Neuropathology in sensory, but not motor, brainstem nuclei of the rat whisker circuit after diffuse brain injury

Abstract

Neurological dysfunction after traumatic brain injury (TBI) is associated with pathology in cortical, subcortical, and brainstem nuclei. Our laboratory has reported neuropathology and microglial activation in the somatosensory barrel cortex (S1BF) and ventral posterior medial thalamus (VPM) after diffuse TBI in the rat, which correlated with post-injury whisker sensory sensitivity. The present study extends our previous work by evaluating pathology in whisking-associated sensory and motor brainstem nuclei. Brains from adult, male rats were recovered over 1 month after midline fluid percussion or sham injury. The principal trigeminal nucleus (PrV, sensory nucleus) and facial nucleus (VIIN, motor nucleus) were examined for neuropathology (silver histochemistry) and microglial activation (Iba1). Significant neuropathology in PrV was evident at 2 and 7 days post-injury compared to sham. Iba1-labeled microglia showed swollen somata and thickened processes over 1 month post-injury. In contrast, the VIIN showed non-significant neuropathology and reduced labeling of activated Iba1 microglia over 1 month post-injury. Together with our previous data, neuropathology and neuroinflammation in the whisker somatosensory pathway may contribute to post-injury sensory sensitivity more than the motor pathway. Whether these findings are direct results of the mechanical injury or consequences of progressive degeneration remains to be determined.

Experimental Traumatic Brain Injury Induces Chronic Glutamatergic Dysfunction in Amygdala Circuitry Known to Regulate Anxiety-Like Behavior

“…Bar graphs represent mean ± SEM. (Miremami et al, 2014;Morrison et al, 2017;Thomas et al, 2018), and dynamics over time are region-dependent; these data do not provide evidence that microglia have a role in mediating glutamate neurotransmission in BLA-CeA communication at 28 DPI.…”

“…Forty-micron thick sections were taken in the coronal plane and wet-mounted on 2%-gelatin-subbed slides before being stained with ionized calcium binding adaptor molecule (Iba1) primary antibody and 3,3 -Diaminobenzidine (DAB) visualization (NeuroScience Associates, Knoxville, TN, United States) to identify all microglia. Images and analysis of alternate regions of the same histology (for all NSA tissue) has been previously described (Cao et al, 2012;Lifshitz and Lisembee, 2012;Miremami et al, 2014;Rowe et al, 2016;Hoffman et al, 2017;Morrison et al, 2017;Thomas et al, 2018).…”

Does time heal all wounds? Experimental diffuse traumatic brain injury results in persisting histopathology in the thalamus

“…Brains were then shipped to Neuroscience Associates Inc. (Knoxville, TN). Data has been previously published for other brain regions 51,69–71 . For GFAP immunohistochemistry, rats were perfused with 4% paraformaldehyde after a PBS flush, then cryoprotected in graded sucrose solutions (15%, 30%) and frozen in optimal cutting temperature compound (Fisher Scientific, #14-373-65).…”

Traumatic Brain Injury-Induced Sex-Dependent Changes in Late-Onset Sensory Hypersensitivity and Glutamate Neurotransmission

“…Within this circuitry, glutamatergic input from the principal trigeminal nucleus (PrV) projects to the contralateral ventral posteromedial nucleus of the thalamus (VPM) that extends long range glutamatergic projections to the primary somatosensory cortex (S1BF). Midline FPI causes pathological alterations along the whisker circuit that are characterized by changes in glutamate neurotransmission, axotomy, dendritic atrophy, circuit reorganization, and gliosis that parallel the development of late-onset sensory hypersensitivity in male rats after TBI (34)(35)(36)(37)(38), similar to agitation presented in human TBI (39). At 1-week post-injury, rats exposed to FPI did not exhibit sensitivity to whisker stimulation (40), similar to clinical reports in the De Koning study, where symptoms developed over time (14).…”