In recent years, a paradigm shift in the bidirectional interactions within the gut-brain axis in normal and pathologic conditions has been evidenced. Although the causal relationship is not ...completely known, the application of new therapeutic tools such as physical exercise has been described in several studies. However, there are caveats to consider when interpreting the effect of exercise training on the axis. Therefore, an integrative perspective of the gut and the brain's communication pathway is discussed and the role of exercise on influencing this communication highway is explained in this review.
Display omitted
•The exercise-induced microbiome modulation increases lean mass increase and reduces fat mass.•Moderate physical exercise positively modulates the relationship between the gut and brain.•The stress exercise-induced neurotransmitters chances alter motility and gut permeability.
•Brain pathology impacts the body via autonomic nervous system, endocrine and immune pathways.•Peripheral metabolic dysfunction after TBI exacerbates brain pathology.•Metabolic dysfunction increases ...incidence of long-term neurological disorders after TBI.•Metabolic dysfunction is a predictor of poor outcome in TBI patients.
Traumatic brain injury (TBI) is a devastating condition which often initiates a sequel of neurological disorders that can last throughout lifespan. From metabolic perspective, TBI also compromises systemic physiology including the function of body organs with subsequent malfunctions in metabolism. The emerging panorama is that the effects of TBI on the periphery strike back on the brain and exacerbate the overall TBI pathogenesis. An increasing number of clinical reports are alarming to show that metabolic dysfunction is associated with incidence of long-term neurological and psychiatric disorders. The autonomic nervous system, associated hypothalamic-pituitary axis, and the immune system are at the center of the interface between brain and body and are central to the regulation of overall homeostasis and disease. We review the strong association between mechanisms that regulate cell metabolism and inflammation which has important clinical implications for the communication between body and brain. We also discuss the integrative actions of lifestyle interventions such as diet and exercise on promoting brain and body health and cognition after TBI.
•Traumatic brain injury (TBI) causes systemic inflammation and compromises the function of organs that regulate body response.•The spleen and gut are affected by TBI, and their response can ...exacerbate the neuroinflammatory damage of the injury.•The immune system seems to be the major connection between the brain, spleen, and gut.•Physical exercise can act as a non-pharmacological tool in post-injury treatment.
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.
High consumption of fructose has paralleled an explosion in metabolic disorders including obesity and type 2 diabetes. Even more problematic, sustained consumption of fructose is perceived as a ...threat for brain function and development of neurological disorders. The action of fructose on peripheral organs is an excellent model to understand how systemic physiology impacts the brain. Given the recognized action of fructose on liver metabolism, here we discuss mechanisms by which fructose can impact the brain by interacting with liver and other organs. The interaction between peripheral and central mechanisms is a suitable target to reduce the pathophysiological consequences of neurological disorders.
•High fructose consumption correlates with rising rates of both metabolic and neurologic disorders.•Indirectly, fructose affects food intake by stimulating release of glucocorticoid hormones.•The hypothalamus plays a crucial role on the control of brain and is highly susceptible to the action of fructose.•Oxidative stress and inflammation play a central role in fructose-induced damage to the brain.•Excess dietary fructose fosters neurological and psychiatric disorders.
