Objective: Traumatic brain injury (TBI) can result in motor and cognitive dysfunction and is a possible risk factor for the subsequent development of dementia. However, the pathogenesis of TBI remains largely unclear. This study investigated the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in inflammation and neuronal apoptosis following TBI.
Methods: The lncRNA expression profiles in the cerebral cortices of TBI model mice and sham-operated mice were analyzed using microarray. We focused on an upregulated lncRNA, PRR34-AS1, because of its known modulatory role in apoptosis and inflammation.
Results: Our findings indicated that the knockdown of PRR34-AS1 inhibited inflammation and neuronal apoptosis and improved long-term neurological function. Using an in vitro, cell-based model of etoposide-induced primary cortical neuronal injury, we demonstrated that PRR34-AS1 levels were higher in injured model cells than in untreated control cells. Silencing of PRR34-AS1 suppressed etoposide-induced apoptosis and the production of inflammatory mediators in primary cortical neurons. PRR34-AS1 directly targets microRNA-498 (miR-498) in primary cortical neurons. Importantly, the inhibition of miR-498 expression counteracted the effects of PRR34-AS1 silencing on neuronal apoptosis and inflammation.
Conclusions: These findings indicate that PRR34-AS1 may be a useful therapeutic target for TBI.
Keywords: MiR-498; PRR34-AS1; TBI; apoptosis; inflammation; neurological function; primary cortical neurons.