Effects of GABAA receptor blockade on regional cerebral blood flow and blood–brain barrier disruption in focal cerebral ischemia

Z., Oak; Hunter, Christine; Liu, Xia; Chi, Youngchan; Weiss, Harvey R.

doi:10.1016/j.jns.2010.10.024

Cited by 21 publications

(13 citation statements)

References 33 publications

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“…[16] In preclinical models, the inhibition of GABA A receptors has been associated with increased regional cerebral blood flow and blood-brain barrier disruption in cerebral ischemia. [17] These data support the hypothesis that off-target inhibition of GABA A receptors by enzalutamide, especially in areas of the central nervous system (CNS) that are responsible for sympathetic tone, may lead to hypertension that exceeds cerebral vascular autoregulation and ultimately results in vasogenic edema. Furthermore, the blood-brain barrier disruption that occurs during this process may result in increased CNS concentrations of enzalutamide and, therefore, may accelerate the development of PRES.…”

Section: Discussionsupporting

confidence: 60%

Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer

Crona

Whang

2014

Invest New Drugs

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Summary Posterior reversible encephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by symptoms that can include seizure, headache, impaired vision and hypertension, and can be confirmed by magnetic resonance imaging. Numerous reports have emerged that describe PRES in cancer patients. The list of medications linked to PRES can include traditional cytotoxic chemotherapeutics (e.g., cisplatin, cyclophosphamide, and high-dose corticosteroids), newer agents that target the vascular endothelial growth factor pathway (e.g., bevacizumab, sunitinib, and pazopanib), and supportive care mediations (e.g., granulocyte colony stimulating factors and erythropoietin). We report, for the first time, a case of PRES that is secondary to treatment with enzalutamide, a potent androgen receptor antagonist used in the treatment of metastatic castration-resistant prostate cancer. Enzalutamide is approved for the treatment of both docetaxel-pretreated and chemotherapy-naïve metastatic castration-resistant prostate cancer. Enzalutamide has been previously linked to the increased risk of seizures. Clinicians should be aware that, in rare cases, patients treated with enzalutamide could potentially be at risk for PRES. If symptoms suggestive of PRES arise in patients receiving enzalutamide, the drug should be discontinued immediately and the diagnostic process should be initiated.

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Section: Discussionsupporting

confidence: 60%

Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer

Crona

Whang

2014

Invest New Drugs

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“…A recent study has shown increased CBF on SPECT in children with severe traumatic brain injury (TBI) who were imaged 3 years following trauma; they explained it on the basis of delayed brain maturation [52]. Hyperperfusion observed in CP children in the current study could also be related to delay in brain maturation or to a lag in the development of their brain function.…”

Section: Discussionmentioning

confidence: 45%

Cerebral Blood Flow and DTI metrics changes in children with cerebral palsy following therapy

Jain

Paliwal

Yadav

et al. 2015

J Pediatr Neuroradiol

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It is known that patients with chronic hypoxia have regional changes in their cerebral blood flow (CBF). The purpose of this study was to observe the CBF and diffusion tensor imaging (DTI) metrics changes in children with cerebral palsy (CP) at baseline and after 6 months of treatment. Thirty-eight children with cerebral diplegia (mean age = 6.4 yr) and twenty-one age/sex matched controls (mean age = 7.5 yr) were evaluated by the Gross Motor Function Classification System (GMFCS) scoring of motor disability and modified Ashworth scoring of spasticity. All subjects underwent pseudo-continuous arterial spin labeling (PCASL) and DTI, in addition to conventional magnetic resonance imaging (MRI). Significant increase in CBF values was observed in several grey and white matter regions (including areas of abnormal T2 hyperintensity in the periventricular white matter) in CP children as compared to controls based upon voxel-wise analysis. Low fractional anisotropy (FA) and high apparent diffusion coefficient (ADC) values were observed in these areas of high CBF, using a region of interest (ROI) based analysis. On follow-up study, CBF values were found to be significantly higher in two grey matter areas and lower in three white matter regions in comparison to baseline; however no significant changes in DTI indices were observed in these regions. CBF values are high in CP children as compared to controls and show alteration following therapy even when the DTI metrics remain unchanged. Arterial spin labeling (ASL) may be added to the advanced imaging protocol for studying brain plasticity in such children in future.

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“…MCA occlusion has been associated with BBB disruption [1,2]. The extent of disruption can vary depending on many factors such as methods of MCA occlusion, duration of occlusion, molecular size of tracers, anesthetic agents, blood pressure, species and gender.…”

Section: Discussionmentioning

confidence: 99%

“…One of the consequences of stroke is blood-brain barrier (BBB) disruption [1,2]. Cerebral ischemia causes release or modulation of substances or factors such as excitatory amino acid, Ca ++ , nitric oxide, inflammatory agents, and all other factors which may affect BBB [3,4,5,6].…”

Section: Introductionmentioning

confidence: 99%

Effects of Cannabinoid Receptor Agonist WIN 55,212-2 on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia in Rats

Barsoum²,

Grayson³

et al. 2012

Pharmacology

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This study was performed to investigate whether WIN 55,212-2 (WIN), a cannabinoid receptor agonist, could attenuate blood-brain barrier (BBB) disruption in focal cerebral ischemia in rats and whether the CB₁ receptor antagonist rimonabant could prevent this attenuation. A total of 0.3 or 1 mg/kg of WIN was injected intravenously before and after permanent middle cerebral artery (MCA) occlusion. Some animals were pretreated with rimonabant 2 mg/kg i.p. before receiving 0.3 mg/kg of WIN. At 1 h after MCA occlusion, BBB permeability was determined by measuring the transfer coefficient (K_i) of ¹⁴C-α-aminoisobutyric acid and the volume of dextran distribution. With MCA occlusion, K_i increased in the ischemic cortex (IC) in all of the experimental groups. However, the K_i of the IC of the WIN 0.3 and 1 mg/kg groups was lower (–46 and –42%, respectively, p < 0.05) than that of the control group. With rimonabant pretreatment, the K_i of the IC became higher (+88%, p < 0.05) than with WIN 0.3 mg/kg alone and similar to that of the control rats. The difference in the volume of dextran distribution between the IC and the contralateral cortex was significant in the control but not in the WIN-treated rats. With rimonabant pretreatment, however, the difference became significant. Our data demonstrated that WIN could attenuate BBB disruption in focal cerebral ischemia and this attenuation could be prevented with rimonabant. Our data suggest an involvement of CB₁ receptors in the regulation of BBB disruption in the early stage of stroke.

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Effects of GABAA receptor blockade on regional cerebral blood flow and blood–brain barrier disruption in focal cerebral ischemia

Cited by 21 publications

References 33 publications

Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer

Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer

Cerebral Blood Flow and DTI metrics changes in children with cerebral palsy following therapy

Effects of Cannabinoid Receptor Agonist WIN 55,212-2 on Blood-Brain Barrier Disruption in Focal Cerebral Ischemia in Rats

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