Curcumin/TGF-ß1 siRNA loaded solid lipid nanoparticles alleviate cerebral injury after intracerebral hemorrhage by transnasal brain targeting.

Intracerebral hemorrhage (ICH) is a prevalent cerebrovascular disorder. The inflammation induced by cerebral hemorrhage plays a crucial role in the secondary injury of ICH and often accompanied by a poor prognosis, leading to disease exacerbation. However, blood-brain barrier (BBB) limiting the penetration of therapeutic drugs to the brain. In this paper, our primary objective is to develop an innovative, non-invasive, safe, and targeted formulation. This novel approach aims to synergistically harness the combined therapeutic effects of drugs to intervene in inflammation via a non-injectable route, thereby significantly mitigating the secondary damage precipitated by inflammation following ICH. Thus, a novel "anti-inflammatory" cationic solid lipid nanoparticles (SLN) with targeting ability were constructed, which can enhance the stability of curcumin(CUR) and siRNA. We successfully developed SLN loaded with TGF-ß1 siRNA and CUR (siRNA/CUR@SLN) that adhere to the requirements of drug delivery system by transnasal brain targeting. Through the characterization of nanoparticle properties, cytotoxicity assessment, in vitro pharmacological evaluation, and brain-targeting evaluation after nasal administration, siRNA/CUR@SLN exhibited a nearly spherical structure with a particle size of 125.0±1.93 nm, low cytotoxicity, high drug loading capacity, good sustained release function and good stability. In vitro anti-inflammatory results showcasing its remarkable anti-inflammatory activity. Moreover, in vivo pharmacological studies revealed that siRNA/CUR@SLN can be successfully delivered to brain tissue. Furthermore, it also elicited an effective anti-inflammatory response, alleviating brain inflammation. These results indicated that favorable brain-targeting ability and anti-inflammatory effects of siRNA/CUR@SLN in ICH model mice. In conclusion, our designed siRNA/CUR@SLN showed good brain targeting and anti-inflammatory effect ability after nasal administration, which lays the foundation for the treatment of inflammation caused by ICH and offers a novel approach for brain-targeted drug delivery and brings new hope.

MRI measurements the linear volume of posterior cranial fossa in patients with hemifacial spasm.

To explore the pathogenesis of hemifacial spasm (HFS) and the effect of posterior fossa volume on postoperative complications. The measurements of the antero-posterior diameter of foramen magnum, the length of supraocciput, the angle of tentorium cerebelli, clivus and occipital bone were performed on MRI. The data of measurements and postoperative complications were then analyzed and statistically examined. The antero-posterior diameter of the foramen magnum was smaller in HFS group (34.98 ± 2.83) mm than in control group (35.83 ± 2.67) mm (P < 0.05); The length of supraocciput was smaller in HFS group (44.67 ± 4.48) mm than in control group (45.84 ± 4.25) mm (P < 0.05); The angle of tentorium cerebelli was larger in HFS group (41.03 ± 5.01)°than in control group (37.28 ± 4.31)° (P < 0.05); The angle of clivus was smaller in HFS group (52.71 ± 6.22)° than in control group (56.39 ± 6.61)° (P < 0.05). The operation time was significantly longer in crowding group (107.90 ± 26.20) min than in non-crowding group (96.48 ± 20.52) min (P < 0.05); The incidence of postoperative facial paralysis was significantly higher in crowding group (16.19%) than in non-crowding group (7.20%) (P < 0.05); The incidence of postoperative hearing loss was significantly higher in crowding group (13.33%) than in non-crowding group (4.00%) (P < 0.05). Factors such as shorter antero-posterior diameter of foramen magnum, lower tentorium cerebelli, and shorter length of supraocciput in patients with HFS indicate the posterior fossa dysplasia and promote the occurrence of HFS. The crowding of the posterior fossa will increase the difficulty of the surgery and the incidence of postoperative facial paralysis and hearing loss.

Association Study of Apolipoprotein E Gene Polymorphism With Incidence and Delayed Resolution of Hemifacial Spasm.

Objective: This study investigates the correlation between Apolipoprotein E gene (APOE) polymorphism and the incidence and delayed resolution of hemifacial spasms. Methods: The APOE genotypes of 151 patients with hemifacial spasm and 73 control cases were determined by cleaved amplification polymorphism sequence-tagged sites. The distribution of three APOE alleles (ε2, ε3, and ε4) in two groups and the delayed resolution rate in 6 genotypes were calculated and statistically analyzed. Results: The proportion of patients with APOE ε3/ε4 genotype in the hemifacial spasm group (25.17%) was significantly higher than that in the control group (12.33%) (P = 0.027). In terms of allele frequency, the proportion of the APOE ε4 allele in the hemifacial spasm group (15.56%) was significantly higher than that in the control group (6.85%) (P = 0.009). Meanwhile, the proportion of APOE ε4 allele carriers in the hemifacial spasm group (29.80%) was significantly higher than that in the control group (13.7%) (P = 0.009). Logistic regression analysis showed that the ε4 allele significantly increased the incidence of hemifacial spasm (OR 2.675, 95%CI 1.260-5.678, P = 0.010). Among the 32 patients with a delayed resolution, the ε3/ε3 and ε3/ε4 had the highest proportion in 6 genotypes. The delayed resolution rate of APOE ε3/ε4 (34.21%) was significantly higher than APOE ε3/ε3 (17.78%) (P < 0.05). The delayed resolution rate of APOE ε4 carriers was the highest (33.33%) in the 3 allele carriers, but there was no significant difference among the 3 allele carriers (P = 0.065). Conclusion: The polymorphism of APOE is relevant to the incidence rate of hemifacial spasms. APOE ε4 allele increases the incidence of hemifacial spasm. The APOE ε4 allele may promote the occurrence of delayed resolution.