Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: Evaluation by conditioned fear response

Abstract

Conditioned fear associates a contextual environment and cue stimulus to a foot shock in a single training trial, where fear expressed to the trained context or cue indicates cognitive performance. Lesion, aspiration or inactivation of the hippocampus and amygdala impair conditioned fear to the trained context and cue, respectively. Moreover, only bilateral experimental manipulations, in contrast to unilateral, abolish cognitive performance.In a model of unilateral brain injury, we sought to test whether a single lateral fluid percussion brain injury impairs cognitive performance in conditioned fear. Brain-injured mice were evaluated for anterograde cognitive deficits, with the hypothesis that acute injury-induced impairments improve over time. Male C57BL/6J mice were brain-injured, trained at five or 27 days post-injury, and tested 48 hours later for recall of the association between the conditioned stimuli (trained context or cue) and the unconditioned stimulus (foot shock) by quantifying fear-associated freezing behavior. A significant anterograde hippocampal-dependent cognitive deficit was observed at seven days in brain-injured compared to sham. Cued fear conditioning could not detect amygdala-dependent cognitive deficits after injury and stereological estimation of amygdala neuron number corroborated this finding. The absence of injury-related freezing in a novel context substantiated injury-induced hippocampal-dependent cognitive dysfunction, rather than generalized fear. Variations in the training and testing paradigms demonstrated a cognitive deficit in consolidation, rather than acquisition or recall. By one month post-injury, cognitive function recovered in brain-injured mice. Hence, the acute injury-induced cognitive impairment may persist while transient pathophysiological sequelae are underway, and improve as global dysfunction subsides.

Dietary branched chain amino acids ameliorate injury-induced cognitive impairment

“…Lateral fluid percussion injury (LFPI) reproducibly damages this structure, and causes cognitive impairment (3,4) and regional shifts in network excitability in both area CA1 (decreased net synaptic efficacy) and dentate gyrus (increased net synaptic efficacy) (4)(5)(6)(7).…”

Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice

“…Thus, even mildly injured mice are less efficient than the sham mice at using external cues to process, consolidate, and store spatial information, which must be retrieved during subsequent testing. Other hippocampal-dependent cognitive tasks such as conditioned fear response have been shown to be impaired in mice subjected to LFP 26 . Finally, the shorter latency to fall by LFP mice relative to sham mice in the rotarod paradigm up to 3 weeks following mild injury is an indicator of deficits in integrated vestibulomotor and sensorimotor function.…”

Early and Persistent Dendritic Hypertrophy in the Basolateral Amygdala following Experimental Diffuse Traumatic Brain Injury

“…Previous experiments demonstrated no loss of neurons in the BLA at PID7 or 30 after lateral FPI in the mouse. 43 Another study failed to detect degenerating neurons in the amygdala by Fluoro-Jade staining in the subacute phase (PID1, 2, and 7) post-FPI or weight drop experimental TBI. 44 However, the increase of GFAP immunoreactivity in the absence of a destructive lesion or neuropathology can indicate astrocytic support of neuritic extension and axon regeneration through expression of a subset of surface molecules and neurotrophic factors.…”