Exploring the association between serum phosphate levels and mortality in patients hospitalized with infectious diseases: a nationwide study.

Objective: The purpose of this study was to examine associations of serum phosphate levels with mortality, target organ damage and length of hospital stay in adults with infectious diseases hospitalized outside of the intensive care unit. Methods: This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. The main exposure variable was the first serum phosphate levels at admission (up to 1 week). The analysis included multivariable logistic regression models and quantile regression. Results: Of 126,088 patients (49% males, mean age: 69.3 years), 24,809 (19.7%) had decreased phosphate levels, 92,730 (73.5%) normal phosphate levels, and 8,549 (6.8%) elevated phosphate levels on admission. Overall- and in-hospital mortality rates were highest among those with hyperphosphatemia (74.5 and 16.4%, respectively), followed by those with normophosphatemia (57.0 and 6.6%), and lastly the hypophosphatemia group (48.7 and 5.6%); p < 0.001 for all. After adjusting for confounders, the lowest predicted mortality rate was observed in the normophosphatemia group. In the multivariable model, hyperphosphatemia conferred a higher probability of target organ damage (OR [95% CI]: 2.43 [2.06-2.86]), while moderate hypophosphatemia conferred a lower probability (OR [95% CI]: 0.73 [0.65-0.82]), compared to normal phosphate levels and extreme hypophosphatemia showed a non-significant association (OR [95% CI]: 0.87 [0.57-1.28]). The associations were independent of renal failure. In a multivariable model, hyperphosphatemia was associated with a slight increase of 0.33 days in length of stay compared to normal phosphate levels. Conclusion: A J-shaped relation was found between phosphate levels and prognosis in patients hospitalized with infectious diseases, regardless of their renal function.

Establishing a 3-Tesla Magnetic Resonance Imaging Method for Assessing Diffuse Axonal Brain Injury in Rats.

Traumatic brain injury (TBI) significantly contributes to death and disability worldwide. However, treatment options remain limited. Here, we focus on a specific pathology of TBI, diffuse axonal brain injury (DABI), which describes the process of the tearing of nerve fibers in the brain after blunt injury. Most protocols to study DABI do not incorporate a specific model for that type of pathology, limiting their ability to identify mechanisms and comorbidities of DABI. In this study, we developed a magnetic resonance imaging (MRI) protocol for DABI in a rat model using a 3-T clinical scanner. We compared the neuroimaging outcomes with histologic and neurologic assessments. In a sample size of 10 rats in the sham group and 10 rats in the DABI group, we established neurological severity scores before the intervention and at 48 h following DABI induction. After the neurological evaluation after DABI, all rats underwent MRI scans and were subsequently euthanized for histological evaluation. As expected, the neurological assessment showed a high sensitivity for DABI lesions indicated using the ß-APP marker. Surprisingly, however, we found that the MRI method had greater sensitivity in assessing DABI lesions compared to histological methods. Out of the five MRI parameters with pathological changes in the DABI model, we found significant changes compared to sham rats in three parameters, and, as shown using comparative tests with other models, MRI was the most sensitive parameter, being even more sensitive than histology. We anticipate that this DABI protocol will have a significant impact on future TBI and DABI studies, advancing research on treatments specifically targeted towards improving patient quality of life and long-term outcomes.

The Relationship between Post-Traumatic Stress Disorder Due to Brain Injury and Glutamate Intake: A Systematic Review.

There is a growing body of evidence that suggests a connection between traumatic brain injury (TBI) and subsequent post-traumatic stress disorder (PTSD). While the exact mechanism is unknown, we hypothesize that chronic glutamate neurotoxicity may play a role. The consumption of dietary glutamate is a modifiable factor influencing glutamate levels in the blood and, therefore, in the brain. In this systematic review, we explored the relationship between dietary glutamate and the development of post-TBI PTSD. Of the 1748 articles identified, 44 met the inclusion criteria for analysis in this review. We observed that individuals from countries with diets traditionally high in glutamate had greater odds of developing PTSD after TBI (odds ratio = 15.2, 95% confidence interval 11.69 to 19.76, p < 0.01). These findings may support the hypothesis that chronically elevated blood glutamate concentrations caused by high dietary intake invoke neurodegeneration processes that could ultimately result in PTSD. Further studies will clarify whether lowering glutamate via diet would be an effective strategy in preventing or treating post-TBI PTSD.

