Releasing of Herpes Simplex Virus Carrying NGF in Subarachnoid Space Promotes the Functional Repair in Spinal Cord Injured Rats.
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BACKGROUND: Spinal cord injury (SCI) is a serious disease which can lead to bad consequence in patients. Gene therapies, as an effective strategy, have been developed for the treatment of several diseases. But the effect for the treatment of SCI is also waiting to be practiced. OBJECTIVE: Here, we explored the effect of NGF administration carried by herpes simplex virus (HSV) in the injured spinal cord. METHODS: Transgenic recombinant containing human NGF was constructed by using pSP72 plasmid, then enveloped by non-replication HSV vector with deleted ICP27, ICP4 and ICP34.5 genes. Next, HSV recombinant carrying NGF was injected into cerebrospinal fluid in the lumbar cord to detect the effect of NGF for the improvement of motor function, indicated by BBB score. Meanwhile, IHC, QPCR and WB were used to confirm the NGF transduction. RESULTS: After SCT, BBB score was largely decreased, followed by a gradual limit recovery with time going on. Q-PCR confirmed that the mRNA expression of NGF was increased in the spinal cord at 28 days post-operation, compared with that in the sham group, which suggests endogenous NGF may be available to the limit repair of motor function. Moreover, HSV carried NGF was injected into subarachnoid space of the spinal cord, which results in a significant functional improvement in hindlimbs from 7dpo to 49dpo. The level of NGF in HSV-NGF administrated group was obviously higher than that in the empty vector group and SCT group, only. CONCLUSION: Our results demonstrate that releasing of HSV-NGF-recombinant in subarachnoid space, can effectively improve the motor function in hindlimbs of rats subjected to SCT, which supports that strategy of HSV carrying NGF may be used for the treatment of SCI in future clinic practice.
