Nano-PSO Administration Attenuates Cognitive and Neuronal Deficits Resulting from Traumatic Brain Injury.

Traumatic Brain Injury (TBI), is one of the most common causes of neurological damage in young populations. It is widely considered as a risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's (PD) disease. These diseases are characterized in part by the accumulation of disease-specific misfolded proteins and share common pathological features, such as neuronal death, as well as inflammatory and oxidative damage. Nano formulation of Pomegranate seed oil [Nano-PSO (Granagard TM)] has been shown to target its active ingredient to the brain and thereafter inhibit memory decline and neuronal death in mice models of AD and genetic Creutzfeldt Jacob disease. In this study, we show that administration of Nano-PSO to mice before or after TBI application prevents cognitive and behavioral decline. In addition, immuno-histochemical staining of the brain indicates that preventive Nano-PSO treatment significantly decreased neuronal death, reduced gliosis and prevented mitochondrial damage in the affected cells. Finally, we examined levels of Sirtuin1 (SIRT1) and Synaptophysin (SYP) in the cortex using Western blotting. Nano-PSO consumption led to higher levels of SIRT1 and SYP protein postinjury. Taken together, our results indicate that Nano-PSO, as a natural brain-targeted antioxidant, can prevent part of TBI-induced damage.

Sex-specific cognitive effects of mild traumatic brain injury to the frontal and temporal lobes.

BACKGROUND: Cognitive deficits are the most enduring and debilitating sequelae of mild traumatic brain injury (mTBI). However, relatively little is known about whether the cognitive effects of mTBI vary with respect to time post-injury, biological sex, and injury location. OBJECTIVES: The aim of this study was to assess the effect of the side and site of mTBI and to determine whether these effects are sexually dimorphic. METHODS: Male and female ICR mice were subjected to either a sham procedure or mTBI to the temporal lobes (right-sided or left-sided) or to the frontal lobes (bilateral) using a weight-drop model. After recovery, mice underwent a battery of behavioral tests at two post-injury time points. RESULTS: Different mTBI impact locations produced dissociable patterns of memory deficits; the extent of these deficits varied across sexes, time points, and memory domains. In both sexes, frontal mTBI mice exhibited a delayed onset of spatial memory deficits. Additionally, the performance of the frontal and left temporal injured males and females was more variable than that of controls. Interestingly, only in females does the effect of mTBI on visual recognition memory depend on the time post-injury. Moreover, only in females does spatial recognition memory remain relatively intact after mTBI to the left temporal lobe. CONCLUSION: This study showed that different mTBI impact sites produce dissociable and sex-specific patterns of cognitive deficits in mice. The results emphasize the importance of considering the injury site/side and biological sex when evaluating the cognitive sequelae of mTBI.

No Significant Effects of Cellphone Electromagnetic Radiation on Mice Memory or Anxiety: Some Mixed Effects on Traumatic Brain Injured Mice.

Current literature details an array of contradictory results regarding the effect of radiofrequency electromagnetic radiation (RF-EMR) on health, both in humans and in animal models. The present study was designed to ascertain the conflicting data published regarding the possible impact of cellular exposure (radiation) on male and female mice as far as spatial memory, anxiety, and general well-being is concerned. To increase the likelihood of identifying possible "subtle" effects, we chose to test it in already cognitively impaired (following mild traumatic brain injury; mTBI) mice. Exposure to cellular radiation by itself had no significant impact on anxiety levels or spatial/visual memory in mice. When examining the dual impact of mTBI and cellular radiation on anxiety, no differences were found in the anxiety-like behavior as seen at the elevated plus maze (EPM). When exposed to both mTBI and cellular radiation, our results show improvement of visual memory impairment in both female and male mice, but worsening of the spatial memory of female mice. These results do not allow for a decisive conclusion regarding the possible hazards of cellular radiation on brain function in mice, and the mTBI did not facilitate identification of subtle effects by augmenting them.

