Patients with type Ⅱ neurofibromatosis often have multiple neurological tumors, including schwannoma, meningioma, astrocytoma and ependymoma, of which bilateral vestibular schwannoma is characteristic lesion. More than 90％of familial cases and 80％-85％of sporadic cases of type Ⅱ neurofibromatosis have been confirmed to have neurofibromatosis Ⅱ gene mutations in both tumor tissues and blood. This article reviews the relation of type Ⅱ neurofibromatosis with different types of tumors, and the incidence, natural history and latest treatment strategies of type Ⅱ neurofibromatosis, in order to provide new clues for diagnoses and treatments of patients with type Ⅱ neurofibromatosis complicated with multi-type tumors.

Objective To investigate the proliferative capacity of neural stem cells (NSCs) in rat hippocampus after traumatic brain injury (TBI) and its relationship with Janus kinase 2/signaling and transcriptional activation factor 3 (JAK2/STAT3) signaling pathway activity.Methods A total of 108 SD rats were randomly divided into control group (36 rats) and TBI group (72 rats).The TBI model was constructed by PinPointTM Precision Cortical Impactor.At 1,3,7,14,21 and 28 days after injury,the brain tissues were taken for immunofluorescence staining to detect the proliferation of NSCs [5-bromodeoxyuridine (BrdU) +/stem cell key protein-2 (Sox2) +] in hippocampus,and phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were detected by Western blot.The expression level of p-JAK2 and p-STAT3 as well as the changing trend were analyzed.On the basis of preliminary analysis of the proliferation of NSCs and the change of JAK2/STAT3 signaling pathway activity in hippocampus,another 24 SD rats were randomly divided into TBI + normal saline group and TBI +AG490 (JAK2 specific inhibitor) group,with 12 rats in each group.At 7 days after injury,the proliferation of NSCs in hippocampus was detected by immunofluorescence staining,and the expression levels of p-JAK2 and p-STAT3 were detected by Western blot,so as to further confirm the correlation between the proliferation ability of NSCs in hippocampus and JAK2/STAT3 signaling pathway.Results Compared with the control group,the number of NSCs in the hippocampus of the TBI group and the expression of p-JAK2 and p-STAT3 increased.And the most significant increase occurred at 7 days after injury [number of NSCs:31.2 ± 4.7 in the control group,111.4 ± 8.1 in the TBI group (P ＜ 0.01);p-JAK2:1.11 ± 0.09 in the control group,2.16 ± 1.01 in the TBI group (P ＜ 0.01);p-STAT3:1.05 ± 0.06 in the control group and 2.06 ± 0.09 in the TBI group (P ＜ 0.01)].The proliferation of NSCs in hippocampus of TBI group was consistent with the change of p-JAK2 and p-STAT3 expression.Seven days after injury,the expression levels of p-JAK2 and p-STAT3 and the proliferation ability of NSCs in the TBI + AG490 were significantly decreased [p-JAK2:2.18 ± 0.15 in the TBI + isotonic saline group,1.24 ±0.10 in the TBI + AG490 group (P ＜0.01);p-STAT3:2.21 ±0.12 in the TBI + isotonic saline group,1.25 ± 0.11 in the TBI + AG490 group (P ＜ 0.01);NSCs number:112.8 ± 8.6 in the TBI + isotonic saline group,75.5 ± 6.4 in the TBI + AG490 group (P ＜ 0.05)].Conclusions The proliferation of NSCs in hippocampus of rats increased after TBI,and the activity of JAK2/STAT3 signaling pathway also increased,following the same trend.JAK2 inhibitor AG490 can reduce the activity of JAK2/STAT3 signaling pathway and the proliferation of NSCs.This can provide reference for researches on TBI promoting nerve regeneration and function repair.

