Glial Activation in the Thalamus Contributes to Vestibulomotor Deficits Following Blast-Induced Neurotrauma

Abstract

Vestibular impairment has become a frequent consequence following blast-related traumatic brain injury (bTBI) in military personnel and Veterans. Behavioral outcomes such as depression, fear and anxiety are also common comorbidities of bTBI. To accelerate pre-clinical research and therapy developments, there is a need to study the link between behavioral patterns and neuropathology. The transmission of neurosensory information often involves a pathway from the cerebral cortex to the thalamus, and the thalamus serves crucial integrative functions within vestibular processing. Pathways from the thalamus also connect with the amygdala, suggesting thalamic and amygdalar contributions to anxiolytic behavior. Here we used behavioral assays and immunohistochemistry to determine the sub-acute and early chronic effects of repeated blast exposure on the thalamic and amygdala nuclei. Behavioral results indicated vestibulomotor deficits at 1 and 3 weeks following repeated blast events. Anxiety-like behavior assessments depicted trending increases in the blast group. Astrogliosis and microglia activation were observed upon post-mortem pathological examination in the thalamic region, along with a limited glia response in the amygdala at 4 weeks. These findings are consistent with a diffuse glia response associated with bTBI and support the premise that dysfunction within the thalamic nuclei following repeated blast exposures contribute to vestibulomotor impairment.

Chronic Anxiety- and Depression-Like Behaviors Are Associated With Glial-Driven Pathology Following Repeated Blast Induced Neurotrauma

“…Blast injuries were performed as described in Dickerson et al (2020). Briefly, the blast wave was generated using a custom Advanced Blast Simulator (ABS; 200 cm × 30.48 cm × 30.48 cm) located at the Center for Injury Biomechanics at Virginia Tech University.…”

Secondary thalamic neuroinflammation after focal cortical stroke and traumatic injury mirrors corticothalamic functional connectivity

“…There is mounting evidence that the thalamus, a remote subcortical region, may contribute to postinjury deficits (Cao et al., 2020; Dickerson et al., 2020; Grossman & Inglese, 2016; Grossman et al., 2012; Kuchcinski et al., 2017; Lutkenhoff et al., 2020; Sandsmark et al., 2017; Scott et al., 2015). Despite being insulated from the primary site of cortical injury, the ipsilateral thalamus exhibits intensifying secondary neuroinflammation even while the cortical inflammatory response associated with the primary injury abates.…”

Blast-Induced Neurotrauma Results in Spatially Distinct Gray Matter Alteration Alongside Hormonal Alteration: A Preliminary Investigation

“…The thalamus has a key role for integrating sensory and motor information and may be an underappreciated site of brain injury [ 78 ]. Volumetric alterations of the thalamus have been demonstrated in moderate–severe TBI [ 79 ], with the thalamus also recently highlighted as an important site of pathology in preclinical BINT models [ 28 , 80 ]. Due to these findings, we performed exploratory volumetric analyses of the thalamic nuclei and found significant reductions in the anteroventral nucleus, lateral and medial geniculate nuclei, and pulvinar nucleus.…”