Ketamine administration causes cognitive impairment by destroying the circulation function of the glymphatic system.

BACKGROUND: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. METHODS: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. RESULTS: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5' regulatory region of the Aqp4 gene (-1096 bp to -1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. CONCLUSIONS: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.

The preparation and characterization of liquefied wood based primary fibers.

The preparation of primary fibers were performed from liquefied wood in phenol by melt-spinning with different spinnerettes of length/diameter ratio (L/D) (0, 2, and 4), to investigate the effect of the size of spinnerette on the thermal stability and structural properties of primary fibers. High thermal transition temperatures and small weight loss percentages of resultant primary fibers representing good thermal stability were obtained with L/D of spinnerette increasing. Besides, few defective structure occurred on cross section and surface of primary fibers in comparison with those prepared with spinnerette of L/D=0. We found that these improvements were caused by the formation of hydrogen bond among phenolic hydroxyl groups in the period of flow entering the cylindrical die of spinnerette. Thus, the precursor, with either porous structure for preparing activated carbon fibers or defect-free structure for preparing carbon fibers with high performance, can be probably prepared by controlling the spinnerette system.