MicroRNA-126-3P targets PIK3R2 to ameliorate autophagy and apoptosis of cortex in hypoxia-reoxygenation treated neonatal rats.

Here, we explored a possible mechanism of microRNA-126-3p (miR-126-3p) on neonatal rats with hypoxia-reoxygenation injury (HI). After administering HI to newborn Sprague-Dawley rats, the expression of miR-126-3p in the brain injury was assessed by RT-PCR. A miR-126-3p mimic and inhibitor were treated in the HI neonatal rats. The water maze test, TTC, HE, Nissl and TUNEL staining were separately implemented to test the effects of miR-126-3p on the HI-treated neonatal rats. At the same time, the phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) expression in the damaged cortex region was analyzed. In vitro, cortical neurons were cultured and treated with oxygen and glucose deprivation (OGD), then transfected miR-126-3p mimic, PIK3R2 overexpression lentivirus vector or silence of PIK3R2. The cell viability was observed by CCK-8. The autophagy of neurons was detected by acridine orange staining. In contrast to the sham-operated rats, the miR-126-3p expression significantly decreased, but PIK3R2 expression markedly rose in the cortex of HI rats. Injection of miR-126-3p mimic raised the learning and memory abilities through down-regulating the cerebral ischemic area, improving pathological damage of the cortex, reducing the neurons apoptosis of the cortex and down-regulating the autophagy-related and apoptosis-related proteins. Overexpression of PIK3R2, a miR-126-3p target, may reduce cell viability and boost autophagy and apoptosis. Silence of PIK3R2 promoted cell viability and inhibited cell apoptosis and autophagy. The consequences of miR-126-3p were comparable to those of PIK3R2 silencing. A new therapeutic target for HI injury in newborn rats is provided by the overexpression of miR-126-3p, which inhibits autophagy and death of cortical neurons by targeting PIK3R2 in HI-treated neonatal rats.

Short-term clinic observation of misalignment and rotational stability after implantable collamer lens implantation.

PURPOSE: We aimed to investigate misalignment (tilt and decentration) and rotational stability of the implantable collamer lens V4c 6 months after implantation and to explore the potential risk factors associated with postoperative misalignment and rotation. METHODS: A total of 36 eyes of 36 patients with high myopia and myopic astigmatism who underwent implantable collamer lens V4c implantation were included in this study. Tilt, decentration, and rotation of the implantable collamer lens were assessed postoperatively at l week, 1 month, 3 months, and 6 months. Correlation analysis was used to identify the potential risk factors for implantable collamer lens tilt, decentration, and rotation at 6 months postoperatively. Higher-order aberration was measured to evaluate the effect of implantable collamer lens misalignment on visual quality at pupil diameters of 4.0 mm and 6.0 mm. RESULTS: The tilt and decentration at the last follow-up were 2.43 ± 1.35° and 0.278 ± 0.160 mm, respectively. There was a significant positive correlation between tilt and decentration (r = 0.31, P = 0.046). No significant correlation was detected between implantable collamer lens decentration and internal higher-order aberrations (P > 0.05). The degree of implantable collamer lens rotation (3.11 ± 2.00°) was significantly associated with the vault (r = - 0.422, P = 0.01), while it was positively associated with the preoperative anterior chamber depth (r = 0.36, P = 0.034). No significant correlation was found between postoperative astigmatism and rotation (r = - 0.07, P = 0.351). CONCLUSIONS: The implantable collamer lens V4c provides relatively stable misalignment and rotation after implantation. The ICL lens vault is a potential risk factor for postoperative implantable collamer lens rotation. The absolute value of decentration and tilt was relatively small, which showed no correlation with internal higher-order aberration in short-term observation.

Comparison of the visual performance of iris-fixated phakic lens and implantable collamer lens to correct high myopia.

