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Traumatic brain injury (TBI) may cause neurological damage, but an effective therapy and the associated mechanisms of action have not yet been elucidated. A TBI model was established using the modified Feeney method. A2B5+ cells, an oligodendroglial progenitor, were acquired from induced pluripotent stem cells (iPSCs) by mouse embryonic fibroblasts and were transplanted into the injured site. The neurological severity score (NSS) was recorded on 3 d, 7 d, 11 d, 15 d, and 19 d. Seven days after transplantation, oligodendrocytes 2 (Olig2) and myelin basic protein (MBP) were detected by immunohistochemistry (IHC) and Western blot (WB), and long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) were screened by microarray technology. Moreover, we took an intersection of the differentially expressed lncRNAs or mRNAs and scanned 10 kb upstream and downstream of the common lncRNAs. Meanwhile, Gene Ontology (GO) and pathway analysis on mRNAs was performed in the A2B5+ iPSC group. A2B5+ iPSCs survived and migrated around the injury site and differentiated into oligodendrocytes. Meanwhile, the increase in Olig2 and MBP were higher in A2B5+ cell-engrafted rats than that in TBI rats. However, the NSSs in the A2B5+ iPSC group were lower than that in the TBI group. Between the TBI and sham groups, 270 lncRNAs and 1,052 mRNAs were differently expressed ( P < 0.05, fold change (FC) > 2), while between the A2B5+ iPSC and TBI groups, 83 lncRNAs and 360 mRNAs were differently expressed ( P < 0.05, FC > 2). Meanwhile, 37 lncRNAs and 195 mRNAs were simultaneously changed in the 2 parts. Using bioinformatic analysis, we found the crucial lncRNA and mRNA were ENSRNOT00000052577 and Kif2c in the TBI brain with cell transplantation. This study demonstrated that A2B5+ iPSC grafts effectively improved neurological function, and the mechanism of action was associated with lncRNA and mRNA expression. Therefore, A2B5+ iPSC transplantation could be considered as a new method for the treatment of TBI, and ENSRNOT00000052577 and Kif2c may be new molecular targets or markers for functional improvement.

To investigate the role of Trim32 in traumatic brain injury (TBI), adult male Sprague Dawley (SD) rats and mice were randomly divided into sham (n = 6) and TBI groups ( n = 24), respectively. Then, mice were assigned into Trim32 knockout mice (Trim32-KO [+/−]) and wild-type (WT) littermates. The TBI model used was the Feeney free-falling model, and neurological function was evaluated after TBI using a neurological severity score (NSS). Reverse transcription polymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry were used to investigate the expression of Trim32 in the damaged cortex. Cell apoptosis in the cortex was detected by terminal-deoxynucleoitidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Moreover, Trim32-KO (+/−) mice were used to determine the effect of Trim in neurological repair after TBI. Results showed the NSS scores in TBI rats were significantly increased from day 1 to day 11 postoperation, compared with the sham group. Trim32 messenger RNA (mRNA) expression in the cortex was significantly increased at 7 d after TBI, while the level of Tnr and cytochrome c oxidase polypeptide 5A mRNA didn’t exhibit significant changes. In addition, Western blot was used to detect the level of Trim32 protein in the cortex. Trim32 expression was significantly increased at 7 d after TBI, and immunoreactive Trim32-positive cells were mainly neurons. Moreover, Trim32-KO (+/−) mice with TBI had lower NSS scores than those in the WT group from day 1 to day 11 postoperation. Meanwhile, Trim32-KO (+/−) mice had a decreased number of TUNEL-positive cells compared with the control group at 3 d postoperation. Protein 73 (p73) decreased at 7 d postoperation in Trim32-KO (+/−) mice with TBI, when compared with WT mice with TBI. Our study is the first to confirm that suppression of Trim32 promotes the recovery of neurological function after TBI and to demonstrate that the underlying mechanism is associated with antiapoptosis, which may be associated with p73.

Traumatic brain injury (TBI) is a common disease that usually causes severe neurological damage, and current treatment is far from satisfactory. The neuroprotective effects of neural stem cell (NSC) transplantation in the injured nervous system have largely been known, but the underlying mechanisms remain unclear, and their limited sources impede their clinical application. Here, we established a rat model of TBI by dropping a weight onto the cortical motor area of the brain and explored the effect of engrafted NSCs (passage 3, derived from the hippocampus of embryonic 12- to 14-d green fluorescent protein transgenic mice) on TBI rats. Moreover, RT-PCR and Western blotting were employed to investigate the possible mechanism associated with NSC grafts. We found rats with TBI exhibited a severe motor and equilibrium dysfunction, while NSC transplantation could partly improve the motor function and significantly reduce cell apoptosis and increase B-cell lymphoma–extra large (Bcl-xL) expression at 7 d postoperation. However, other genes including Bax, B-cell lymphoma 2, Fas ligand, and caspase3 did not exhibit significant differences in expression. Moreover, to test whether Bcl-xL could be used as a therapeutic target, herpes simplex virus (HSV) 1 carrying Bcl-xL recombinant was constructed and injected into the pericontusional cortices. Bcl-xL overexpression not only resulted in a significant improvement in neurological function but also inhibits cell apoptosis, as compared with the TBI rats, and exhibits the same effects as the administration of NSC. The present study therefore indicated that NSC transplantation could promote the recovery of TBI rats in a manner similar to that of Bcl-xL overexpression. Therefore, Bcl-xL overexpression, to some extent, could be considered as a useful strategy to replace NSC grafting in the treatment of TBI in future clinical practices.