EPPS treatment attenuates traumatic brain injury in mice by reducing A β burden and ameliorating neuronal autophagic flux.

EPPS treatment attenuates traumatic brain injury in mice by reducing Aβ burden and ameliorating neuronal autophagic flux.
Exp Neurol. 2019 Jan 09;:
Authors: Anthony Jalin AMA, Jin R, Wang M, Li G
Abstract
Beta-amyloid (Aβ) burden and impaired neuronal autophagy contribute to secondary brain injury after traumatic brain injury (TBI). 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS) treatment has been reported to reduce Aβ aggregation and rescue behavioral deficits in Alzheimer's disease-like mice. Here, we investigated neuroprotective effects of EPPS in a mouse model of TBI. Mice subjected to controlled cortical impact (CCI) were treated with EPPS (120 mg/kg, orally) immediately after CCI and thereafter once daily for 3 or 7 days. We found that EPPS treatment profoundly reduced the accumulation of beta-amyloid precursor protein (β-APP) and Aβ over a widespread area detected in the pericontusional cortex, external capsule (EC), and hippocampal CA1 and CA3 at 3 days after TBI, accompanied by significant reduction in the TBI-induced diffuse axonal injury identified by increased immunoreactivity of SMI-32 (an indicator for axonal damage). We also found that EPPS treatment ameliorated the TBI-induced synaptic damage (as reflected by enhanced postsynaptic density 95, PSD-95), and impairment of autophagy flux in the neurons as reflected by reduced autophagy markers (LC3-II/LC3-I ratio and p62/SQSTM1) and increased lysos...

Source: Experimental Neurology - January 9, 2019 Category: Neurology Authors: Anthony Jalin AMA, Jin R, Wang M, Li G Tags: Exp Neurol Source Type: research