Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects

Du, Congwu; Yu, Mei; Volkow, Nora D.; Koretsky, Alan P.; Fowler, Joanna S.; Benveniste, Helene

doi:10.1523/jneurosci.3612-06.2006

Cited by 62 publications

(55 citation statements)

References 67 publications

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“…To assess cellular oscillations, we measured LFOs of Ca 2+ i fluorescence using the calcium indicator Rhod 2 -AM locally microinjected into the somatosensory cortex (27). The LFO power spectra of CBFv, HbO 2 , and HbR within the Rhod 2 -loaded tissue area were almost identical to those in surrounding areas without Rhod 2 loading (SI Appendix, Fig.…”

Section: Ca 2+ I Fluctuates Within a Frequency Band Similar To That Omentioning

confidence: 95%

“…1E and Fig. 5, 6 of the 10 rats received microinfusion of the Ca 2+ i indicator Rhod 2 -AM (100μM, 3 μL/min; Molecular Probes) locally in the cortex (27) before the dura was removed, whereas other the 4 rats were used to assess effect of PCO 2 on vascular dilation and to measure local field potentials (LFP) for assessing changes in neuronal activity from normocapnia to hypercapnia. Hemodynamic parameters were compared between an ROI near the Rhod 2 injection spot (red circle and red curves) and a distant ROI (light blue circle and light blue curves) as shown in SI Appendix, Fig.…”

Section: Methodsmentioning

confidence: 99%

“…SR101 (28) has excitation (λ 1 ) and emission (λ em ) wavelengths similar to those of Rhod 2 (27) but provides information on cell morphology instead of cellular activity, as is the case for the Ca 2+ i changes with Rhod 2 . SI Appendix, (Fig.…”

Section: Ca 2+ I Fluctuates Within a Frequency Band Similar To That Omentioning

confidence: 99%

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Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex

Volkow

Koretsky

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Spontaneous low-frequency oscillations (LFOs) of blood-oxygenlevel-dependent (BOLD) signals are used to map brain functional connectivity with functional MRI, but their source is not well understood. Here we used optical imaging to assess whether LFOs from vascular signals covary with oscillatory intracellular calcium (Ca 2+ i ) and with local field potentials in the rat's somatosensory cortex. We observed that the frequency of Ca 2+ i oscillations in tissue (∼0.07 Hz) was similar to the LFOs of deoxyhemoglobin (HbR) and oxyhemoglobin (HbO 2 ) in both large blood vessels and capillaries. The HbR and HbO 2 fluctuations within tissue correlated with Ca 2+ i oscillations with a lag time of ∼5-6 s. The Ca 2+ i and hemoglobin oscillations were insensitive to hypercapnia. In contrast, cerebral-blood-flow velocity (CBFv) in arteries and veins fluctuated at a higher frequency (∼0.12 Hz) and was sensitive to hypercapnia. However, in parenchymal tissue, CBFv oscillated with peaks at both ∼0.06 Hz and ∼0.12 Hz. Although the higher-frequency CBFv oscillation (∼0.12 Hz) was decreased by hypercapnia, its lower-frequency component (∼0.06 Hz) was not. The sensitivity of the higher CBF V oscillations to hypercapnia, which triggers blood vessel vasodilation, suggests its dependence on vascular effects that are distinct from the LFOs detected in HbR, HbO 2 , Ca 2+ i , and the lower-frequency tissue CBFv, which were insensitive to hypercapnia. Hemodynamic LFOs correlated both with Ca 2+ i and neuronal firing (local field potentials), indicating that they directly reflect neuronal activity (perhaps also glial). These findings show that HbR fluctuations (basis of BOLD oscillations) are linked to oscillatory cellular activity and detectable throughout the vascular tree (arteries, capillaries, and veins).spontaneous low-frequency brain oscillations | resting-state functional connectivity | neuronal calcium | cerebral hemodynamic | neuroimaging M easures of resting-state functional connectivity with functional MRI (fMRI) are based on spontaneous low-frequency blood-oxygen-level-dependent (BOLD) oscillations that occur throughout the brain with the assumption that regions with correlated oscillations are functionally connected (1, 2). The networks that emerge from resting-state functional connectivity correspond roughly with neuroanatomical connectivity (3, 4) and are modified by brain diseases (5-7). BOLD signals in fMRI reflect the interplay between hemodynamics (including blood volume and velocity of blood flowing in the vessels) and cellular (neuronal and glial) metabolism, which affect the amount of deoxygenated hemoglobin (HbR) in brain tissue that leads to changes in BOLD fMRI (8,9). Human studies using near-infrared spectroscopy (NIRS) (10) have reported low-frequency oscillations (LFOs) of ∼0.04-0.1 Hz for oxygenated hemoglobin (HbO 2 ) and HbR in the brain consistent with those measured by BOLD (11). However, there is still no quantitative understanding of the relative direct contribution of spontaneous oscillations in cellular...

