The learning curve associated with intracranial angioplasty and stenting: analysis from a single center.

BACKGROUND: Intracranial angioplasty and stenting is an optional treatment for patients with symptomatic intracranial artery stenosis (IAS) who have failed to respond to standard medical therapy. We aimed to analyze the effect of the operator's learning curve in our center in terms of the safety of intracranial angioplasty and stenting. METHODS: In this retrospective study, we analyzed patients treated with intracranial angioplasty and stenting in our center between January 2007 and December 2015. The endpoint was peri-procedure complications within 30 days. A risk-adjusted cumulative sum chart was used for the learning curve analysis. Multivariable logistic analysis was also used to evaluate the effect of the learning curve on intracranial angioplasty and stenting. RESULTS: A total of 329 patients were included. The overall peri-procedure complication rate was 8.21% (27/329). Multivariate logistic regression analysis showed that operators with experience of >20 cases [odds ratio (OR) =0.229; 95% confidence interval (CI): 0.059-0.893] and >40 cases (OR =0.024; 95% CI: 0.006-0.093) were associated with a low risk of complications compared with operators with experience of ≤20 cases. Furthermore, patients with hypertension (OR =3.595; 95% CI: 1.104-11.702) and stenosis of Mori classification C (OR =28.562; 95% CI: 4.788-170.395) were associated with a high risk of complications. The observed outcome was better than expected (more negative deflections) after the 30th consecutive case. CONCLUSIONS: The level of operator experience can influence the risk of peri-procedure complications associated with intracranial angioplasty and stenting. A total of 30 consecutive cases is required for an operator to overcome the learning curve.

Changes in mitochondrial ultrastructure in SH-SY5Y cells during apoptosis induced by hemin.

Hemorrhagic stroke is associated with high morbidity and mortality. Hemin is a decomposition product of hemoglobin that is related to neuronal apoptosis after hemorrhage, although the molecular basis for this association remains unclear. To address this issue, the present study investigated hemin-induced changes in the apoptotic index and mitochondrial ultrastructure in SH-SY5Y cells. Cell viability was evaluated using Cell Counting Kit-8 and by terminal transferase dUTP nick-end labeling, western blotting, and flow cytometry. Changes in mitochondrial ultrastructure were examined by super-resolution three-dimensional structured illumination microscopy. We found that cleaved-caspase-3 expression and the number of apoptotic cells increased in a time-dependent manner upon hemin treatment, which was associated with mitochondrial fragmentation. Our data suggest that hemin induces apoptosis and mitochondrial fission in neuronal cells. Thus, therapeutic strategies that target hemin could mitigate the damage caused by hemorrhagic stroke.

Mdivi-1 Alleviates Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats, Possibly via Inhibition of Drp1-Activated Mitochondrial Fission and Oxidative Stress.

Mdivi-1 is a selective inhibitor of mitochondrial fission protein, Drp1, and can penetrate the blood-brain barrier. Previous studies have shown that Mdivi-1 improves neurological outcomes after ischemia, seizures and trauma but it remains unclear whether Mdivi-1 can attenuate early brain injury after subarachnoid hemorrhage (SAH). We thus investigated the therapeutic effect of Mdivi-1 on early brain injury following SAH. Rats were randomly divided into four groups: sham; SAH; SAH + vehicle; and SAH + Mdivi-1. The SAH model was induced by standard intravascular perforation and all of the rats were subsequently sacrificed 24 h after SAH. Mdivi-1 (1.2 mg/kg) was administered to rats 30 min after SAH. We found that Mdivi-1 markedly improved neurologic deficits, alleviated brain edema and BBB permeability, and attenuated apoptotic cell death. Mdivi-1 also significantly reduced the expression of cleaved caspase-3, Drp1 and p-Drp1(Ser616), attenuated the release of Cytochrome C from mitochondria, inhibited excessive mitochondrial fission, and restored the ultra-structure of mitochondria. Furthermore, Mdivi-1 reduced levels of MDA, 3-NT, and 8-OHdG, and improved SOD activity. Taken together, our data suggest that Mdivi-1 exerts neuroprotective effects against cell death induced by SAH and the underlying mechanism may be inhibition of Drp1-activated mitochondrial fission and oxidative stress.