A comparison of the efficacy of computed tomography-guided minimally invasive puncture and drainage and craniotomy for hematoma evacuation in the treatment of cerebellar hemorrhage.

OBJECTIVE: This study aimed to compare the efficacy of computed tomography (CT)-guided minimally invasive puncture and drainage (MIPD) and craniotomy for hematoma evacuation in the treatment of cerebellar hemorrhage. METHODS: This single-center prospective cohort study was conducted from January 2020 to February 2023. During the study period, 40 patients with cerebellar hemorrhage who underwent CT-guided MIPD treatment were enrolled in the CT-guided MIPD (CTGMIPD) group, and 40 patients with the cerebellar hemorrhage who had a propensity score matching that of the CTGMIPD group and who underwent craniotomy for hematoma evacuation were enrolled in the standard craniotomy (SC) group. The primary outcome indicators were the 6-month mortality of the patients and the proportion of survivors with a modified Rankin Scale (mRS) scores of 1 or 2. The secondary outcome indicators were the cerebellar hematoma volume, National Institutes of Health Stroke Scale (NIHSS) score, Glasgow Coma Scale (GCS) score, incidence of postoperative complications, length of hospital stay, and medical costs. In addition, data concerning the patients who died during the study period were further analyzed. RESULTS: At the 6-month follow-up, there was no significant difference in mortality between the two groups, although the proportion of patients with an mRS scores of 1 or 2 was significantly higher in the CTGMIPD group when compared with the SC group (P = 0.015). No significant differences were observed in the hematoma volume, NIHSS score, and GCS score between the two groups. By contrast, the incidence of postoperative complications, length of hospital stay, and medical costs were significantly lower in the CTGMIPD group than in the SC group (all P < 0.05). When compared with the SC group, the proportion of dead patients with a hematoma volume greater than 30 ml was higher in the CTGMIPD group (P = 0.03). Moreover, after stratification of the patients with a preoperative GCS score ≤8, the CTGMIPD group had a significantly higher mortality rate than the SC group (P = 0.04). CONCLUSION: The efficacy of CT-guided MIPD in the treatment of cerebellar hemorrhage is close to that of craniotomy for hematoma excavation, although the complication and disability rates of the former are significantly lower than those of the latter. When the preoperative hematoma volume is less than 30 mL or the preoperative GCS score is greater than 8, CT-guided MIPD represents a better choice for the treatment of cerebellar hemorrhage than craniotomy for hematoma evacuation.

Aspirin inhibits the proliferation and migration of gastric cancer cells in p53-knockout mice.

The aim of the present study was to investigate the effect of aspirin on the cell proliferation and migration of gastric cancer cells in p53-knockout mice. Twenty p53-/- male mice aged 6 to 7 weeks, with an average weight of 20±3 g were used. The model of gastric cancer was established by the implantation of a mouse forestomach carcinoma cell line, subcutaneously, at the back of the neck, and then the mice were randomly divided into two groups after establishment of the model (control group, n=10; experimental group, n=10). Aspirin (250 mg/kg) was added to the food in the experimental group one day before model establishment, until the end of the experiment. Mice in the control group were given regular food without aspirin. All mice were sacrificed 3 months afterwards, and gastric cancer tissues were harvested. MTT assay was used to detect the proliferation of the tumor cells. Tumor cell number was also observed. Migration ability was detected by scratch assay, and E-cadherin protein expression was evaluated by immunofluorescence. The results revealed that the proliferation ability of tumor cells in the experimental group was lower than that in the control group. In addition, cell numbers were significantly decreased and the migration ability was diminished. The expression of E-cadherin was also increased in the experimental group, and the differences were statistically significant (P<0.05). In conclusion, aspirin inhibited the cell proliferation and migration of gastric cancer cells in mice.

Anti-amnesic effect of neurosteroid PREGS in Aß25-35-injected mice through σ1 receptor- and α7nAChR-mediated neuroprotection.