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Section: Ca 2+ I Fluctuates Within a Frequency Band Similar To That Omentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex

Volkow

Koretsky

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…It causes vasoconstriction due to its potent sympathomimetic properties. It prevents the reuptake of noradrenaline, serotonin, and dopamine at presynaptic nerve terminals and increases the release of calcium from the sarcoplasmic reticulum in cerebral vascular smooth muscle cells, resulting in vasoconstriction [5,6]. Endothelin-1 is another important mediator of cocaine-induced cerebral vasospasm [7].…”

Section: Discussionmentioning

confidence: 99%

Neurotoxic and cardiotoxic effects of cocaine and ethanol

2009

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Introduction: Concurrent abuse of alcohol and cocaine results in the formation of cocaethylene, a powerful cocaine metabolite. Cocaethylene potentiates the direct cardiotoxic and indirect neurotoxic effects of cocaine or alcohol alone.Case Report: A 44-year-old female with history of cocaine and alcohol abuse presented with massive stroke in the emergency department. CT scan revealed extensive left internal carotid artery dissection extending into the left middle and anterior cerebral arteries resulting in a massive left hemispheric infarct, requiring urgent decompressive craniectomy. The patient had a stormy hospital course with multiple episodes of torsades de pointes in the first 4 days requiring aggressive management. She survived all events and was discharged to a nursing home with residual right hemiplegia and aphasia.Conclusion: The combination of ethanol and cocaine has been associated with a significant increase in the incidence of neurological and cardiac emergencies including cerebral infarction, intracranial hemorrhage, myocardial infarction, cardiomyopathy, and cardiac arrhythmias. The alteration of cocaine pharmacokinetics and the formation of cocaethylene have been implicated, at least partially, in the increased toxicity of this drug combination.

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“…Effects may be transient or permanent and occur as a result of decreases in mean arterial blood pressure, glucose utilization, blood volume, tissue oxygenation, and cerebral blood flow due to vasoconstriction in addition to an independent increase in intracellular calcium concentration associated with cell death. 9 Conversely, therapeutic hypothermia has long been believed to be capable of reducing primary brain injury and preventing secondary inury, 10 and its use even in stroke patients is an area of ongoing study and scientific interest without definitive conclusions. 11 Therapeutic hypothermia is theorized to combat global ischemia in several unique ways.…”

Section: Case Reportmentioning

confidence: 99%

Use of Therapeutic Hypothermia in Cocaine-Induced Cardiac Arrest: Further Evidence

Scantling

Klonoski

Valentino

2014

American Journal of Critical Care

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Therapeutic hypothermia is an important and successful treatment that has been endorsed only in specific clinical settings of cardiac arrest. Inclusion criteria thus far have not embraced drug-induced cardiac arrest, but clinical evidence has been mounting that therapeutic hypothermia may be beneficial in such cases. A 59-year-old man who experienced a cocaine-induced cardiac arrest had a full neurological recovery after use of therapeutic hypothermia. The relevant pathophysiology of cocaine-induced cardiac arrest is reviewed, the mechanism and history of therapeutic hypothermia are discussed, and the clinical evidence recommending the use of therapeutic hypothermia in cocaineinduced cardiac arrest is reinforced. (American Journal of Critical Care. 2014; 23:89-92) T herapeutic hypothermia remains a relatively new immediate treatment option for patients who have had return of spontaneous circulation after cardiac arrest but remain unresponsive. In several studies, 1 therapeutic hypothermia has been definitively shown to improve neurological recovery when used after the return of spontaneous circulation. These studies, however, excluded survivors of drug-induced cardiac arrest.2 As a result, evidence supporting the use of therapeutic hypothermia in drug-induced cardiac arrest has been absent despite clinical suspicion of its benefits. We report a second unique published instance of successful use of therapeutic hypothermia in the setting of cocaine-induced cardiac arrest.

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Cocaine Increases the Intracellular Calcium Concentration in Brain Independently of Its Cerebrovascular Effects

Cited by 62 publications

References 67 publications

Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex

Low-frequency calcium oscillations accompany deoxyhemoglobin oscillations in rat somatosensory cortex

Neurotoxic and cardiotoxic effects of cocaine and ethanol

Use of Therapeutic Hypothermia in Cocaine-Induced Cardiac Arrest: Further Evidence

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