Journal of neurotrauma
-
Journal of neurotrauma · Jan 2018
ReviewThe Impact of Traumatic Brain Injury on Later Life: Effects on Normal Aging and Neurodegenerative Diseases.
The acute and chronic effects of traumatic brain injury (TBI) have been widely described; however, there is limited knowledge on how a TBI sustained during early adulthood or mid-adulthood will influence aging. Epidemiological studies have explored whether TBI poses a risk for dementia and other neurodegenerative diseases associated with aging. ⋯ The data support the suggestion that pathological changes triggered by an earlier TBI will have an influence on normal aging processes and will interact with neurodegenerative disease processes rather than the development of a specific disease, such as Alzheimer's or Parkinson's. Chronic neurophysiologic change after TBI may have detrimental effects on neurodegenerative disease.
-
Journal of neurotrauma · Jan 2018
Traumatic brain injury in hTau model mice: Enhanced acute macrophage response and altered long-term recovery.
Traumatic brain injury (TBI) induces widespread neuroinflammation and accumulation of microtubule associated protein tau (MAPT): two key pathological features of tauopathies. This study sought to characterize the microglial/macrophage response to TBI in genomic-based MAPT transgenic mice in a Mapt knockout background (called hTau). Two-month-old hTau and age-matched control male and female mice received a single lateral fluid percussion TBI or sham injury. ⋯ A battery of behavioral tests revealed that TBI in hTau mice resulted in compromised use of spatial search strategies to complete a water maze task, despite lack of motor or visual deficits. Collectively, these data indicate that the presence of wild-type human tau alters the microglial/macrophage response to a single TBI, induces delayed, region-specific MAPT pathology, and alters cognitive recovery; however, the causal relationship between these events remains unclear. These results highlight the potential significance of communication between MAPT and microglia/macrophages following TBI, and emphasize the role of neuroinflammation in post-injury recovery.
-
Journal of neurotrauma · Jan 2018
ABCG2 c.421C>A is Associated with Outcomes Following Severe Traumatic Brain Injury.
Traumatic brain injury (TBI) is a leading cause of death with no pharmacological treatments that improve outcomes. Transporter proteins participate in TBI recovery by maintaining the central nervous system (CNS) biochemical milieu. Genetic variations in transporters that alter expression and/or function have been associated with TBI outcomes. ⋯ Overall, variant alleles at ABCG2 c.421C>A associate with better GOS scores post-injury in two independently sampled cohorts. This finding is mitigated by increasing subject age. This suggests that ABCG2 might have an age-dependent effect on TBI recovery and should be explored in future mechanistic studies.
-
Journal of neurotrauma · Jan 2018
Increased binding potential of brain adenosine A1 receptor in chronic stages of patients with diffuse axonal injury measured with [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine PET imaging.
The positron emission tomography (PET) radioligand for adenosine A1 receptor (A1R) [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX) has recently been developed for human brain imaging. In the present study, we evaluated the alteration of the A1R in patients with diffuse axonal injury (DAI) in chronic stage in vivo. Ten patients with DAI (7 men and 3 women) were included in this study. ⋯ The area with significantly increased 11C-MPDX binding, lower frontal cortex, rolandic area, and posterior cingulate gyrus, did not overlap with the areas of neuronal loss detected by decreased 11C-FMZ binding and did not completely overlap with area of reduced18F-FDG uptake. We obtained the first 11C-MPDX PET images reflecting the A1R BPND in human DAI brain in vivo. 11C-MPDX depicted increased A1R BPND in the areas surrounding the injured brain, whereas 18F-FDG demonstrated reduction throughout the brain. The results suggested that A1R might continuously confer neuroprotective or neuromodulatory effects in DAI even in the chronic stage.
-
Journal of neurotrauma · Jan 2018
Protection against TBI-induced neuronal death with post-treatment with a selective calpain-2 inhibitor in mice.
Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide. The calcium-dependent protease, calpain, has been shown to be involved in TBI-induced neuronal death. However, whereas various calpain inhibitors have been tested in several animal models of TBI, there has not been any clinical trial testing the efficacy of calpain inhibitors in human TBI. ⋯ Calpain-1 KO enhanced cell death, whereas calpain-2 activity correlated with the extent of cell death, suggesting that calpain-1 activation suppresses and calpain-2 activation promotes cell death following TBI. Systemic injection(s) of a calpain-2 selective inhibitor, NA101, at 1 h or 4 h after CCI significantly reduced calpain-2 activity and cell death around the impact site, reduced the lesion volume, and promoted motor and learning function recovery after TBI. Our data indicate that calpain-1 activity is neuroprotective and calpain-2 activity is neurodegenerative after TBI, and that a selective calpain-2 inhibitor can reduce TBI-induced cell death.