BACKGROUND: To compare visual performance between the iris-fixated phakic intraocular len (pIOL) and implantable collamer len (ICL) to correct high myopia. METHODS: Twenty-four eyes underwent iris-fixated pIOL implantation and 24 eyes underwent ICL implantation. At the 6-month follow-up, the best-corrected visual acuity (BCVA) and uncorrected distance visual acuity (UDVA) were compared between the iris-fixated pIOL and ICL groups. The objective scatter index (OSI), modulation transfer function (MTF) cutoff, and ocular aberrations were performed to evaluate postoperative visual quality between the two groups. RESULTS: No significant difference was found in UDVA, BCVA, and spherical equivalent between the iris-fixated pIOL and ICL groups (P > 0.05). Six months after surgery, the following values were significantly higher in the ICL group than in the iris-fixated pIOL group: MTF cutoff, strehl ratio and optical quality analysis system values at contrasts of 9 %, 20 %, and 100 % (P < 0.01). The OSI in the iris-fixated pIOL group was higher than in the ICL group 6 months after surgery (P < 0.01). All high-order aberrations were slightly more severe in the iris-fixated pIOL group than in the ICL group 6 months after surgery, although only trefoil (P = 0.023) differed significantly in this regard. CONCLUSIONS: Both iris-fixated lenses and ICLs can provide good visual acuity. ICLs confer better visual performance in MTF-associated parameters and induce less intraocular light scattering than iris-fixated pIOLs.

Neural Function Recovery and Safety of Mild Hypothermia Therapy Combined with Monosialotetrahexosylganglioside on Neonatal Asphyxia Complicated by Hypoxic Ischemic Encephalopathy.

OBJECTIVE: To explore the effect and safety of mild hypothermia therapy combined with monosialotetrahexosylganglioside (GM1) on neural function recovery of neonatal asphyxia complicated by hypoxic ischemic encephalopathy (HIE). METHODS: The clinical data of 90 neonates with HIE were retrospectively analyzed. According to the treatment methods, the neonates were divided into a routine group, a mild hypothermia group, and a combination group, with 30 cases in each group. The differences in neural function recovery, biochemical indexes, clinical signs recovery, efficacy, and complications were observed in the three groups after treatment. RESULTS: After treatment, the score of neonatal behavioral neurological assessment (NBNA) and level of superoxide dismutase (SOD) in the combination group were higher than those of the other two groups (P < 0.05). The levels of neuron-specific enolase (NSE), S-100ß protein, and plasma neuropeptide Y (NPY) in the combination group were lower than those in the other two groups, and the recovery time of consciousness, muscle tension, and reflex was shorter (P < 0.05). The combination group showed higher total effective rate and lower incidence of complications as compared with the other two groups (P < 0.05). CONCLUSION: Mild hypothermia therapy combined with GM1 for the treatment of neonatal asphyxia complicated by HIE can promote the recovery of neural function and reduce the incidence of complications in neonates.

Effect of mesenchymal stem cell transplantation on brain-derived neurotrophic factor expression in rats with Tourette syndrome.

The aim of the present study was to investigate the effect of bone marrow mesenchymal stem cell (MSC) transplantation on brain-derived neurotrophic factor (BDNF) expression in the striatum of Tourette syndrome (TS) rats. In addition, the possible mechanism of MSC transplantation in the treatment of TS was investigated. A total of 72 Wistar rats were randomly allocated into the control (sham surgery) group and the two experimental groups, including the TS+vehicle and TS+MSC. MSCs were co-cultured with 5-bromodeoxyuridine for 24 h for labeling prior to grafting. An autoimmune TS rat model was successfully established in the present study. Rat MSCs were cultured and expanded using density gradient centrifugation in vitro, identified by flow cytometry and then transplanted into the striata of the TS+MSC group rats. The mRNA and protein expression levels of BDNF were detected by RT-qPCR and ELISA, respectively. The results indicated that the stereotypic behavior of TS rats was reduced 7 days after MSC transplantation, while the mRNA and protein BDNF levels in the striatum increased, compared with the sham surgery group (P<0.05). In addition, the BDNF mRNA and protein expression level was lower in the striatum of TS+MSC transplantation, compared with that in TS+vehicle rats. In conclusion, intrastriatal transplantation of MSCs may provide relief from stereotypic TS behavior, since the BDNF level was reduced in TS rats after MSC transplantation.

