Demonstration of Dose-Dependent Global and Regional Cocaine-Induced Reductions in Brain Blood Flow Using a Novel Approach to Quantitative Single Photon Emission Computerized Tomography

Johnson, Bankole A.

doi:10.1016/s0893-133x(97)00168-1

Cited by 39 publications

(8 citation statements)

References 21 publications

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“…Using specific examples for selected drugs, a large bolus of cocaine (0.5 mg/kg) decreases CBF in human basal ganglia by 20–30% (Wallace et al, 1996, Johnson et al, 1998), and a similar dose decreases cerebral blood volume (CBV) in the basal ganglia of non-human primates by 10–15% (Mandeville et al, 2011), values which are concordant with the human data when using the commonly applied power-law relationship between CBF and CBV (Grubb et al, 1973). In rodent models, even very large doses of psycho-stimulants produce changes in CBV that rarely exceed 20% in magnitude (Jenkins, 2012).…”

Section: Data Acquisitionsupporting

confidence: 57%

Data collection and analysis strategies for phMRI

Mandeville¹,

Liu²,

Vanduffel³

et al. 2014

Neuropharmacology

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Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed “phMRI”. The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners.

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Section: Data Acquisitionsupporting

confidence: 57%

Data collection and analysis strategies for phMRI

Mandeville¹,

Liu²,

Vanduffel³

et al. 2014

Neuropharmacology

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“…Johnson et al, using novel quantitative single photon emission CT method for measuring brain blood flow, demonstrated that intravenous cocaine use is associated with a global reduction in brain blood flow. However, the reduction in blood flow was more pronounced in the dopamine-rich regions of the brain such as prefrontal, frontal, temporal and subcortical gray matter [ 17 ]. We hypothesize that posterior inferior cerebellar artery, posterior cerebral arteries, and lenticulostriate arteries are selectively prone to transient vasospasm due to the high adrenergic state from increased circulating catecholamines affecting their autoregulation.…”

Section: Discussionmentioning

confidence: 99%

Cocaine Induced Bilateral Posterior Inferior Cerebellar Artery and Hippocampal Infarction

Mullaguri

Battineni

Narayan

et al. 2018

Cureus

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Cocaine is one of the most commonly abused recreational drugs, second only to marijuana. It blocks the reuptake of neurotransmitters such as norepinephrine and dopamine, that leads to persistent post-synaptic stimulation responsible for its excitatory effects. Cocaine-related strokes, both ischemic and hemorrhagic, have been well described in the literature and cerebral vasospasm is hypothesized as one of the major mechanisms responsible for the presentation. Although cases of posterior circulation infarction were previously reported, we herein report a rare presentation of a cocaine-induced bilateral posterior inferior cerebellar artery and hippocampal infarction in a middle-aged female.

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“…Even though the mechanism of cocaine-related TIA and stroke are not completely understood, it is generally accepted that cocaine-induced vasoconstriction is a key contributing factor [2]. The effects of cocaine in various brain regions differ, not only because it causes increases in dopamine release and metabolism [3], but also due to cocaine-induced cerebral vasospasm, which appears to be most prominent in frontal cortical regions including prefrontal cortex and somatosensory cortex [4], where cerebral blood flow is most affected [5, 6]. Indeed, using contrast-enhanced ultrahigh-resolution optical coherence tomography, we recently showed that single or repeated cocaine administration to the mouse somatosensory cortex induced cerebral micro-ischemia [7].…”

Section: Introductionmentioning

confidence: 99%

Chronic cocaine induces HIF-VEGF pathway activation along with angiogenesis in the brain

et al. 2017

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Cocaine induces vasoconstriction in cerebral vessels, which with repeated use can result in transient ischemic attacks and cerebral strokes. However, the neuroadaptations that follow cocaine’s vasoconstricting effects are not well understood. Here, we investigated the effects of chronic cocaine exposure (2 and 4 weeks) on markers of vascular function and morphology in the rat brain. For this purpose we measured nitric oxide (NO) concentration in plasma, brain neuronal nitric oxide synthase (nNOS or NOS1), HIF-1α, and VEGF expression in different brain regions, i.e., middle prefrontal cortex, somatosensory cortex, nucleus accumbens, and dorsal striatum, using ELISA or Western blot. Additionally, microvascular density in these brain regions was measured using immunofluorescence microscopy. We showed that chronic cocaine significantly affected NOS1, HIF-1α and VEGF expression, in a region- and cocaine treatment-time- dependent manner. Cerebral microvascular density increased significantly in parallel to these neurochemical changes. Furthermore, significant correlations were detected between VEGF expression and microvascular density in cortical regions (middle prefrontal cortex and somatosensory cortex), but not in striatal regions (nucleus accumbens and dorsal striatum). These results suggest that following chronic cocaine use, as cerebral ischemia developed, NOS1, the regulatory protein to counteract blood vessel constriction, was upregulated; meanwhile, the HIF-VEGF pathway was activated to increase microvascular density (i.e., angiogenesis) and thus restore local blood flow and oxygen supply. These physiological responses were triggered presumably as an adaptation to minimize ischemic injury caused by cocaine. Therefore, effectively promoting such physiological responses may provide novel and effective therapeutic solutions to treat cocaine-induced cerebral ischemia and stroke.

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Demonstration of Dose-Dependent Global and Regional Cocaine-Induced Reductions in Brain Blood Flow Using a Novel Approach to Quantitative Single Photon Emission Computerized Tomography

Abstract: Ischemic stroke is a common cause of morbidity and mortality in cocaine addicts

Cited by 39 publications

References 21 publications

Data collection and analysis strategies for phMRI

Data collection and analysis strategies for phMRI

Cocaine Induced Bilateral Posterior Inferior Cerebellar Artery and Hippocampal Infarction

Chronic cocaine induces HIF-VEGF pathway activation along with angiogenesis in the brain

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