Progressive Histopathological Damage Occurring Up to One Year after Experimental Traumatic Brain Injury Is Associated with Cognitive Decline and Depression-Like Behavior

Abstract

Increasing clinical and experimental evidence suggests that traumatic brain injury (TBI) is associated with progressive histopathological damage. The aim of the current study was to characterize the time course of motor function, memory performance, and depression-like behavior up to 1 year after experimental TBI, and to correlate these changes to histopathological outcome. Male C57BL/6N mice underwent controlled cortical impact (CCI) or sham operation, and histopathological outcome was evaluated 15 min, 24 h, 1 week, or 1, 3, 6, or 12 months thereafter (n = 12 animals per time point). Motor function, depression-like behavior, and memory function were evaluated concomitantly, and magnetic resonance imaging (MRI) was repeatedly performed. Naïve mice (n = 12) served as an unhandled control group. Injury volume almost doubled within 1 year after CCI ( p = 0.008) and the ipsilateral hemisphere became increasingly atrophic ( p < 0.0001). Progressive tissue loss was observed in the corpus callosum ( p = 0.007) and the hippocampus ( p = 0.004) together with hydrocephalus formation ( p < 0.0001). Motor function recovered partially after TBI, but 6 months after injury progressive depression-like behavior ( p < 0.0001) and loss of memory function ( p < 0.0001) were observed. The present study demonstrates that delayed histopathological damage that occurs over months after brain injury is followed by progressive depression and memory loss, changes also observed after TBI in humans. Hence, experimental TBI models in mice replicate long-term sequelae of brain injury such as post-traumatic dementia and depression.

Influence of Organic Solvents on Secondary Brain Damage after Experimental Traumatic Brain Injury

“…Of note, the present study assessed an early time-point after TBI that is very commonly used in experimental TBI studies. As it is becoming more and more obvious that TBIinduced brain damage evolves over much longer periods than previously thought (Mao et al 61 ), potential long-term effects of NMP will have to be evaluated. Hence, additional studies need to be performed to further characterize its effects on long-term lesion progression and its mechanisms of action.…”

Chronic traumatic encephalopathy—a blueprint for the bridge between neurological and psychiatric disorders

“…For example, many reports describe an increase in depressive-like behavior in models of TBI, in good accordance with the clinical studies. The most convincing hallmark of those reports is the concurrence of the depressive-like phenotype, which is recognized despite the fact that these studies are being handled in different institutes using a wide range of parameters, such as age, animal species, injury models, severity of injury and time post-injury 100,101,[114][115][116][117][118][119] . Therefore, these findings suggest that depression is a robust consequence of TBI.…”

New Mechanistic Insights, Novel Treatment Paradigms, and Clinical Progress in Cerebrovascular Diseases

“…NP (Munich, Germany) showed that controlled cortical impact in adult mice induces progressive cognitive decline (Mao et al, 2020). While motor function recovered partially after TBI, depression-like behavior and the loss of memory function were progressive.…”