Lifei Lian

Baicalein inhibits α-synuclein oligomer formation and prevents progression of α-synuclein accumulation in a rotenone mouse model of Parkinson's disease

Parkinsons disease (PD) is a progressive neurodegenerative disease. α-Synuclein (α-syn) oligomers play a critical role in the progression of PD. Baicalein, a typical flavonoid compound, can inhibit the formation of the α-syn oligomers, and disaggregate existing α-syn oligomers in vitro. However, whether baicalein could inhibit or disaggregate α-syn oligomers in vivo has not been investigated. Therefore, this study was designed to investigate the inhibitory effects of baicalein on α-syn oligomers in vivo and to explore the possible mechanisms of such inhibition. A chronic PD mouse model was created by continuous intragastric administration of rotenone (5mg/kg, 12weeks). Baicalein (100mg/kg) was intraperitoneally injected from 7week to 12week. Our result showed that the amount of α-syn, changes in the levels of the striatal neurotransmitters, and the behavioral changes found in the chronic PD mouse model were prevented after the baicalein injections. Although baicalein did not decrease α-syn mRNA expression, α-syn oligomers were significantly decreased in the ileum, thoracic spinal cord, and midbrain. Furthermore, transmission electron microscopy analysis showed that baicalein could prevent α-syn monomers from the oligomer formation in vitro. Taken together, these results suggest that baicalein could prevent the progression of α-syn accumulation in PD mouse model partly by inhibiting formation of the α-syn oligomers.

Intraclot recombinant tissue-type plasminogen activator reduces perihematomal edema and mortality in patients with spontaneous intracerebral hemorrhage

The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10–16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39–0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.SummaryThe study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10–16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39–0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.

Pneumocephalus following the minimally invasive hematoma aspiration and thrombolysis for ICH.

Abstract Introduction. The objective of this study was to clarify whether pneumocephalus occurred and affected the outcome following minimally invasive hematoma aspiration and thrombolysis for intracerebral hemorrhage (ICH). Materials and methods. A prospective case note review on all ICH patients treated with the micro-invasive procedure presenting to our division from 2006 to 2011 was conducted. Demographic, clinical, and outcome data were documented; head CT scans were applied postoperatively to identify the intracranial air collection. The ICH victims with pneumocephalus were included into Group A and the others into Group B. A multi-variant analysis was performed between Groups A and B to examine the effect of pneumocephalus on the prognosis. Results. Data were collected on a total of 134 cases in this study, among whom 72.38% developed pneumocephalus postoperatively. No significant difference was demonstrated in terms of the preoperative and postoperative hematoma volume, Glasgow Coma Scale (GCS) score, middle line shift (MLS), and 30-day mortality rate between Groups A and B, respectively. Moreover, the long-term outcome rated by GCS of these two groups was also similar. Logistic regression analysis indicated double-needle puncture be an independent risk factor for both postoperative pneumocephalus (OR, 2.478; 95% CI, 1.010–6.080; P = 0.045) and its degree (OR, 11.84; 95%CI, 4.141–30.208; P < 0.001). Conclusion: The present study shows that pneumocephalus is common following the minimally invasive hematoma aspiration and thrombolysis for ICH but may not affect the outcome. And double-needle puncture may be the risk factor for pneumocephalus.

Intranasal nerve growth factor attenuating the seizure onset via p75R/Caspase pathway in the experimental epilepsy

BACKGROUND Nerve growth factor (NGF) shows neuroprotection while it is hard to cross the blood-brain barrier due to its large molecular weight. Our study used intranasal delivery of NGF to treat the experimental epilepsy. METHODS The seizure was induced by injection of pentylenetetrazol (40mg/kg) into the rat. Based on the behavior performance, the successful models were randomized into control and NGF groups, given medium or NGF intranasally, respectively. The onset and duration of seizure were recorded. The neuron loss was assessed by immunohistochemistry and TUNEL staining. The expressions of Caspase-3, p75R and TrkA were measured by western blotting. RESULTS Intranasal NGF significantly reduced the seizure onset and shortened the seizure duration. Intranasal NGF alleviated the neuron loss in the epileptic brain. The number of TUNEL-positive cells in the NGF group was less than that in the control group (P<0.05). Overexpression of Caspase-3 and activation of p75R induced by seizure were inhibited by intranasal NGF. CONCLUSION Intranasal NGF protected neurons in the epileptic brain by inactivation of p75R/Caspase pathway. Intranasal NGF may be a novel therapeutic strategy for epilepsy.

Effects of endovascular therapy on acute ischemic stroke:An updated meta-analysis of randomized controlled trials.

OBJECTS To clarify the effects of endovascular therapy (ET) for acute ischemic stroke (AIS) patients, we conducted an updated meta-analysis using data from randomized controlled trials (RCTs). METHODS We searched major electronic databases for RCTs comparing ET with intravenous thrombolysis (IVT) or other standard treatments for AIS patients. Eligible and high-quality RCTs were included in the meta-analysis. The overall estimates were demonstrated as an odds ratio (OR) with 95% confidence interval (CI) and P value. RESULTS Thirteen high-quality trials met the inclusion criteria and were analyzed. Patients treated by ET were more likely to have good functional outcomes (OR, 1.70; 95% CI, 1.32-2.19; P< 0.0001) and lower mortality rates (OR, 0.77; 95% CI, 0.60-0.98; P = 0.03) at 90 days than patients treated by IVT or standard treatment. There was no significant difference in the rate of symptomatic intracerebral hemorrhage [sICH] (OR, 1.18; 95% CI, 0.73-1.91; P = 0.50). CONCLUSIONS ET is superior to both IVT and standard treatment in providing functional improvement and reducing the mortality rate at 90 days, while not increasing the risk of sICH for the treatment of AIS.

Extensive basal ganglia hematomas treated by local thrombolysis versus conservative management – a comparative retrospective analysis

Abstract Objectives: Single-target puncture plus catheter insertion into the clot is a routine step in hematoma aspiration and local thrombolysis for spontaneous intracerebral haemorrhage (ICH). However, multiple-target puncture of this procedure may imply faster hematoma reduction for large-area ICH. We retrospectively examined the outcomes after clot aspiration plus local thrombolysis with single-/double-target and conservative therapy for extensive basal ganglic hematomas. Methods: A case note review was conducted on a consecutive series of ICH patients in a single centre with huge basal ganglia hematomas who underwent clots aspiration and thrombolysis or pure medical therapy. We analysed the clinical presentation, radiological features and treatment outcomes of ICH patients in single-target group, double-target group and conservative group. Results: A total of 92 ICH cases were included in this study. At the post-treatment assessment, the average level by hematoma size in single-target and double-group was respectively smaller than that in the conservative group (20.61 ml vs. 15.75 ml vs 60.53 ml, p < 0.01). The 30-day case fatality rate in conservative group was respectively significantly higher than that in single-target and double-target groups (50% vs. 14.70% vs. 20.59%, p < 0.01). At the time of 6-month follow-up, the proportion of good survival in conservative group was respectively remarkably less than that in single- and double-target group (29.17% vs.64.71% vs. 67.65%, p < 0.01). But no difference was detected with respect to 30-day mortality or long-time outcome between the two micro-invasive groups (p = 0.53 and 0.798, respectively). Conclusion: Our data suggested for the massive basal ganglia hematomas, clot aspiration and thrombolysis can improve the short- and long-term prognosis compared with the pure conservative therapy. But, no evidence was found to demonstrate double-target of this procedure to be more effective than single-target to improve the outcome.