Objective To explore the influence of exosome-derived miR-124 on the molecular expression related to axonal regeneration after mechanical damage to cortical neurons in mice,aiming to provide experimental data for intervention in neurogenesis after traumatic brain injury (TBI).Methods The plasmid loaded with miR-124 was used to transfect the HEK293 cell line.The transfection effect was identified by real time Polymerase Chain Reaction (qPCR).The exosomes were isolated from the supematant of cultured transfected HEK293 cell line by the SBI isolation kit.The isolated exosomes were identified by electron microscopy and Western blotting,and the involved miR-124 in the exosomes was identified by qPCR.After the cortical neurons were isolated from the pregnant mice (14-17-day old) and cultured for 7 days,they were divided into 4 groups:control,damage,damage + exosomes without miR-124 and damage + exosomes with miR-124.The Petri dishes were manually scratched with a 10 μL plastic stylet needle to construct a mechanical damage in vitro in the latter 3 groups.The isolated exosomes without or with miR-124 were added into the cultured medium for culture for 72 h in the latter 2 groups,respectively.The expression ofmiR-124,NRP-1,Tau and Gap-43 was measured by qPCR and Western blotting respectively.Results The exosomes containing miR-124 were successfully obtained by plasmid transfection and the SBI isolation kit.The expression levels of miR-124,NRP-1 and Gap-43 in the damage + exosomes with miR-124 group were elevated significantly greater than in the other 3 groups (P＜0.05).The expression levels ofmiR-124,NRP-1 and Gap-43 in the damage group and damage + exosomes without miR-124 group were elevated significantly greater than in control group (P＜0.05).Conclusions The exosomes may transmit miR-124 to the cortical neurons in mice after mechanical damage and increase the expression ofmiR-124,NRP-1 and Gap-43 in the cortical neurons in mice.

Objective To explore the effect of exosome derived micro RNA (miR)-124 on activation status of microglia cells in injured brain tissues at acute phase of traumatic brain injury (TBI), and further provide theoretical references for intervention of neuroinflammation after TBI. Methods (1) In vitro cultured HEK293 cells were divided into miR-124 transfected group and control group, and miR-124 plasmids or Control siRNA by plasmid were transfected into the cells of the two groups;two-three weeks after isolation of monoclonal cell lines and two weeks after continuous culture, reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the miR-124 content in cells of the two groups; the exosomes were extracted from the supernatant of cells from the two groups using SBI kit, and the morphology of the exosomes was observed under electron microscope; the expression of CD63, a surface marker molecule, was detected by Western blotting; RT-PCR was used to determine the miR-124 content in the exosomes of the two groups. (2) A total of 60 healthy male rats were randomly divided into sham-operated group (n=12), TBI group (n=12) and TBI+Exo-124 group (n=24); TBI models were constructed by controlled cortical injury device, and Exo-124 (3×109 particles) was given into the TBI+Exo-124 group via tail intravenous injection and equivalent solvent was given to the sham-operated group and TBI group 24 h after TBI; 3 d after modeling, RT-PCR was used to detect the miR-124 expression in brain tissues of the injured areas of the three groups; flow cytometry (FCM) was used to detect the percentages of Iba-1+/CD32+ and Iba-1+/CD206+ microglial cells in brain tissues; enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of interleukin (IL)-1, IL-6, IL-4 and IL-10 in the brain tissues. Results (1) RT-PCR showed that the miR-124 expression in the miR-124 transfected group was statistically higher than that in the control group (P<0.05); electron microscopy showed spherical particles with diameter about 100 nm and obvious membrane structure; Western blotting showed that the expression level of CD63 in the miR-124 transfected group was significantly higher than that in the control group (P<0.05); RT-PCR showed that the miR-124 content in the miR-124 transfected group was significantly higher than that in the control group (P<0.05). (2) The miR-124 expression in injured brain tissues of TBI+Exo-124 group was statistically higher than that in TBI group and sham-operated group (P<0.05); as compared with those in the sham-operated group, the percentages of Iba-1+/CD32+ and Iba-1+/CD206+ microglial cells and the expressions of IL-1, IL-6, IL-4 and IL-10 in the brain tissues of TBI group were significantly increased (P<0.05); as compared with the TBI group, the TBI+Exo-124 group had significantly decreased percentage of Iba-1+/CD32+ microglial cells and significantly increased percentage of Iba-1+/CD206+ microglial cells, statistically decreased IL-1 and IL-6 expressions, and statistically increased IL-4 and IL-10 expressions (P<0.05). Conclusion Exosome-derived miR-124 promotes the polarization of microglia cells from M1 to M2 and reduces neuroinflammation at acute phase of TBI.