Hepatocyte Growth Factor/MET Activator Rescues Working Memory Deficits after Repeated Mild Traumatic Brain Injury.

Preclinical animal study using a closed-head midline impact model of mild traumatic brain injury in rats

“Using a closed-head midline impact model of mild TBI, we characterized the actions of the HGF/MET system on working memory performance after repeated injury.”

Male and female Long-Evans rats

“Male (n = 33) and female (n = 19) Long-Evans rats were single-housed with enrichment on a 12/12-h reverse light cycle”

52 rats (33 males and 19 females)

“Male (n = 33) and female (n = 19) Long-Evans rats were single-housed with enrichment on a 12/12-h reverse light cycle”

Repeated surgeries over 1 week followed by 5 days of behavioral testing

“A reverse light cycle ensured that repeated sham or closed-head mTBI surgeries (n = 3 over 1 week) and training/testing the working memory task28–30 occurred during their active period (Fig. 1A).”

Repeated mild TBI significantly impaired working memory performance compared to baseline and sham-injured animals

“Repetitive mild TBI significantly impaired performance from baseline (Fig. 1. ANOVA(injury) F(2,136) = 14.4199, p < 0.0001; HSD, p < 0.0001, 67.1% correct) and from sham-injured animal performance (HSD, p = 0.0159).”

The procognitive effects of dihexa were blocked by pretreatment with the MET antagonist Hinge

“Pretreatment with the MET antagonist, Hinge (KYRDIN, 300 pmol) significantly blocked the procognitive effects of dihexa (1 nmol/day, 68.6%, HSD p < 0.0001).”

The study design and analytic plan were not preregistered

“The study design and analytic plan were not preregistered.”