Mammalian Models of Traumatic Brain Injury and a Place for Drosophila in TBI Research

Abstract

Traumatic brain injury (TBI), caused by a sudden blow or jolt to the brain that disrupts normal function, is an emerging health epidemic with ∼2.5 million cases occurring annually in the United States that are severe enough to cause hospitalization or death. Most common causes of TBI include contact sports, vehicle crashes and domestic violence or war injuries. Injury to the central nervous system is one of the most consistent candidates for initiating the molecular and cellular cascades that result in Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). Not every TBI event is alike with effects varying from person to person. The majority of people recover from mild TBI within a short period of time, but repeated incidents can have deleterious long-lasting effects which depend on factors such as the number of TBIs sustained, time till medical attention, age, gender and genetics of the individual. Despite extensive research, many questions still remain regarding diagnosis, treatment, and prevention of long-term effects from TBI as well as recovery of brain function. In this review, we present an overview of TBI pathology, discuss mammalian models for TBI and focus on current methods using Drosophila melanogaster as a model for TBI study. The relatively small brain size (∼100,000 neurons and glia), conserved neurotransmitter signaling mechanisms and sophisticated genetics of Drosophila allows for cell biological, molecular and genetic analyses that are impractical in mammalian models of TBI.

Keywords: Drosophila; RNA-seq; behavioral genetics; neurogenetics; stress; traumatic brain injury.

FIGURE 1

Physical, behavioral, and cognitive effects of TBI.

FIGURE 2

Mammalian models of TBI. (A) Fluid percussion injury model: A rapid fluid pulse injection is used to cause injury directly onto the surface of the dura. (B) Controlled cortical impact model: Uses an electromagnetic device to permeate the brain at a known distance and velocity. (C) Weight-drop model: Releases a free weight directly onto the brain. (D) Blast injury model: Injury caused by primary injury of blast.

FIGURE 3

Drosophila models of TBI. (A) High-impact trauma (HIT) device: A spring attached to the wooden board on one end and a vial of flies attached to other. The vial is plugged with a cotton ball pushed deeper into the vial. The spring is deflected and released to inflict trauma to the flies when it hits the styrofoam pad. (B) Homogenizer model of TBI: Flies are placed in 2 ml screw cap tubes and placed in homogenizers at required speed for mild or severe TBI. (C) dCHI model of injury: A metal block moves forward due to the released current from the magnetic coil of the solenoid and hits the fly on top of the head.