MMP-9 Contributes to Dendritic Spine Remodeling Following Traumatic Brain Injury.

Barbara Pijet,Marzena Stefaniuk,Leszek Kaczmarek

doi:10.1155/2019/3259295

Abstract

Traumatic brain injury (TBI) occurs when a blow to the head causes brain damage. Apart from physical trauma, it causes a wide range of cognitive, behavioral, and emotional deficits including impairments in learning and memory. On neuronal level, TBI may lead to circuitry remodeling and in effect imbalance between excitatory and inhibitory neurotransmissions. Such change in brain homeostasis may often lead to brain disorders. The basic units of neuronal connectivity are dendritic spines that are tiny protrusions forming synapses between two cells in a network. Spines are dynamic structures that undergo morphological transformation throughout life. Their shape is strictly related to an on/off state of synapse and the strength of synaptic transmission. Matrix metalloproteinase-9 (MMP-9) is an extrasynaptically operating enzyme that plays a role in spine remodeling and has been reported to be activated upon TBI. The aim of the present study was to evaluate the influence of MMP-9 on dendritic spine density and morphology following controlled cortical impact (CCI) as animal model of TBI. We examined spine density and dendritic spine shape in the cerebral cortex and the hippocampus. CCI caused a marked decrease in spine density as well as spine shrinkage in the cerebral cortex ipsilateral to the injury, when compared to sham animals and contralateral side both 1 day and 1 week after the insult. Decreased spine density was also observed in the dentate gyrus of the hippocampus; however, in contrast to the cerebral cortex, spines in the DG became more filopodia-like. In mice lacking MMP-9, no effects of TBI on spine density and morphology were observed.

Highlights

Traumatic brain injury caused by an external mechanical force evokes a variety of brain responses, including focal extrasynaptic matrix degradation, neuronal loss within hippocampus area, glia activation, synaptic remodeling, and ion channels activity changes [1, 2]
Decrease in Spine Density in the Cerebral Cortex and the Hippocampus Evoked by Controlled Cortical Impact (CCI)
Similar effect was observed in the dentate gyrus (DG) where 24 hours and 7 days after Traumatic brain injury (TBI) spine density were significantly lower compared to the contralateral side (24 h ∗P < 0 0001; 7 d ∗P = 0 0001; Figure 1(c)) and sham-operated animals (24 h ∗P = 0 0251; 7 d ∗∗∗∗P < 0 0001; Figure 1(c))

Summary

Introduction

Traumatic brain injury caused by an external mechanical force evokes a variety of brain responses, including focal extrasynaptic matrix degradation, neuronal loss within hippocampus area, glia activation, synaptic remodeling, and ion channels activity changes [1, 2]. A massive glutamate efflux, increased level of extracellular glutamate, and hyperactivation of NMDAR receptor channels followed by their loss are observed [3]. These events are strictly related to dendritic spine remodeling [4]. To what extent upon brain injury MMP-9 is involved in altering dendritic spines number and shape is yet unknown. To bridge this gap, we set out to analyze the effects of MMP-9 levels on TBIstimulated plastic changes of the dendritic spines in the mouse brain. We used controlled cortical impact (CCI) as an animal model of traumatic brain injury [46]

Objectives

Methods

Results

Discussion

Conclusion