Transient versus prolonged hyperlocomotion following lateral fluid percussion injury in mongolian gerbils

Abstract

Posttraumatic hyperactivity is a neurobehavioral symptom commonly seen in patients after traumatic brain injury (TBI). No useful animal model has yet been established for evaluation of this important symptom. We induced either mild (MILD, 0.7-0.9 atm) or moderate (MOD, 1.3-1.6 atm) lateral fluid percussion injury (LFPI) in Mongolian gerbils. Open-field and T-maze tests were used during a 7-day period after the trauma. All animals were perfusion fixed for histopathological examinations. Transient locomotor hyperactivity was found with a peak at 6 hr after injury in the MILD animals, whereas MOD animals showed prolonged and severe hyperlocomotion throughout the 7-day posttrauma period (P < 0.0001). Interestingly, the temporal profile of the posttraumatic hyperactivity was similar to that of the working memory deficit in both injury groups. Histological examination revealed significant neural tissue damages, including cortical necrosis, white matter rarefaction, and neuronal loss in the hippocampus in the ipsilateral hemisphere of the MOD animals, vs. only negligible changes in the MILD animals. Correlation analysis revealed that the volume of white matter lesions was significantly correlated with both posttraumatic hyperactivity (r = 0.591, P < 0.01) and working memory deficit (r = -0.859, P < 0.0001). Taken together, our findings confirm the successful reproduction of posttraumatic hyperactivity following experimental TBI. The posttraumatic hyperlocomotion probably shared pathomechanisms common to those of cognitive dysfunction caused by LFPI, supporting the speculation from previous studies that some neurobehavioral abnormities intimately correlate with TBI-induced cognitive dysfunction. Histopathologically, significant involvement of white matter damage in the posttraumatic functional deficits was indicated.

Changes in mouse cognition and hippocampal gene expression observed in a mild physical- and blast-traumatic brain injury

“…These models employ stereotaxic instruments to induce a highly reproducible damage to a defined region of the brain dura (Abdel Baki et al, 2009; Li et al, 2006; McNamara et al, 2010; Sanders et al, 2001; Washington et al, 2012; Yu et al, 2009). While our model may lack injury reproducibility, compared to the FPI and CCI injury models, a main advantage of our model is that it is mild in nature and similar to the greatest injury prevalence clinically (De Kruijke et al, 2001).…”

Intensity of chronic cerebral hypoperfusion determines white/gray matter injury and cognitive/motor dysfunction in mice

“…In one traumatic brain injury model, WM injury induced persistent hyperlocomotion, and the severity of the WM lesions was correlated with the degree of locomotion (Li et al, 2006). The amygdala, the center of the anxiety pathway, receives input from the cerebral cortex and sends signals to the nucleus accumbens and the prefrontal cortex (Rosen, 2004).…”

Blockade of Acute Microglial Activation by Minocycline Promotes Neuroprotection and Reduces Locomotor Hyperactivity after Closed Head Injury in Mice: A Twelve-Week Follow-Up Study

“…It is worth noting that many neurological disorders and brain lesions, including TBI, can cause motor dysfunction such as locomotor hyperactivity (Li et al, 2006;Pullela et al, 2006;Viggiano, 2008). In this study, for the first time we used an automated actimeter to measure the spontaneous locomotor activity that occurs after TBI.…”