Multi-Modal Approach for Investigating Brain and Behavior Changes in an Animal Model of Traumatic Brain Injury

Abstract

Use of novel approaches in imaging modalities is needed for enhancing diagnostic and therapeutic outcomes of persons with a traumatic brain injury (TBI). This study explored the feasibility of using functional magnetic resonance imaging (fMRI) in conjunction with behavioral measures to target dynamic changes in specific neural circuitries in an animal model of TBI. Wistar rats were randomly assigned to one of two groups (traumatic brain injury/sham operation). TBI rats were subjected to the closed head injury (CHI) model. Any observable motor deficits and cognitive deficits associated with the injury were measured using beam walk and Morris water maze tests, respectively. fMRI was performed to assess the underlying post-traumatic cerebral anatomy and function in acute (24 hours after the injury) and chronic (7 and 21 days after the injury) phases. Beam walk test results detected no significant differences in motor deficits between groups. The Morris water maze test indicated that cognitive deficits persisted for the first week after injury and, to a large extent, resolved thereafter. Resting state functional connectivity (rsFC) analysis detected initially diminished connectivity between cortical areas involved in cognition for the TBI group; however, the connectivity patterns normalized at 1 week and remained so at the 3 weeks post-injury time point. Taken together, we have demonstrated an objective in vivo marker for mapping functional brain changes correlated with injury-associated cognitive behavior deficits and offer an animal model for testing potential therapeutic interventions options.

Dynamic resting state functional connectivity in awake and anesthetized rodents

“…Our data clearly showed that RSFC is intrinsically dynamic in the rat brain. These results are not only useful for understanding neural networks in animals at basal conditions, but also pave the way for further investigating their dynamic reconfigurations in different animal models of brain disorders (Heffernan et al, 2013; Huang et al, 2011; Liang et al, 2014). Therefore, we might be in a better position to translate findings between animals and humans.…”

Neuroplasticity to a single-episode traumatic stress revealed by resting-state fMRI in awake rats

“…However, this imaging technique has not been as commonly used in assessing different animal models for mental disorders (Heffernan et al, 2013; Huang et al, 2011). A major factor that precludes the applicability of rsfMRI methods in animal models involves the compounding effects of anesthetic agents used in most animal experiments on intrinsic FC.…”

A Novel Closed-Head Model of Mild Traumatic Brain Injury Using Focal Primary Overpressure Blast to the Cranium in Mice

“…12,20,29,[35][36][37][38][39][135][136][137][138][139] These models avoid the severe brain injury of open-skull models and the contributions of injury to other parts of the head or body that occur in a whole head or whole body blast model. The severity of the TBI with both the weight-drop and impactor approaches can be adjusted by changing the height of the weight drop or the impactor force, and the concussive impact can be delivered to different parts of the cranium to explore regional differences in TBI effects.…”

“…35,[37][38][39][133][134][135][136]138,139,[141][142][143][144][145][146][147][148] For example, rotarod deficits and axon injury have been reported after weightdrop TBI. 141,149 A more detailed review of functional deficits and brain pathology after TBI created by impact or weight drop on a closed skull has been provided by others.…”