Ethnicity, Progressive Keratoconus, and Outcomes after Corneal Cross-Linking in Southern Israel.

PURPOSE: To assess clinical outcomes of corneal cross-linking (CXL) intervention in a population diagnosed with progressive keratoconus. METHODS: This single-center retrospective cohort study included consecutive patients who underwent standard CXL or accelerated CXL for progressive keratoconus at a major teaching hospital in southern Israel between January 2015 and December 2019. Patients' medical files were reviewed, and pre-operative and post-operative data regarding demographics and clinical and tomographic characteristics were extracted and analyzed. RESULTS: This study included 166 patients (representing 198 eyes), out of which 98 patients (123 eyes) were ethnically Bedouin, and 68 patients (75 eyes) were ethnically Jewish. Overall, 126 patients (144 eyes) had a follow-up of at least 12 months (16.84 ± 5.76). The mean patient age was 20.62 ± 7.1 years old. There were significant baseline differences between the two ethnic groups in best-corrected visual acuity (BCVA; p < 0.001), uncorrected visual acuity (UCVA; p < 0.001), mean keratometry (p = 0.028), and corneal thickness (p < 0.001). Significant changes in BCVA, UCVA, and pachymetry parameters within each group were found after 12 months. Negative binomial regression analysis showed a maximal keratometry below 55D (RR = 1.247, p < 0.001), and a standard CXL procedure (RR = 1.147, p = 0.041) are significantly related to the stability of KC after 12 months. However, the effect size of the origin of patients is negligible (RR = 1.047, p = 0.47). CONCLUSIONS: In this study, the Bedouin population suffered from more progressive keratoconus when compared to the Jewish population. CXL was significantly effective in improving BCVA and UCVA in both groups after 12 months of follow-up. The effect size of the origin of patients on the stability of KC was found to be negligible.

Diet's Impact on Post-Traumatic Brain Injury Depression: Exploring Neurodegeneration, Chronic Blood-Brain Barrier Destruction, and Glutamate Neurotoxicity Mechanisms.

Traumatic brain injury (TBI) has a profound impact on cognitive and mental functioning, leading to lifelong impairment and significantly diminishing the quality of life for affected individuals. A healthy blood-brain barrier (BBB) plays a crucial role in guarding the brain against elevated levels of blood glutamate, making its permeability a vital aspect of glutamate regulation within the brain. Studies have shown the efficacy of reducing excess glutamate in the brain as a treatment for post-TBI depression, anxiety, and aggression. The purpose of this article is to evaluate the involvement of dietary glutamate in the development of depression after TBI. We performed a literature search to examine the effects of diets abundant in glutamate, which are common in Asian populations, when compared to diets low in glutamate, which are prevalent in Europe and America. We specifically explored these effects in the context of chronic BBB damage after TBI, which may initiate neurodegeneration and subsequently have an impact on depression through the mechanism of chronic glutamate neurotoxicity. A glutamate-rich diet leads to increased blood glutamate levels when contrasted with a glutamate-poor diet. Within the context of chronic BBB disruption, elevated blood glutamate levels translate to heightened brain glutamate concentrations, thereby intensifying neurodegeneration due to glutamate neurotoxicity.

Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features. METHODS: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive). RESULTS: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). CONCLUSION: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions.

Challenging the Interpretation of White Blood Cell Counts in Patients with Sepsis Following Packed Cell Transfusion.

