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

Abstract

These data indicate that dTBI results in persisting thalamic histopathology out to a chronic time point. While these changes can be indicative of either adaptive (recovery) or maladaptive (neurological dysfunction) circuit reorganization, they also provide a potential mechanism by which maladaptive circuit reorganization could contribute to the development of chronic neurological dysfunction. Understanding the processes that mediate circuit reorganization is critical to the development of future therapies for TBI patients.

Neurochemical regulation of the expression and function of glial fibrillary acidic protein in astrocytes

“…TBI is a significant risk factor for the development of neurodegenerative disorders such as chronic traumatic encephalopathy, posttraumatic epilepsy and Alzheimer disease and PD diseases. In addition to tau pathologies, caspase-3-mediated apoptosis, neuroinflammation and microvascular alteration (Glushakova et al, 2018), chronic TBI significantly increases astrocyte activation as manifested in GFAP expression (Thomas et al, 2018). In GFAP-null mice, the brain is highly susceptible to cerebral ischemia (Nawashiro, Brenner, Fukui, Shima, & Hallenbeck, 2000) and the downregulation of IF proteins by siRNA is likely an effective treatment for spinal cord injury (Toyooka, Nawashiro, Shinomiya, & Shima, 2011).…”

Computation of history-dependent mechanical damage of axonal fiber tracts in the brain: towards tracking sub-concussive and occupational damage to the brain

“…However, note that B and 7 recover to zero, while 48Ö and 459 recover to 1. Many researchers have studied the recovery process that follows TBI [39] [40] [41] [42] [43]. However, a definitive relationship between recovery time and impact severity, location, and frequency has not yet been established.…”

“…For example, in the case of minor sports injuries, symptoms tend to subside in seven to ten days [44]. However, for more severe injuries, many TBI patients go on to develop post-concussive syndrome (PCS), which is associated with long term cognitive deficits and white matter changes [45] [46] [43]. Due to the lack of a generalized recovery criteria, we have assumed a simple exponential healing model that provides a full recovery after six months (i.e., = 0.025), which is based on a three to six month recovery time for the typical civilian mTBI [45].…”

Diffuse TBI-induced expression of anxiety-like behavior coincides with altered glutamatergic function, TrkB protein levels and region-dependent pathophysiology in amygdala circuitry

“…No significant alterations were detected in the BLA in anesthetized rats in this study, although studies using focal TBI models indicate that BLA circuitry becomes weakened through altered neuronal excitability, changes in N-methyl-D-aspartate (NMDA) receptors, and changes to GABAergic production proteins (GAD-67), all of which may provide compensatory responses that primarily influence glutamate release in the CeA 20,64,65 . Previously, we reported increased neuropathology in the somatosensory cortex and thalamus following dTBI, which could also alter sensory input into the BLA 66,67 . Assessment of glutamate neurotransmission in both the BLA and CeA of awake-behaving rats is needed to evaluate simultaneous glutamate signaling in direct response to anxiety-inducing tasks.…”

“…The same image was analyzed three times. The standard deviation between the percent area black was below 10% within each rat.Alternating sections of brains prepared by Neuroscience Associates Inc (Knoxville, TN) (see Iba1 staining methods)44 were cryosectioned, mounted, stained using de Olmos aminocupric silver technique, counterstained with Neutral Red, and cover-slipped. Densitometric quantitative analysis was performed identical to GFAP analysis.…”