Minocycline protects retinal ganglion cells after optic nerve crush injury in mice by delaying autophagy and upregulating nuclear factor-κB2.

BACKGROUND: Currently, no medicine is available that can prevent or treat neural damage associated with optic nerve injury. Minocycline is recently reported to have a neuroprotective function. The aims of this study were to exarmine the neuroprotective effect of minocycline on retinal ganglion cells (RGCs) and determine its underlying mechanisms, using a mouse model of optic nerve crush (ONC). METHODS: ONC was performed in the left eye of adult male mice, and the mice were randomly divided into minocycline-treated group and saline-treated control group. The mice without receiving ONC injury were used as positive controls. RGC densities were assessed in retinal whole mounts with immunofluorescence labeling of ßIII-tubulin. Transmission electron microscopy was used to detect RGC morphologies, and Western blotting and real-time PCR were applied to investigate the expression of autophagy markers LC3-I, LC3-II, and transcriptional factors nuclear factor-κB1 (NF-κB1), NF-κB2. RESULTS: In the early stage after ONC (at Days 4 and 7), the density of RGCs in the minocycline-treated group was higher than that of the saline-treated group. Electron micrographs showed that minocycline prevented nuclei and mitochondria injuries at Day 4. Western blotting analysis demonstrated that the conversion of LC3-I to LC3-II was reduced in the minocycline-treated group at Days 4 and 7, which meant autophagy process was inhibited by minocycline. In addition, the gene expression of NF-κB2 was upregulated by minocycline at Day 4. CONCLUSION: The neuroprotective effect of minocycline is generated in the early stage after ONC in mice, partly through delaying autophagy process and regulating NF-κB2 pathway.

Influence of mesenchymal stem cell transplantation on stereotypic behavior and dopamine levels in rats with Tourette syndrome.

CONTEXT: Tourette syndrome (TS) is a heterogeneous neuropsychiatric disorder. Chronic motor and phonic tics are central symptoms in TS patients. For some patients, tics are intractable to any traditional treatment and cause lifelong impairment and life-threatening symptoms. New therapies should be developed to address symptoms and overt manifestations of TS. Transplantation of neurogenic stem cells might be a viable approach in TS treatment. OBJECTIVE: We used mesenchymal stem cell (MSC) transplantation to treat TS. We discuss the mechanism of action, as well as the efficiency of this approach, in treating TS. SETTINGS AND DESIGN: An autoimmune TS animal model was adopted in the present study. Forty-eight Wistar rats were randomly allocated to the control group and the 2 experimental groups, namely, TS rats+vehicle and TS rats+MSC. MSCs were co-cultured with 5-bromodeoxyuridine (BrdU) for 24 h for labeling prior to grafting. METHODS: Stereotypic behaviors were recorded at 1, 7, 14, and 28 days after transplantation. Dopamine (DA) content in the striatum of rats in the 3 groups was measured using a high-performance liquid chromatography column equipped with an electrochemical detector (HPLC-ECD) on day 28 after transplantation. STATISTICAL ANALYSIS: Statistical analysis was performed by repeated measurements analysis of variance to evaluate stereotypic behavior counts at different time points. RESULTS: TS rats exhibited higher stereotypic behavioral counts compared with the control group. One week after transplantation, TS rats with MSC grafts exhibited significantly decreased stereotypic behavior. Rats with MSC grafts also showed reduced levels of DA in the striatum when compared with TS rats, which were exposed only to the vehicle. CONCLUSIONS: Intrastriatal transplantation of MSCs can provide relief from the stereotypic behavior of TS. Our results indicate that this approach may have potential for developing therapies against TS. The mechanism(s) of the observed effect may be related to the suppression of DA system by decreasing the content of DA in TS rats.