Critically ill patients with sepsis often require packed cell transfusions (PCT). However, PCT may affect white blood cell (WBC) counts. We conducted a population-based retrospective cohort study to trace changes in WBC count following PCT in critically ill patients with sepsis. We included 962 patients who received one unit of PCT while hospitalized in a general intensive care unit, and 994 matched patients who did not receive PCT. We calculated the mean values of WBC count for the 24 h before and 24 h after PCT. Multivariable analyses using a mixed linear regression model were performed. The mean WBC count decreased in both groups, but more in the non-PCT group (from 13.9 × 109/L to 12.2 × 109/L versus 13.9 × 109/L to 12.8 × 109/L). A linear regression model showed a mean decrease of 0.45 × 109/L in WBC count over the 24 h following the start of PCT. Every 1.0 × 109/L increase in the WBC count prior to PCT administration showed a corresponding decrease of 0.19 × 109/L in the final WBC count. In conclusion, among critically ill patients with sepsis, PCT causes only mild and clinically non-prominent changes in WBC count.

BODY TEMPERATURE VARIATION AFTER PACKED CELL TRANSFUSION IN ADULT PATIENTS WITH SEPSIS-WHERE WILL THE PENDULUM STOP?

ABSTRACT: Background : Critically ill patients with sepsis often require packed cell transfusions (PCTs). Packed cell transfusion causes changes in body's core temperature. Objective : To trace the course and amplitude of body core temperature after PCT in adults with sepsis. Methods : We conducted a population-based retrospective cohort study of patients with sepsis who received one unit of PCT during their hospitalization in a general intensive care unit during 2000-2019. A control group was established by matching each of these patients to a patient who did not receive PCT. We calculated the mean values of urinary bladder temperature for the 24 h before and 24 h after PCT. To evaluate the effect of PCT on body core temperature, multivariable analyses using a mixed linear regression model were performed. Results : The study comprised 1,100 patients who received one unit of PCT and 1,100 matched patients. The mean temperature before PCT was 37.3°C. Immediately from initiation of PCT, body temperature decreased, to a minimum of 37.0°C. During the 24 subsequent hours, the temperature increased gradually and consistently, until a peak temperature of 37.4°C. In a linear regression model, body core temperature increased by a mean 0.06°C in the first 24 h after PCT and decreased by a mean 0.65°C for every 1.0°C increase before PCT. Conclusions : Among critically ill patients with sepsis, PCT itself causes only mild and clinically insignificant temperature changes. Thus, significant changes in core temperature during the 24 h after PCT may indicate an unusual clinical event that requires clinicians' immediate attention.

The Integrity of the Blood-Brain Barrier as a Critical Factor for Regulating Glutamate Levels in Traumatic Brain Injury.

A healthy blood-brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.

Blood glutamate scavenging as a novel glutamate-based therapeutic approach for post-traumatic brain injury anxiety and social impairment.

Traumatic brain injury (TBI) is a serious condition that is associated with an increased risk of severe, long-term psychiatric consequences. Drugs that target the glutamatergic system have proven successful in treating both TBI and many of its psychiatric sequelae. Blood glutamate scavengers (BGS) cause a decrease in blood glutamate levels, leading to a reduction in glutamate's concentration gradient from the brain to the blood and decreased levels of brain glutamate. This study evaluated the BGS pyruvate as a treatment for TBI-related neuropsychiatric conditions in a rat model. 213 rats were divided into four groups in a 2 × 2 design: Sham or TBI rats treated with pyruvate or control treatment. Magnetic resonance imaging, neurological status, brain glutamate and blood glutamate levels were assessed following the injury. Four weeks after the start of treatment, all rats underwent behavioral tests to assess anxious behavior and social impairment (aggressive and hierarchical behavior). Rats responded positively to pyruvate in several tasks, lowering brain glutamate levels and reducing anxiety and depression, as well as modulating TBI-related changes in social behavior. Glutamate scavenging with pyruvate may be an effective therapeutic option for post-TBI behavioral changes by reducing associated elevations in brain glutamate levels.

Pathophysiology and Current Drug Treatments for Post-Stroke Depression: A Review.

Post-stroke depression (PSD) is a biopsychosocial disorder that affects individuals who have suffered a stroke at any point. PSD has a 20 to 60 percent reported prevalence among stroke survivors. Its effects are usually adverse, can lead to disability, and may increase mortality if not managed or treated early. PSD is linked to several other medical conditions, including anxiety, hyper-locomotor activity, and poor functional recovery. Despite significant awareness of its adverse impacts, understanding the pathogenesis of PSD has proved challenging. The exact pathophysiology of PSD is unknown, yet its complexity has been definitively shown, involving mechanisms such as dysfunction of monoamine, the glutamatergic systems, the gut-brain axis, and neuroinflammation. The current effectiveness of PSD treatment is about 30-40 percent of all cases. In this review, we examined different pathophysiological mechanisms and current pharmacological and non-pharmacological approaches for the treatment of PSD.

