Behavioral deficits after mild traumatic brain injury by fluid percussion in rats.

Mild traumatic brain injury (TBI) can lead to various disorders, encompassing cognitive and psychiatric complications. While pre-clinical studies have long investigated behavioral alterations, the fluid percussion injury (FPI) model still lacks a comprehensive behavioral battery that includes psychiatric-like disorders. To address this gap, we conducted multiple behavioral tasks over two months in adult male Wistar rats, focusing on mild FPI. Statistical analyses revealed that both naive and sham animals exhibited an increase in sweet liquid consumption over time. In contrast, the TBI group did not show any temporal changes, although mild FPI did induce a statistically significant decrease in sucrose consumption compared to control groups during the chronic phase. Additionally, social interaction tasks indicated reduced contact time in TBI animals. The elevated plus maze task demonstrated an increase in open-arm exploration following fluid percussion. Nonetheless, no significant differences were observed in the acute and chronic phases for the forced swim and light-dark box tasks. Evaluation of three distinct memory tasks in the chronic phase revealed that mild FPI led to long-term memory deficits, as assessed by the object recognition task, while the surgical procedure itself resulted in short-term spatial memory deficits, as evaluated by the Y-maze task. Conversely, working memory remained unaffected in the water maze task. Collectively, these findings provide a nuanced characterization of behavioral deficits induced by mild FPI.

Development and Application of a Novel Pressure System for Evaluating Trauma Severities Using a Physiological Approach After Traumatic Brain Injury in Rats.

OBJECTIVE: The fluid percussion injury (FPI) model is a surgical method for mimicking traumatic brain injury (TBI) models as it automatically and accurately measures peak impact pressure. Nevertheless, its elevated costs have led numerous researchers to develop more inexpensive alternative methods. Therefore, we used a copy of the classic FPI device to develop a novel method to evaluate the pressure pulse and determine injury severity with even more precision during the surgical procedure to induce an injury. METHODS: The electronic components, algorithms, and hardware assembly were initially studied. Adult male Wistar rats received 2 different impact forces, and our novel system measured the pressure pulse in atmospheres to verify the differences between mild and moderate severity and the physiological alterations. RESULTS: The newly developed system was capable of detecting differences between mild and moderate severity, and severity parameters (e.g., apnea and unconsciousness) were more significant in animals with more moderate FPI than those with mild FPI. Additionally, electrocardiographic signals were modified 1 day after TBI, and mild and moderate FPI decreased R-wave peak to R-wave peak intervals (increased heart rate) and high frequency (HF) index as well as increased low frequency (LF) and low frequency/high frequency ratio indices. All electrocardiographic parameters evaluated were more expressive in the more moderate FPI than in the mild one, corroborating clinical heart impairments after TBI. CONCLUSIONS: The method developed to evaluate pressure pulse in an FPI model proved capable of precisely determining different degrees of injury.

The immunological influence of physical exercise on TBI-induced pathophysiology: Crosstalk between the spleen, gut, and brain.

Traumatic brain injury (TBI) is a non-degenerative and non-congenital insult to the brain and is recognized as a global public health problem, with a high incidence of neurological disorders. Despite the causal relationship not being entirely known, it has been suggested that multiorgan inflammatory response involving the autonomic nervous system and the spleen-gut brain axis dysfunction exacerbate the TBI pathogenesis in the brain. Thus, applying new therapeutic tools, such as physical exercise, have been described in the literature to act on the immune modulation induced by brain injuries. However, there are caveats to consider when interpreting the effects of physical exercise on this neurological injury. Given the above, this review will highlight the main findings of the literature involving peripheral immune responses in TBI-induced neurological damage and how changes in the cellular metabolism of the spleen-gut brain axis elicited by different protocols of physical exercise alter the pathophysiology induced by this neurological injury.

The Impact of High-Intensity Interval Training on Brain Derived Neurotrophic Factor in Brain: A Mini-Review.

