Gamma frequency entrainment rescues cognitive impairment by decreasing postsynaptic transmission after traumatic brain injury

Introduction

The relationship between oscillatory activity in hippocampus and cognitive impairment in traumatic brain injury (TBI) remains unclear. Although TBI decreases gamma oscillations and 40 Hz light flicker improves TBI prognosis, the effects and mechanism of rhythmic flicker on TBI remain unclear.

Aims

In this study, we aimed to explore whether light flicker could reverse cognitive deficits, and further explore its potential mechanisms in TBI mouse model.

Methods

The Morris water maze test (MWM), step-down test (SDT), and novel object recognition test (NOR) were applied to evaluate the cognitive ability. The local field potential (LFP) recording was applied to measure low gamma reduction of CA1 in hippocampus after TBI. And electrophysiological experiments were applied to explore effects of the gamma frequency entrainment on long-term potentiation (LTP), postsynaptic transmission, and intrinsic excitability of CA1 pyramidal cells (PCs) in TBI mice. Immunofluorescence staining and western blotting were applied to explore the effects of 40 Hz light flicker on the expression of PSD95 in hippocampus of TBI mice.

Results

We found that 40 Hz light flicker restored low gamma reduction of CA1 in hippocampus after TBI. And 40 Hz, but not random or 80 Hz light flicker, reversed cognitive impairment after TBI in behavioral tests. Moreover, 40 Hz light flicker improved N-methyl-D-aspartate (NMDA) receptor-dependent LTP (LTP_NMDAR) and L-type voltage-gated calcium channel-dependent LTP (LTP_L-VGCC) after TBI treatment. And gamma frequency entrainment decreased excitatory postsynaptic currents (EPSCs) of CA1 PCs in TBI mice. Our results have illustrated that 40 Hz light flicker could decrease intrinsic excitability of PCs after TBI treatment in mice. Furthermore, 40 Hz light flicker decreased the expression of PSD95 in hippocampus of TBI mice.

Conclusion

These results demonstrated that 40 Hz light flicker rescues cognitive impairment by decreasing postsynaptic transmission in PCs after TBI treatment in mice.     

Haematopoietic stem cell transplantation for hepatitis-associated aplastic anaemia and non-hepatitis-associated aplastic anaemia: A propensity score-matched analysis

To validate the efficacy and safety of haematopoietic stem cell transplantation (HSCT) in hepatitis-associated aplastic anaemia (HAAA) patients, we reviewed 260 patients who underwent HSCT for acquired aplastic anaemia and eventually included 30 HAAA patients and 90 non-HAAA patients using propensity score matching. In the HAAA group, the estimated 5-year overall survival rate (75.8% vs. 86.5%, p = 0.409), failure-free survival (FFS) rate (74.0% vs. 83.2%, p = 0.485), graft-versus-host disease (GVHD)-free FFS rate (61.2% vs. 67.6%, p = 0.669) after HSCT were slightly lower but not statistically significant than those in the non-HAAA group. Both groups did not significantly differ in engraftment, post-transplant severe infection, cytomegalovirus (CMV) or Epstein-Barr virus viraemia, or GVHD incidences. The patterns of immune reconstitution were broadly consistent between the two groups. When stratifying HAAA patients according to donor type, no significant differences in survival, transplant-related mortality, or GVHD cumulative incidences were observed. CMV viraemia (68.7% vs 8.3%, p = 0.009) occurred more commonly in haploidentical donor (HID) transplants than in matched sibling donor transplants. However, early CMV disease incidence (5.6% vs. 0.0%, p = 1.000) was low. Overall, the post-transplant outcomes of HAAA patients were comparable to those of non-HAAA patients after balancing potential confounders, and HID-HSCT can offer an alternative curative option for HAAA.     

Is Patient-Specific Instrumentation Accurate and Necessary for Open-Wedge High Tibial Osteotomy? A Meta-Analysis

The purpose of this meta-analysis was to identify if patient-specific instrumentation (PSI) could increase the accuracy of the correction in high tibial osteotomy (HTO) and to explore the assessment indices and the necessity of using a PSI in HTO. A systematic search was carried out using online databases. A total of 466 patients were included in 11 papers that matched the inclusion criteria. To evaluate the accuracy of PSI-assisted HTO, the weight bearing line ratio (WBL%), hip-knee-ankle angle (HKA), mechanical medial proximal tibial angle (mMPTA), and posterior tibial slope angle (PTSA) were measured preoperatively and postoperatively and compared to the designed target values. Statistical analysis was performed after strict data extraction with Review Manager (version 5.4). Significant differences were detected in WBL% (MD = −36.41; 95% CI: −42.30 to −30.53; p < 0.00001), HKA (MD = −9.95; 95% CI: –11.65 to –8.25; p < 0.00001), and mMPTA (MD = –8.40; 95% CI:−10.27 to −6.53; p < 0.00001) but not in PTSA (MD = 0.34; 95% CI: −0.59 to 1.27; p = 0.47) between preoperative and postoperative measurements. There was no significant difference between the designed target values and the postoperative correction values of HKA (MD = 0.14; 95% CI: −0.19 to 0.47; p = 0.41) or mMPTA (MD = 0.11; 95% CI −0.34 to 0.55; p = 0.64). The data show that 3D-based planning of PSI for HTO is both accurate and safe. WBL%, HKA, and mMPTA were the optimal evaluation indicators of coronal plane correction. Sagittal correction is best evaluated by the PTSA. The present study reports that PSI is accurate but not necessary in typical HTO.