Biomechanical induction of mild brain trauma in larval zebrafish: effects on visual startle reflex habituation

Abstract

A mild Traumatic Brain Injury is a neurological disturbance of transient or/and chronic nature after a direct blow of the head/neck or exposure of the body to impulsive biomechanical forces, indirectly affecting the brain. The neuropathological events leading to the clinical signs, symptoms and functional disturbances are still elusive due to a lack of sensitive brain-screening tools. Animal models offer the potential to study neural pathomechanisms in close detail. We recently proposed a non-invasive protocol for inducing concussion-like symptoms in larval zebrafish via exposure to rapid linearly accelerating-decelerating body motion. By mean of auditory startle reflex habituation assessments – an established neurophysiological health index – we probed acute and chronic effects which mirror human concussion patterns. This study aimed at expanding our previous work by assessing the ensuing effects with visual – as opposed to auditory – startle reflex habituation quantifications, by using the same methodology. We observed that immediately after impact exposure, the fish showed impaired sensory reactivity and smaller decay constant, possibly mirroring acute signs of confusion or loss of consciousness in humans. By 30-min post-injury, the fish display temporary signs of visual hypersensitivity, manifested as increased visuomotor reactivity and a relatively enlarged decay constant, putatively reflecting human post-concussive sign of visual hypersensitivity. In the following 5-24 hours, the exposed fish progressively develop chronic signs of CNS dysfunction, in the form of low startle responsivity. However, the preserved decay constant suggests that neuroplastic changes may occur to restore CNS functioning after undergoing the “concussive procedure”. The observed findings expand our previous work providing further behavioural evidence for the model. Limitations that still require addressment are discussed, advancing further behavioural and microscopic analyses which would be necessary for the validation of the model in its putative relatability with human concussion.