The brain-derived neurotrophic factor (BDNF) is a protein mainly synthetized in the neurons. Early evidence showed that BDNF participates in cognitive processes as measured at the hippocampus. This neurotrophin is as a reliable marker of brain function; moreover, recent studies have demonstrated that BDNF participates in physiological processes such as glucose homeostasis and lipid metabolism. The BDNF has been also studied using the exercise paradigm to determine its response to different exercise modalities; therefore, BDNF is considered a new member of the exercise-related molecules. The high-intensity interval training (HIIT) is an exercise protocol characterized by low work volume performed at a high intensity [i.e., ≥80% of maximal heart rate (HRmax)]. Recent evidence supports the contention that HIIT elicits higher fat oxidation in skeletal muscle than other forms of exercise. Similarly, HIIT is a good stimulus to increase maximal oxygen uptake (VO2max). Few studies have investigated the impact of HIIT on the BDNF response. The present work summarizes the effects of acute and long-term HIIT on BDNF.

Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise.

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.

Regulation of Mitochondrial Function and Glutamatergic System Are the Target of Guanosine Effect in Traumatic Brain Injury.

Traumatic brain injury (TBI) is a highly complex multi-factorial disorder. Experimental trauma involves primary and secondary injury cascades that underlie delayed neuronal dysfunction and death. Mitochondrial dysfunction and glutamatergic excitotoxicity are the hallmark mechanisms of damage. Accordingly, a successful pharmacological intervention requires a multi-faceted approach. Guanosine (GUO) is known for its neuromodulator effects in various models of brain pathology, specifically those that involve the glutamatergic system. The aim of the study was to investigate the GUO effects against mitochondrial damage in hippocampus and cortex of rats subjected to TBI, as well as the relationship of this effect with the glutamatergic system. Adult male Wistar rats were subjected to a unilateral moderate fluid percussion brain injury (FPI) and treated 15 min later with GUO (7.5 mg/kg) or vehicle (saline 0.9%). Analyses were performed in hippocampus and cortex 3 h post-trauma and revealed significant mitochondrial dysfunction, characterized by a disrupted membrane potential, unbalanced redox system, decreased mitochondrial viability, and complex I inhibition. Further, disruption of Ca2+ homeostasis and increased mitochondrial swelling was also noted. Our results showed that mitochondrial dysfunction contributed to decreased glutamate uptake and levels of glial glutamate transporters (glutamate transporter 1 and glutamate aspartate transporter), which leads to excitotoxicity. GUO treatment ameliorated mitochondrial damage and glutamatergic dyshomeostasis. Thus, GUO might provide a new efficacious strategy for the treatment acute physiological alterations secondary to TBI.

The Effects of Creatine Supplementation and Physical Exercise on Traumatic Brain Injury.

Traumatic brain injury (TBI) is a devastating disease frequently followed by significant behavioral disabilities and long-term medical complications that include a wide range of behavioral and emotional problems. TBI is characterized by a combination of immediate mechanical dysfunction of brain tissue and secondary damage developed over a longer period of time following the injury. The early inflammatory response after tissue injury can be triggered by several factors such as extravasated blood products and reactive oxygen species (ROS). It is important to note that energy generation and mitochondrial function are closely related to and interconnected with delayed secondary manifestations of brain injury, including early neuromotor dysfunction, cognitive impairment and post-traumatic epilepsy (PTE). Given the extent of post-traumatic changes in neuronal function and the possibility of amplifying secondary cascades, different therapies designed to minimize damage and retain/restore cellular function after TBI are currently being studied. In this context, the present review covers the preclinical and clinical literature investigating the role of inflammation and free radicals in secondary damage generated by several models of TBI. Furthermore, the present review aims to discuss the role of creatine, a guanidine compound popularly used as a performance-enhancing supplement for high-intensity athletic performance, in secondary damage induced by TBI. In this narrative review, we also discuss the beneficial effect of exercise performed in animal models of TBI and how the results from animal studies can be applied to clinical settings.