Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses.
Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. In the rat, enduring sensory sensitivity to whisker stimulation directs regional analysis to the whisker barrel circuit. Adult, male rats were subjected to midline fluid percussion brain or sham injury and evaluated between 1day and 42days post-injury. Whisker somatosensory regions of the cortex and thalamus maintained cellular composition as visualized by Nissl stain. Within the first week post-injury, quantitatively less cFos activation was elicited by whisker stimulation, potentially due to axotomy within and surrounding the whisker circuit as visualized by amyloid precursor protein immunohistochemistry. Over six weeks post-injury, cFos activation after whisker stimulation showed a significant linear correlation with time in the cortex (r(2)=0.545; p=0.015), non-significant correlation in the thalamus (r(2)=0.326) and U-shaped correlation in the dentate gyrus (r(2)=0.831), all eventually exceeding sham levels. Ongoing neuroplastic responses in the cortex are evidenced by accumulating growth associated protein and synaptophysin gene expression. In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity.
Hall
Kelley D
KD
Spinal Cord and Brain Injury Research Center, Chandler Medical Center, University of Kentucky, USA.
Lifshitz
Jonathan
J
D000818:Animals; D001930:Brain Injuries / Q000473:pathology / Q000503:physiopathology*; D019922:GAP-43 Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000502:physiology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology*; D016708:Synaptophysin / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014738:Vibrissae / Q000473:pathology / Q000502:physiology*
D019922:GAP-43 Protein; D016760:Proto-Oncogene Proteins c-fos; D016708:Synaptophysin