phosphate, lactate and H + formation, resulting cellular acidification [13].The loss of ATP and acidosis prevent sequestration of Ca 2+ from the cell, further aggravating intracellular Ca 2+ overload [14]. Depolarization of presynaptic membranes results in the release of massive amounts of the excitatory neurotransmitter glutamate (glutamic acid).…”

Section: Ischemic Neuronal Injurymentioning

confidence: 99%

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

Miclescu¹

2010

Acta Anaesthesiol Scand

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Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in "the field." Based on findings that MBL cardio-and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available. Keywords: Cardiac arrest, cardiopulmonary resuscitation, reperfusion injury, methylene blue, nitric oxide, nitric oxide synthases, blood-brain barrier

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Calcium, Excitotoxins, and Neuronal Death in the Brain^a

Cited by 223 publications

References 91 publications

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_iwithin a Set Range

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_iwithin a Set Range

Therapeutic Hypothermia for Acute Neurological Injuries

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

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Calcium, Excitotoxins, and Neuronal Death in the Braina

Cited by 223 publications

References 91 publications

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca2+]iwithin a Set Range

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca2+]iwithin a Set Range

Therapeutic Hypothermia for Acute Neurological Injuries

Cerebral protection in experimental cardiopulmonary resuscitation (with special reference to the effects of methylene blue)

Contact Info

Product

Resources

About

Calcium, Excitotoxins, and Neuronal Death in the Brain^a

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_iwithin a Set Range

Trophic Support of Cultured Spiral Ganglion Neurons by Depolarization Exceeds and Is Additive with that by Neurotrophins or cAMP and Requires Elevation of [Ca²⁺]_iwithin a Set Range