Can the Duration of In-Hospital Ventilation in Patients with Sepsis Help Predict Long-Term Survival?

Mechanical ventilation is a cornerstone in the treatment of critical illness, especially sepsis. Prolonged mechanical ventilation, for a duration exceeding 21 days, is associated with higher rates of in-hospital and post-discharge mortality. Our aim was to assess the association between in-hospital ventilation duration and long-term life expectancy in patients ventilated in intensive care units specifically due to sepsis of any origin. We conducted a population-based retrospective cohort study of adults hospitalized in a general intensive care unit for 24 h or more during 2007-2017, who were diagnosed with sepsis or septic shock, treated with invasive mechanical ventilation for a maximum of 60 days and survived hospitalization. The primary exposure was the length of invasive mechanical ventilation. In an adjusted multivariable regression model, survival rates at 1, 2, 3 and 4 years post-hospitalization did not differ significantly between patients who were ventilated for 3-8 days (n = 169), 9-21 days (n = 160) or 22-60 days (n = 170), and those who were ventilated for 1-2 days (n = 192). We concluded that the duration of in-hospital ventilation in patients with sepsis cannot serve as a predictor for long-term survival. Thus, the duration of ventilation in itself should not guide the level of care in ventilated patients with sepsis.

Glutamate Neurotoxicity and Destruction of the Blood-Brain Barrier: Key Pathways for the Development of Neuropsychiatric Consequences of TBI and Their Potential Treatment Strategies.

Traumatic brain injury (TBI) is associated with significant cognitive and psychiatric conditions. Neuropsychiatric symptoms can persist for years following brain injury, causing major disruptions in patients' lives. In this review, we examine the role of glutamate as an aftereffect of TBI that contributes to the development of neuropsychiatric conditions. We hypothesize that TBI causes long-term blood-brain barrier (BBB) dysfunction lasting many years and even decades. We propose that dysfunction in the BBB is the central factor that modulates increased glutamate after TBI and ultimately leads to neurodegenerative processes and subsequent manifestation of neuropsychiatric conditions. Here, we have identified factors that determine the upper and lower levels of glutamate concentration in the brain after TBI. Furthermore, we consider treatments of disruptions to BBB integrity, including repairing the BBB and controlling excess glutamate, as potential therapeutic modalities for the treatment of acute and chronic neuropsychiatric conditions and symptoms. By specifically focusing on the BBB, we hypothesize that restoring BBB integrity will alleviate neurotoxicity and related neurological sequelae.

Retinal and optic nerve magnetic resonance diffusion-weighted imaging in acute non-arteritic central retinal artery occlusion.

OBJECTIVES: Diffusion weighted imaging hyperintensity (DWI-H) has been described in the retina and optic nerve during acute central retinal artery occlusion (CRAO). We aimed to determine whether DWI-H can be accurately identified on standard brain magnetic resonance imaging (MRI) in non-arteritic CRAO patients at two tertiary academic centers. MATERIALS AND METHODS: Retrospective cross-sectional study that included all consecutive adult patients with confirmed acute non-arteritic CRAO and brain MRI performed within 14 days of CRAO. At each center, two neuroradiologists masked to patient clinical data reviewed each MRI for DWI-H in the retina and optic nerve, first independently then together. Statistical analysis for inter-rater reliability and correlation with clinical data was performed. RESULTS: We included 204 patients [mean age 67.9±14.6 years; 47.5% females; median time from CRAO to MRI 1 day (IQR 1-4.3); 1.5 T in 127/204 (62.3%) and 3.0 T in 77/204 (37.7%)]. Inter-rater reliability varied between centers (κ = 0.27 vs. κ = 0.65) and was better for retinal DWI-H. Miss and error rates significantly differed between neuroradiologists at each center. After consensus review, DWI-H was identified in 87/204 (42.6%) patients [miss rate 117/204 (57.4%) and error rate 11/87 (12.6%)]. Significantly more patients without DWI-H had good visual acuity at follow-up (p = 0.038). CONCLUSIONS: In this real-world case series, differences in agreement and interpretation accuracy among neuroradiologists limited the role of DWI-H in diagnosing acute CRAO on standard MRI. DWI-H was identified in 42.6% of patients and was more accurately detected in the retina than in the optic nerve. Further studies are needed with standardized novel MRI protocols.

