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Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain.

ABSTRACT: Occurrence of transient ischemic attacks (TIA) and cerebral strokes is a recognized risk associated with cocaine abuse. Here, we use a rodent model along with optical imaging to study cocaine-induced TIA and the associated dynamic changes in cerebral blood flow velocity (CBFv) and cerebrovasculature. We show that chronic cocaine exposure in mice resulted in marked cortical hypoperfusion, in significant arterial and venous vasoconstriction, and in a sensitized vascular response to an acute cocaine injection. Starting after 10 days of exposure, an acute cocaine challenge to these mice resulted in a TIA, which presented as hemiparalysis and was associated with an abrupt exacerbation of CBFv. The severity of the TIA correlated with the decreases in cortical CBFv such that the greater the decreases in flow, the longer the TIA duration. The severity of TIA peaked around 17-22 days of cocaine exposure and decreased thereafter in parallel to a reorganization of CBFv from superficial to deep cortical layers, along with an increase in vessel density into these layers. Here, we document for the first time to our knowledge evidence of a TIA in an animal model of chronic cocaine exposure that was associated with profound decreases in CBFv, and we revealed that while the severity of the TIA initially increased with repeated exposures, it subsequently improved in parallel to an increase in the vessel density. This suggests that strategies to accelerate cerebrovascular recovery might be therapeutically beneficial in cocaine abusers.

SUBMITTER: You J

PROVIDER: S-EPMC5333953 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBrain lesions on diffusion-weighted imaging (DWI) are frequently found after carotid artery stenting (CAS), but their clinical relevance remains unclear.ObjectivesThis study sought to investigate whether periprocedural ischemic DWI lesions after CAS or carotid endarterectomy (CEA) are associated with an increased risk of recurrent cerebrovascular events.MethodsIn the magnetic resonance imaging (MRI) substudy of ICSS (International Carotid Stenting Study), 231 patients with symptomatic carotid stenosis were randomized to undergo CAS (n=124) or CEA (n=107). MRIs were performed 1 to 7 days before and 1 to 3 days after treatment. The primary outcome event was stroke or transient ischemic attack in any territory occurring between the post-treatment MRI and the end of follow-up. Time to occurrence of the primary outcome event was compared between patients with (DWI+) and without (DWI-) new DWI lesions on the post-treatment scan in the CAS and CEA groups separately.ResultsMedian time of follow-up was 4.1 years (interquartile range: 3.0 to 5.2). In the CAS group, recurrent stroke or transient ischemic attack occurred more often among DWI+ patients (12 of 62) than among DWI- patients (6 of 62), with a cumulative 5-year incidence of 22.8% (standard error [SE]: 7.1%) and 8.8% (SE: 3.8%), respectively (unadjusted hazard ratio: 2.85; 95% confidence interval: 1.05 to 7.72; p=0.04). In DWI+ and DWI- patients, 8 and 2 events, respectively, occurred within 6 months after treatment. In the CEA group, there was no difference in recurrent cerebrovascular events between DWI+ and DWI- patients.ConclusionsIschemic brain lesions discovered on DWI after CAS seem to be a marker of increased risk for recurrent cerebrovascular events. Patients with periprocedural DWI lesions might benefit from more aggressive and prolonged antiplatelet therapy after CAS. (A Randomised Comparison of the Risks, Benefits and Cost Effectiveness of Primary Carotid Stenting With Carotid Endarterectomy: International Carotid Stenting Study; ISRCTN25337470).

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Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain.

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