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Objective To investigate the role of Toll-like receptor 4 (TLR4) in early brain injury in rats with subarachnoid hemorrhage and its effect on autophagy in hippocampus CA1 area. Methods Totally 192 SD rats were randomly divided into sham operation group, SAH model group (model group), SAH+DMSO solvent group (solvent group), and SAH+TLR4 inhibitor group (CLI-095 group). Each group was divided into 24h and 48h 2 time points. The SAH model was established by internal carotid artery puncture. The drug-administered group was injected with 10μL of DMSO solution or 100μg/mL of CLI-095 solution of 10μL before the preparation of SAH model. The behavioral changes of the rats were detected by Garcia score; the cerebral edema was detected by wet and dryweight method. The morphology of hippocampal CA1 neurons was observed by HE staining. Immunohistochemistry and immunoblotting were used to detect the expressions of TLR4, LC3 and Beclin1 in the hippocampus CA1 area. Results Compared with the sham group, Garcia score was reduced at each time point (P<0.05). The degree of brain edema was increased and the number of viable neurons was reduced (P<0.05). The expressions of TLR4, LC3 and Beclin1 were increased in the hippocampus CA1 area in the model group (P<0.05). Compared with the model group, the Garcia score was increased at each time point (P<0.05). The degree of brain edema was reduced and the number of viable neurons was increased (P<0.05). The expressions of TLR4, LC3 and Beclin1 were reduced in the hippocampus CA1 area in the CLI-095 group (P <0.05). Conclusion TLR4 may participate in the regulation of SAH-induced autophagy and aggravate the process of secondary brain injury in SAH. [ABSTRACT FROM AUTHOR]

Objective To explore the regulation of PI3K-mTOR signaling pathways on autophagy of hippocampus nerve cells after subarachnoid hemorrhage(SAH)in rats.Methods We randomly divided 72 male Sprague-Dawley rats into sham group,SAH model group and LY294002 group with 24 rats in each group.We established SAH model with the secondary injection of blood method while the sham group was not injected with blood.PI3 K signaling pathways specific inhibitor LY294002 was injected with 500μmol per rat 30 minutes before modeling.After 6,24,72 and 144 h morphologic changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of PI3 K,mTOR,Beclin-1 and LC3-II were detected by immunohistochemical method.Results The density of survival neurons in the SAH group was significantly lower than that in the control group(P<0.05),PI3K-mTOR signaling pathways were activated obviously,and the expressions of Beclin 1 and LC3-II were significantly higher than those in the control group(P <0.05).The number of survival neurons significantly decreased in the LY294002 group compared with the SAH group at each time point(P<0.05),PI3 KmTOR signaling pathways were suppressed.The expressions of Beclin-1 and LC3-II were significantly lower than those in the SAH group(P<0.05).Conclusion PI3K-mTOR signaling pathways protect neurons by activating the autophagy of neurons after SAH. [ABSTRACT FROM AUTHOR]

Objective To explore role of U0126, the specific inhibitor of ERK signaling pathway, in early brain injury (EBI) and the autophagy of nerve cells in hippocampus area in subarachnoid hemorrhage (SAH). Methods A total of 48 male adult SD rats were randomly divided into control group, SAH group, DMSO+SAH group, and U0126+SAH group, with 12 in each. We established SAH rat model by the puncture of internal carotid artery. The same amount of saline water, DMSO and U0126 solution of 0.5mL per rat was injected respectively into the rats of different groups 30min before modeling. The rats were killed at 24h. To measure brain water content by Wet and dry method after 24h, the morphological changes of hippocampus CA1 neural cells were observed by microscopy; the expression levels of ERK, Beclin-1 and LC3 were detected by using munohistochemical method. Results Compared with that in sham group, brain water content increased obviously in SAH model group. The density of surviving neurons in SAH group was significantly lower than that in control group (P<0.05). ERK signaling pathway was activated obviously, the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in control group (P<0.05). Compared with SAH model group, in U0126 group brain water content increased obviously. Compared with those in SAH group, the density of surviving neurons was significantly lower (P<0.05), ERK signaling pathway was suppressed, the expressions of Beclin-1 and LC3-Ⅱ were significantly lower (P<0.05). Conclusion The U0126, the ERK signaling pathway inhibitor, can inhibit neuron autophagy and increase EBR of SAH. [ABSTRACT FROM AUTHOR]