Endovascular treatment in proximal and intracranial carotid occlusion 9 hours after symptom onset.

INTRODUCTION: A debate is emerging over whether the treatment time window in acute stroke can be extended beyond 6 h if penumbral tissue can be identified. Treatment decisions are very difficult in cases of tandem proximal carotid occlusion with arterioarterial intracranial embolism. We enter this debate with the present report on a case of atherosclerotic proximal carotid occlusion and resulting periocclusional carotid T embolism that was successfully treated 9 h after symptom onset. METHODS: The case of a 68-year-old man with fluctuating symptoms of right-hemispheric stroke is presented (NIHSS score 12-20 on admission). CT angiography demonstrated proximal carotid occlusion and periocclusional embolism of the entire internal carotid artery (ICA) including the carotid T segment. Penumbral tissue was diagnosed by nonenhanced and perfusion CT imaging 7.5 h after symptom onset. Treatment was initiated 9 h after symptom onset by passing the proximal occlusion with a microcatheter and local administration of recombinant tissue plasminogen activator (rt-PA) into the carotid T segment at the level of posterior communicating artery (PCoA) origin. RESULTS: Recanalization of the ICA and middle cerebral artery was accomplished within 1 h by flow establishment via the PCoA. The atherosclerotic proximal ICA occlusion was not stented due to the risk of embolism from remnant thrombi in the petrous and cavernous ICA segments. Follow-up MRI showed only mild haemorrhagic infarct transformation of the initial infarct core. The patient was discharged from hospital 18 days after treatment with NIHSS score 5. CONCLUSION: If penumbral tissue can be conclusively identified, endovascular treatment in proximal and intracranial tandem occlusion can be successful, even in treatments initiated 6-9 h after stroke onset. If the intracranial flow after recanalization can be established via the circle of Willis, the underlying proximal ICA occlusion may not require treatment.

CREB binding to the hypoxia-inducible factor-1 responsive elements in the plasminogen activator inhibitor-1 promoter mediates the glucagon effect.

Plasminogen activator inhibitor-1 (PAI-1) controls the regulation of the fibrinolytic system in blood by inhibiting both urokinase-type and tissue-type plasminogen activators. Enhanced levels of PAI-1 are related to pathological conditions associated with hypoxia or hyperinsulinemia. In this study, we investigated the regulation of PAI-1 expression by glucagon and the cAMP/PKA/CREB signalling pathway in the liver. Stimulation of the cAMP/PKA/CREB signalling cascade by starvation in vivo or glucagon in vitro induced PAI-1 gene expression in liver. Furthermore, this response was associated with enhanced phosphorylation of CREB. By using EMSAs we found that three promoter elements, the HRE2, E-box 4 and E-box 5, were able to bind CREB but only the HRE2 and E5 appeared to be functionally active. Reporter gene assays confirmed that cAMP induced PAI-1 gene transcription via the same element in both human and rat promoters. Interestingly, although the HRE2 was involved, the glucagon/cAMP pathway had no influence on hypoxia-inducible factor-1 (HIF-1) mRNA and protein levels. Thus, CREB binding to the HIF-1 responsive elements in PAI-1 promoter mediates the glucagon effect in the liver.