Orally Administered Cinnamon Extract Attenuates Cognitive and Neuronal Deficits Following Traumatic Brain Injury.

The present paper shows how cinnamon extract (CE) consumption mitigates neuronal loss and memory impairment following traumatic brain injury (TBI), one of the world's most common neurodegenerative diseases. TBI patients suffer short- and long-term behavioral, cognitive, and emotional impairments, including difficulties in concentration, memory loss, and depression. Research shows that CE application can mitigate cognitive and behavioral impairments in animal models for Alzheimer's and Parkinson's disease, whose pathophysiology is similar to that of TBI. This study builds on prior research by showing similar results in TBI mice models. After drinking CE for a week, mice were injured using our 70-g weight drop TBI device. For 2 weeks thereafter, the mice continued drinking CE alongside standard lab nutrition. Subsequently, the mice underwent behavioral tests to assess their memory, motor activity, and anxiety. The mice brains were harvested for immunohistochemistry staining to evaluate overall neuronal survival. Our results show that CE consumption almost completely mitigates memory impairment and decreases neuronal loss after TBI. Mice that did not consume CE demonstrated impaired memory. Our results also show that CE consumption attenuated neuronal loss in the temporal cortex and the dentate gyrus. Mice that did not consume CE suffered a significant neuronal loss. There were no significant differences in anxiety levels and motor activity between all groups. These findings show a new therapeutic approach to improve cognitive function and decrease memory loss after TBI.

Repetitive Mild Traumatic Brain Injury and Transcription Factor Modulation.

The worldwide incidence of traumatic brain injury (TBI) is ∼0.5% per year and the frequency is significantly higher among military personnel and athletes. Repetitive TBIs are associated with military and athletic activities, and typically involve more severe consequences. The majority of TBIs are mild; however, these still can result in long-term cognitive deficits, and there is currently no effective treatment. tert-Butylhydroquinone (tBHQ) and pioglitazone can activate the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and peroxisome proliferator-activated receptor-gamma (PPAR-γ) transcription factors, respectively, and each has been shown to be neuroprotective in various model systems. We examined behavioral and gene expression changes after repetitive mild TBI followed by simultaneous treatment with both factors. We used a repetitive closed head injury of mice involving five injuries with a 1-week interval between each TBI. We found that memory performance was significantly reduced by the injuries, unless the TBIs were followed by the tBHQ and pioglitazone administrations. Certain genes; for example, growth hormone and osteopontin, were downregulated by the injury, and this was reversed by the treatment, whereas other genes; for example, a tumor necrosis factor receptor, were upregulated by the injury and restored if the post-injury treatment was administered. Analysis of gene expression levels affected by the injury and/or the treatment point to potential mechanisms that could be exploited therapeutically.

The Invisibility of Mild Traumatic Brain Injury: Impaired Cognitive Performance as a Silent Symptom.

The present study was designed to tackle two notorious features of mild traumatic brain injury (mTBI)-heterogeneity and invisibility-by characterizing the full scope of mTBI symptoms. Mice were exposed to brain injuries of different intensities utilizing a weight-drop model (10, 30, 50, and 70 g) and subsequently subjected to a comprehensive battery of behavioral tests at different time points and immunohistochemical examination of cortical slices. Whereas the physiological, neurological, emotional, and motor function of mTBI mice (i.e., their well-being) remained largely intact, cognitive deficits were identified by the y-maze and novel object recognition. Results from these two cognitive tests were combined and a dose-response relationship was established between injury intensity and cognitive impairment, ranging from an 85% decline after a 70-g impact (p < 0.001) to a 20% decline after a 10-g impact (essentially no effect). In addition, higher intensities of injury were accompanied by decreased expression of axonal and synaptic markers. Thus, our mTBI mice showed a clear discrepancy between performance (poor cognitive function) and appearance (healthy demeanor). This is of major concern given that diagnosis of mTBI is established on the presence of clinical symptoms and emphasizes the need for an alternative diagnostic modality.