A single intracerebroventricular injection of ß-amyloid 25-35 peptide (Aß(25-35)) (9 nmol/mouse) induces the spatial cognitive deterioration and approximately 50% loss of pyramidal cells in hippocampal CA1 region within 1 week. The present study focused on exploring the effects of neurosteroid pregnenolone sulfate (PREGS), in comparison with the selective agonists of sigma-1 receptor (σ(1)R) and α7 nicotinic acetylcholine receptor (α7nAChR), on the cognitive deficits and the death of pyramidal cells in Aß(25-35)-mice. Herein, we reported that the administration of PREGS (1-100 mg/kg) for 7 days after Aß(25-35)-injection could dose-dependently ameliorate the cognitive deficits and attenuate the apoptosis of pyramidal cells. Either the σ(1)R antagonist NE100 or the α7nAChR antagonist MLA could block the neuroprotection of PREGS in Aß(25-35)-mice. Both the σ(1)R agonist PRE084 and the α7nAChR agonist DMXB could mimic the PREGS-neuroprotection against the Aß(25-35)-neurotoxicity. The neuroprotection of PRE084 was attenuated by MLA, but the DMXB-action was insensitive to NE100. The neuroprotection of PREGS, PRE084 or DMXB was blocked by the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002, whereas only the effect of PREGS or PRE084 was sensitive to the MAPK/ERK kinase (MEK) inhibitor U0126. PREGS prevented Aß(25-35)-inhibited Akt (Serine/threonine kinase) phosphorylation leading to increase in caspase-3 activity, which was σ(1)R- and α7nAChR-dependent. By contrast, PREGS-rescued reduction of extracellular signal-related kinase-2 (ERK2) phosphorylation in Aß(25-35)-mice only required the activation of σ(1)R. Blockage of PREGS-neuroprotection by LY294002 significantly attenuated its anti-amnesic effect in Aß(25-35)-mice. The findings indicate that the anti-amnesic effects of PREGS in Aß(25-35)-mice depend on the σ(1)R- and α7nAChR-mediated neuroprotection.

Neurosteroid PREGS protects neurite growth and survival of newborn neurons in the hippocampal dentate gyrus of APPswe/PS1dE9 mice.

Neurosteroids pregnenolone-sulfate (PREGS) and dehydroepiandrosterone (DHEA) have been shown to enhance neurogenesis in the hippocampal dentate gyrus (DG) of adult rodents. In Alzheimer's disease (AD) brain, the levels of these neurosteroids are known to be altered compared to age-matched non-demented controls. The aim of this study was to examine the effects of PREGS and DHEA on the hippocampal neurogenesis in 8-month-old male APPswe/PS1dE9 transgenic (APP/PS1) mice that show amyloid plaques and impaired spatial cognitive performance. In the DG of APP/PS1 mice the proliferation of progenitor cells was increased, while the neurite growth and survival of newborn neuronal cells were markedly impaired. Treatment with PREGS or DHEA rescued perfectly the hypoplastic neurite of newborn neurons in APP/PS1 mice, while neither of them affected the over-proliferation of progenitor cells. Notably, the administration of PREGS, but not DHEA, to APP/PS1 mice could protect the survival and maturation of newborn neuronal cells, which was accompanied by the improvement of spatial cognitive performance. The results indicate that treatment of AD like brains of APP/PS1 mice with PREGS might protect the hippocampal neurogenesis, leading to the improved spatial cognitive performance.

DHEA prevents Aß25-35-impaired survival of newborn neurons in the dentate gyrus through a modulation of PI3K-Akt-mTOR signaling.

Infusion (i.c.v.) of beta-amyloid 25-35 (Abeta(25-35)) stimulates proliferation of progenitor cells in the hippocampal dentate gyrus (DG) of adult male mice, but a large population of the newborn cells will die in the 2nd week after birth, a critical period for neurite growth. Neurosteroid dehydroepiandrosterone (DHEA) has been demonstrated to promote neurite growth. Herein, we report that the DHEA-treatment on 6-12 days after BrdU-injection (BrdU-D(6-12)) dose-dependently attenuates the loss of newborn neurons induced by Abeta(25-35)-infusion. The DHEA-neuroprotection was blocked by the sigma(1) receptor antagonist NE100 and mimicked by the sigma(1) receptor agonist PRE084 when administered on BrdU-D(6-12). The DHEA-action was sensitive to the PI3K inhibitor LY294002 and the mammalian target of rapamycin (mTOR) inhibitor rapamycin. The Abeta(25-35)-infusion decreased the levels of Akt, mTOR and p70S6k phosphorylation, which could be rescued by DHEA-treatment in a sigma(1) receptor-dependent manner. Furthermore, the Abeta(25-35)-infusion led to a decrease in the dendritic density and length of doublecortin positive cells in the DG, which also was improved by the DHEA-treatment on BrdU-D(6-12). These findings suggest that DHEA prevents the Abeta(25-35)-impaired survival and dendritic growth of newborn neurons through a sigma(1) receptor-mediated modulation of PI3K-Akt-mTOR-p70S6k signaling.