Influence of Age on Brain Edema Formation, Secondary Brain Damage and Inflammatory Response after Brain Trauma in Mice

Abstract

After traumatic brain injury (TBI) elderly patients suffer from higher mortality rate and worse functional outcome compared to young patients. However, experimental TBI research is primarily performed in young animals. Aim of the present study was to clarify whether age affects functional outcome, neuroinflammation and secondary brain damage after brain trauma in mice. Young (2 months) and old (21 months) male C57Bl6N mice were anesthetized and subjected to a controlled cortical impact injury (CCI) on the right parietal cortex. Animals of both ages were randomly assigned to 15 min, 24 h, and 72 h survival. At the end of the observation periods, contusion volume, brain water content, neurologic function, cerebral and systemic inflammation (CD3+ T cell migration, inflammatory cytokine expression in brain and lung, blood differential cell count) were determined. Old animals showed worse neurological function 72 h after CCI and a high mortality rate (19.2%) compared to young (0%). This did not correlate with histopathological damage, as contusion volumes were equal in both age groups. Although a more pronounced brain edema formation was detected in old mice 24 hours after TBI, lack of correlation between brain water content and neurological deficit indicated that brain edema formation is not solely responsible for age-dependent differences in neurological outcome. Brains of old naïve mice were about 8% smaller compared to young naïve brains, suggesting age-related brain atrophy with possible decline in plasticity. Onset of cerebral inflammation started earlier and primarily ipsilateral to damage in old mice, whereas in young mice inflammation was delayed and present in both hemispheres with a characteristic T cell migration pattern. Pulmonary interleukin 1β expression was up-regulated after cerebral injury only in young, not aged mice. The results therefore indicate that old animals are prone to functional deficits and strong ipsilateral cerebral inflammation without major differences in morphological brain damage compared to young.

Effect of Aging on Brain Injury Prediction in Rotational Head Trauma—A Parameter Study with a Rat Finite Element Model

“…The brain tissue properties used in the young adult, mature adult, and old age FE models are listed in Table D1 (see online supplement). Timaru-Kast et al (2012) found an 8% brain volume reduction when brain atrophy was measured through imaging in young (2 months) and old age mice (21 months). Based on these results, the brain volume (including all soft tissue regions and the ventricles) of the old age brain FE model was established by scaling the young adult brain model geometry with a factor of 0.97 in the x, y, and z directions with respect to the brain center of gravity.…”

Age-Dependent Alterations in the Interactions of NF-κB and N-myc with GLT-1/EAAT2 Promoter in the Pericontusional Cortex of Mice Subjected to Traumatic Brain Injury

“…In addition, it has been reported to regulate expression of various cytokines, cell adhesion molecules, oxidative-stress related enzymes, cell surface receptors, and acute-phase proteins associated genes. Glutamate homeostasis is abnormally affected by TBI which in turn leads to prolonged neuronal depolarization, ionic imbalance, enhanced calcium influx, and ATP depletion [28]. Literatures also indicate that NF-κB play a key role in stimulation of the glial cell proliferation, cerebral edema, and inflammation by upregulating the expression of glial fibrillary acidic protein (GFAP) [29], aquaporin-4 (AQP4) [30], and TNF-α [14], which have been used as markers of TBI-induced astrocyte proliferation, inflammation and cerebral edema, respectively.…”

Osthole Enhances the Therapeutic Efficiency of Stem Cell Transplantation in Neuroendoscopy Caused Traumatic Brain Injury

“…68) Interestingly, in the secondary injury process these pro-inflammatory cytokines always overexpress and play a deleterious role in damaging tissue. 69) In this study we mainly focused on the outcome of anti-inflammation changed by the three secondary injury therapeutic methods. It is noteworthy that osthole did not affect the number of GFAP in the similar model as our previous studies (the diameter of the needle is 1.1 mm and the speed of the insertion is faster than 100 µm/s), which may be related to the size of the wound area and the degree of trauma.…”