Traumatic brain injury (TBI) is considered a public health problem and is often related to motor and cognitive disabilities, besides behavioral and emotional changes that may remain for the rest of ...the subject’s life. Resident astrocytes and microglia are the first cell types to start the inflammatory cascades following TBI. It is widely known that continuous or excessive neuroinflammation may trigger many neuropathologies. Despite the large numbers of TBI cases, there is no effective pharmacological treatment available. This study aimed to investigate the effects of the new hybrid molecule 3-ethoxycarbonyl-2-methyl-4-(2-nitrophenyl)-4,11-dihydro1H-pyrido2,3-b1,5benzodiazepine (JM-20) on TBI outcomes. Male Wistar rats were submitted to a weight drop model of mild TBI and treated with a single dose of JM-20 (8 mg/kg). Twenty-four hours after TBI, JM-20–treated animals showed improvements on locomotor and exploratory activities, and short-term memory deficits induced by TBI improved as well. Brain edema was present in TBI animals and the JM-20 treatment was able to prevent this change. JM-20 was also able to attenuate neuroinflammation cascades by preventing glial cells—microglia and astrocytes—from exacerbated activation, consequently reducing pro-inflammatory cytokine levels (TNF-α and IL-1β). BDNF mRNA level was decreased 24 h after TBI because of neuroinflammation cascades; however, JM-20 restored the levels. JM-20 also increased GDNF and NGF levels. These results support the JM-20 neuroprotective role to treat mild TBI by reducing the initial damage and limiting long-term secondary degeneration after TBI.
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.
Traumatic brain injury (TBI) is a devastating disease frequently followed by behavioral disabilities including post-traumatic epilepsy (PTE). Although reasonable progress in understanding its ...pathophysiology has been made, treatment of PTE is still limited. Several studies have shown the neuroprotective effect of creatine in different models of brain pathology, but its effects on PTE is not elucidated. Thus, we decided to investigate the impact of delayed and chronic creatine supplementation on susceptibility to epileptic seizures evoked by pentylenetetrazol (PTZ) after TBI. Our experimental data revealed that 4 weeks of creatine supplementation (300 mg/kg, p.o.) initiated 1 week after fluid percussion injury (FPI) notably increased the latency to first myoclonic and tonic-clonic seizures, decreased the time spent in tonic-clonic seizure, seizure intensity, epileptiform discharges and spindle oscillations induced by a sub-convulsant dose of PTZ (35 mg/kg, i.p.). Interestingly, this protective effect persists for 1 week even when creatine supplementation is discontinued. The anticonvulsant effect of creatine was associated with its ability to reduce cell loss including the number of parvalbumin positive (PARV+) cells in CA3 region of the hippocampus. Furthermore, creatine supplementation also protected against the reduction of GAD67 levels, GAD activity and specific 3Hflunitrazepam binding in the hippocampus. These findings showed that chronic creatine supplementation may play a neuroprotective role on brain excitability by controlling the GABAergic function after TBI, providing a possible new strategy for the treatment of PTE.
•EEG and behavior seizures after TBI were reduced by delayed creatine supplementation.•Creatine exhibited a sustained effect on seizures after TBI.•Creatine reduced brain excitability post-TBI by restoring the impaired GABAergic function.
Display omitted
•Impairments may differ as a function of time after mild fluid percussion injury.•Depression-like behavior is observed only in chronic phases of damage to the head.•Mild brain injury ...by fluid percussion induces mood and affective disorders in rats.•Different memory types are impaired after mild brain injury.•Mild fluid percussion causes impulsivity-like behavior 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.
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.
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.
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.
The method developed to evaluate pressure pulse in an FPI model proved capable of precisely determining different degrees of injury.
Disruption of the blood–brain barrier and occurrence of coagulopathy after traumatic brain injury (TBI) have important implications for multiple secondary injury processes. Given the extent of ...post-traumatic changes in neuronal function, significant alterations in some targets, such thrombin (a protease that plays a physiological role in maintaining blood coagulation), play an important role in TBI-induced pathophysiology. Despite the magnitude of thrombin in synaptic plasticity being concentration-dependent, the mechanisms underlying TBI have not been fully elucidated. The understanding of this post-injury neurovascular dysregulation is essential to establish scientific-based rehabilitative strategies. One of these strategies may be supporting physical exercise, considering its relevance in reducing damage after a TBI. However, there are caveats to consider when interpreting the effect of physical exercise on neurovascular dysregulation after TBI. To complete this picture, this review will describe how the interactions established between blood-borne factors (such as thrombin) and physical exercise alter the TBI pathophysiology.
PDF
