Endovascular recanalization for symptomatic subacute and chronically occluded internal carotid artery: feasibility, safety, a modified radiographic classification system, and clinical outcomes.

PURPOSE: To evaluate the feasibility and safety of endovascular recanalization for symptomatic subacute and chronic internal carotid artery occlusion (ICAO); to propose a newly modified radiographic classification of ICAO that can rigorously identify suitable candidates for endovascular ICAO treatment. METHODS: We included 42 consecutive patients who had ICAO with ischaemic symptoms refractory to medical therapy. We examined the symptomatology, complications, follow-up results and radiographic images of ICAO receiving attempted endovascular treatment. We attempted to stratify all radiographic images into categories based on morphological occlusion patterns, occlusion segments and distal ICA reconstitution on digital subtraction angiography (DSA). RESULTS: Four types (A-D) of radiographic ICAO were identified. We redefined type B as having a tapered stump but no distal lumen. The rate of successful recanalization was 83.33% (35/42 ICAOs; type A, 18/20; type B, 7/10; type C, 10/11; type D, 0/1). The perioperative complication rate was 11.90% (5/42), including 3 asymptomatic distal embolisms, 1 symptomatic cerebral infarction and 1 asymptomatic carotid artery dissection. None of these technique-related complications led to severe neurological damage or death. Modified Rankin Scale (mRS) scores after 1-20 months of follow-up were significantly decreased in successfully revascularized patients (P < 0.001). There was no significant change in mRS scores in the 7 patients in whom recanalization failed (P > 0.05). CONCLUSIONS: Endovascular recanalization seems to achieve technical success and clinical improvement for symptomatic subacute and chronic ICAO. Additionally, our newly modified radiographic classification of ICAO may be valuable in assessing the technical feasibility and safety of procedures in symptomatic ICAO patients.

Triptolide derivatives as potential multifunctional anti-Alzheimer agents: Synthesis and structure-activity relationship studies.

Owning to the promising neuroprotective profile and the ability to cross the blood-brain barrier, triptolide has attracted extensive attention. Although its limited solubility and toxicity have greatly hindered clinical translation, triptolide has nonetheless emerged as a promising candidate for structure-activity relationship studies for Alzheimer's disease. In the present study, a series of triptolide analogs were designed and synthesized, and their neuroprotective and anti-neuroinflammatory effects were then tested using a cell culture model. Among the triptolide derivatives tested, a memantine conjugate, compound 8, showed a remarkable neuroprotective effect against Aß1-42 toxicity in primary cortical neuron cultures as well as an inhibitory effect against LPS-induced TNF-α production in BV2 cells at a subnanomolar concentration. Our findings provide insight into the different pharmacophores that are responsible for the multifunctional effects of triptolide in the central nervous system. Our study should help in the development of triptolide-based multifunctional anti-Alzheimer drugs.