Traumatic Brain Injury

NKILA[LncRNA]

mir-195[miRNA]

NLRX1[mRNA]

Neurons

Homo sapiens (human)

Aging (Albany NY). 2021 Mar 3;13(6):8127-8145. doi: 10.18632/aging.202618. Epub 2021 Mar 3.

Long noncoding RNA NKILA transferred by astrocyte-derived extracellular vesicles protects against neuronal injury by upregulating NLRX1 through binding to mir-195 in traumatic brain injury.

RACE;

The study aims to investigate the effects of long noncoding RNA (lncRNA) transmitted nuclear factor-kB interacting lncRNA (NKILA)-containing astrocyte-derived small extracellular vesicles (EVs) on traumatic brain injury (TBI). TBI was modeled in vitro by exposing human neurons to mechanical injury and in vivo by controlled cortical impact in a mouse model. The gain- and loss-function approaches were conducted in injured neurons to explore the role of NKILA, microRNA-195 (miR-195) and nucleotide-binding leucine-rich repeat containing family member X1 (NLRX1) in neuronal injury. EVs extracted from NKILA-overexpressing astrocytes were used to treat injured neurons. It was revealed that NKILA was downregulated in injured neurons. Astrocyte co-culture participated in the upregulation of NKILA in injured neurons. Additionally, NKILA could competitively bind to miR-195 that directly targeted NLRX1. Next, the upregulation of NLRX1 or NKILA relived neuronal injury by promoting neuronal proliferation but inhibiting apoptosis. Astrocyte-derived EVs transferred NKILA into neurons, which led to the downregulation of miR-195, upregulation of NLRX1, increased cell proliferation, and decreased cell apoptosis. The in vivo experiments validated that NKILA-containing EVs promoted brain recovery following TBI. Collectively, astrocyte-derived EVs carrying NKILA was found to alleviate neuronal injury in TBI by competitively binding to miR-195 and upregulating NLRX1.