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Background: Idiopathic normal pressure hydrocephalus (iNPH) is the only reversible cause of dementia, but many patients fail to receive shunt surgery in time due to underdiagnosis. This study aimed to determine the relationship between surgery timepoint and sustained postoperative improvement in patients with iNPH. Methods: We divided the patients into the early surgery group (0–3 months) and the late surgery group (> 3 months) according to the duration from the disease onset to surgery. Patients from 3 general hospitals in different provinces of China were included. Primary endpoints included improvements on the idiopathic normal pressure hydrocephalus grading scale (INPHGS) and modified Rankin Scale (mRS). Results: A total of 120 patients were included in the study. The mean age was 62.76 ± 12.27, the mean duration of symptoms was 22.00 ± 37.99 months, the mean INPHGS was 7.15 ± 1.759 (cognitive: 2.71 ± 0.91; gait: 2.47 ± 0.95; urinary: 1.96 ± 0.88), and the mean mRS were 2.45 ± 0.77. In the early surgery group, patients’ symptoms improved continuously from discharge to 1-year follow-up. Regarding mRS improvement, the early surgery group is superior to the late surgery group at postoperative time points and 1-year follow-up (p < 0.05). Conclusions: The results of this multicenter study indicate that early shunting promotes sustained improvement in patients with iNPH.

PurposeWe tried to explore the potential role of the α-Lipoic acid-plus (LAP) in endothelial injury in vitro and vivo models. Simultaneously, possible endovascular protective mechanisms of LAP were also investigated further. MethodsIn vitro, oxyhemoglobin (OxyHb) stimulating human umbilical vein endothelial cells (HUVECs) simulated intimal injury. In vivo, carotid artery angioplasty injury was used to generate a model of rat carotid artery intimal injury (CAII). HUVECs and rats were treated with desferrioxamine (DFO) and LAP. ResultsIn experiment 1, we found that the expressions of Cathepsin B/D in endothelial tissue increased and reached peak point in 48 hours post rat CAII. In experiment 2, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin, Transferrin Receptor (TfR) markedly increased after CAII and reversed by DFO and LAP treatments. Besides, DFO and LAP treatments also reduced oxidative stress level and endothelial cells (ECs) necrosis of the damaged endometrium. In experiment 3, firstly, the protein levels of Cathepsin B/D, cleaved-caspase-3, Bax, Ferritin and TfR apparently increased post OxyHb stimulation, which were further aggravated by the addition of iron and decreased by DFO and LAP treatments. Moreover, DFO and LAP significantly ameliorated oxidative stress level, HUVECs injury, iron level, mitochondrial damage and were beneficial to maintain lysosomal integrity. Finally, LAP may have exerted more significant endovascular protective effects than DFO.Conclusions LAP probably exerted endovascular protective effects via inhibiting the apoptosis pathway mediated by intralysosomal Cathepsins by chelating excessive iron in endothelial lysosomes post intimal injury.