Ryo Yoshimura

Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of progressive Parkinson’s disease

Trophic effects of neurturin, a member of the glial cell line-derived neurotrophic factor-family, have been demonstrated on mesencephalic dopaminergic neurons, suggesting its therapeutic potential for Parkinsons disease. This study was designed to test the neuroprotective and regenerative effects of an intrastriatal injection of neurturin based on behavioral, neurochemical and histochemical changes in a rat model of progressive Parkinsons disease. An extensive and progressive dopaminergic lesion was unilaterally made by intrastriatal convection-enhanced delivery of 6-hydroxydopamine (6-OHDA), in which 20 microg of 6-OHDA dissolved in 20 microl of vehicle was infused at a rate of 0.2 microl/min. For neuroprotection study, recombinant human neurturin (5 microg in 5 microl of vehicle) was stereotaxically injected into the unilateral striatum. The 6-OHDA lesion was made on the ipsilateral side 3 days after the neurturin treatment. Tyrosine hydroxylase (TH)-immunoreactive neurons of the substantia nigra were protected from progressive degeneration in the neurturin-treated animals compared with the vehicle-treated animals 2 and 8 weeks after the 6-OHDA lesion. Eight weeks after the 6-OHDA lesion, dopamine concentration significantly increased in the striatum of neurturin-treated animals with improvement of methamphetamine-induced rotation behavior. For neuroregeneration study, 5 microg of neurturin was injected into the striatum 12 weeks after the 6-OHDA lesion. Four weeks after neurturin or vehicle injection, there were no significant differences in the survival of nigral TH-immunoreactive neurons between the groups. However, TH-immunoreactive fibers were thicker and more abundant in the striatum of the neurturin-treated rats compared to those of the control group, suggesting neurturin-induced growth of the dopaminergic axons. Striatal dopamine levels also significantly increased in the neurturin-treated rats compared with those in the control group of rats, accompanied by the recovery of methamphetamine-induced rotation in the neurturin-treated rats. In conclusion, an intrastriatal injection of neurturin is a useful method to protect nigral dopaminergic neurons from extensive cell death in a model of progressive Parkinsons disease, as well as to promote the axonal regeneration and dopaminergic function.

Endovascular recanalization of the completely occluded internal carotid artery using a flow reversal system at the subacute to chronic stage.

OBJECT The efficacy and pitfalls of endovascular recanalization were evaluated in cases of internal carotid artery (ICA) occlusion in the subacute to chronic stage. METHODS Fourteen cases (15 lesions) of symptomatic ICA occlusion with hemodynamic compromise or recurrent symptoms were treated at the subacute to chronic stage using an endovascular technique. The Parodi embolic protection system was used during the recanalization procedure to prevent embolic stroke by reversing the flow from the distal ICA to the common carotid artery. RESULTS Recanalization of the occluded ICA was possible in 14 of 15 lesions. The occlusion points were 10 cervical ICAs and 4 petrous/cavernous ICAs in successfully recanalized cases. Ischemic symptoms disappeared completely after the treatment, and new ischemic symptoms did not appear related to the treated lesion. Single photon emission computed tomography findings demonstrated the improvement of hemodynamic compromise in all cases. One case showed right middle cerebral artery branch occlusion during the procedure, but this patients neurological symptoms were stable due to preexisting hemiparesis. Endovascular recanalization was possible and effective in improving hemodynamic compromise. However, there are still several problems with this technique, such as hyperperfusion syndrome after recanalization, cerebral embolism during treatment, durability after treatment, and identification of the occlusion point before treatment. CONCLUSIONS Endovascular recanalization using an embolic protection device can be considered as an alternative treatment for symptomatic ICA occlusion with hemodynamic compromise or refractoriness to antiplatelet therapy, even in the subacute to chronic stage of the illness.

Reappraisal of primary balloon angioplasty without stenting for patients with symptomatic middle cerebral artery stenosis.

There is a controversy regarding the safety and efficacy of intracranial stenting. We describe our experience with primary balloon angioplasty without stenting for symptomatic middle cerebral artery (MCA) stenosis. All patients who underwent balloon angioplasty without stenting for MCA stenosis between 1996 and 2010 were retrospectively reviewed. We evaluated technical success rates, degrees of stenosis, and stroke or death within 30 days. Among patients who were followed-up for > 1 year we evaluated latest functional outcomes, stroke recurrence at 1 year, and restenosis. In total 45/47 patients (95.7%) were successfully treated. Average pre- and postprocedure stenosis rates were 79.9% and 39.5%, respectively. Three neurological complications occurred within 30 days: one thromboembolism during the procedure; one lacunar infarction; and one fatal intraparenchymal hemorrhage after the procedure. Stroke or death rate within 30 days was 6.4%. Thirty-three patients were available for follow-up analysis with a mean period of 51.5 months. The combined rate of stroke or death within 30 days and ipsilateral ischemic stroke of the followed-up patients within 1 year beyond 30 days was 9.4%. Restenosis was observed in 26.9% of patients and all remained asymptomatic. In our retrospective series, balloon angioplasty without stenting was a safe, effective modality for symptomatic MCA stenosis. For patients refractory to medical therapy, primary balloon angioplasty may offer a better supplemental treatment option.

Emergent carotid artery stenting using a flow reversal system for acute atherosclerotic occlusion of the internal carotid artery.

The natural history of acute occlusion of the cervical internal carotid artery (ICA) is unfavorable [1]. Treatment includes intravenous or intra-arterial administration of tissue plasminogen activator (tPA), using retrieval devices, percutaneous transluminal balloon angioplasty, carotid artery stenting (CAS), and carotid endarterectomy [2, 3, 12, 13, 16]. Only a few reports have shown the efficacy of emergent CAS for acute occlusion of the ICA [4, 5, 9]. In those reports, the guidewire was crossed through the occluded lesion with no embolic protection. We report the efficacy of emergent CAS with a flow reversal system for acute atherosclerotic occlusion of the cervical ICA. We treated three cases within 24 h from stroke onset (Table 1). In all of the cases, recanalization was achieved with no embolic stroke during the procedure. No technical or periprocedural complications occurred. All patients showed improvement of symptoms after emergent CAS.