Potassium Level Variation Following Packed Cell Transfusion in Critically Ill Adult Patients-How Alert Should We Be?

One of the most clinically important effects following the administration of packed cell transfusion (PCT) is hyperkalemia, which can cause severe life-threatening cardiac arrhythmias. This retrospective population-based cohort study included adults hospitalized between January 2007 and December 2019 in a general intensive care unit for 24 h or more, with normal levels of serum potassium on admission. We assessed changes in serum potassium levels after administration of one unit of packed cells and sought to identify clinical parameters that may affect these changes. We applied adjusted linear mixed models to assess changes in serum potassium. The mean increase in serum potassium was 0.09 mEq/L (C.U 0.04−0.14, p-value < 0.001) among the 366 patients who were treated with a single PCT compared to those not treated with PCT. Increased serum potassium levels were also found in patients who required mechanical ventilation, and to a lesser degree in those treated with vasopressors. Hypertension, the occurrence of a cerebrovascular accident, and increased creatinine levels were all associated with reduced serum potassium levels. Due to the small rise in serum potassium levels following PCT, we do not suggest any particular follow-up measures for critically ill patients who receive PCT.

Traumatic brain injury-induced submissive behavior in rats: link to depression and anxiety.

Traumatic brain injury (TBI) affects millions of people worldwide, many of whom are affected with post-TBI mood disorders or behavioral changes, including aggression or social withdrawal. Diminished functionality can persist for decades after TBI and delay rehabilitation and resumption of employment. It has been established that there is a relationship between these mental disorders and brain injury. However, the etiology and causal relationships behind these conditions are poorly understood. Rodent models provide a helpful tool for researching mood disorders and social impairment due to their natural tendencies to form social hierarchies. Here, we present a rat model of mental complications after TBI using a suite of behavioral tests to examine the causal relationships between changes in social behavior, including aggressive, hierarchical, depressive, and anxious behavior. For this purpose, we used multivariate analysis to identify causal relationships between the above post-TBI psychiatric sequelae. We performed statistical analysis using principal component analysis, discriminant analysis, and correlation analysis, and built a model to predict dominant-submissive behavior based on the behavioral tests. This model displayed a predictive accuracy of 93.3% for determining dominant-submissive behavior in experimental groups. Machine learning algorithms determined that in rats, aggression is not a principal prognostic factor for dominant-submissive behavior. Alternatively, dominant-submissive behavior is determined solely by the rats' depressive-anxious state and exploratory activity. We expect the causal approach used in this study will guide future studies into mood conditions and behavioral changes following TBI.

The Development of Novel Drug Treatments for Stroke Patients: A Review.

Acute ischemic stroke is a critical condition that can result in disability and death. The consequences of this medical condition depend on various factors, including the size of the stroke, affected brain region, treatment onset, and the type of treatment. The primary objective of stroke treatment is to restart ischemic penumbra tissue perfusion and reduce infarct volume by sustaining blood flow. Recent research on the condition's pathological pathways and processes has significantly improved treatment options beyond restoring perfusion. Many studies have concentrated on limiting injury severity via the manipulation of molecular mechanisms of ischemia, particularly in animal research. This article reviews completed and ongoing research on the development of acute ischemic stroke drugs. This study focuses on three main categories of antithrombotic drugs, thrombolytic drugs, and neuroprotective agents. The paper outlines findings from animal and clinical trials and explores the working mechanisms of these drugs.

Glutamate Efflux across the Blood-Brain Barrier: New Perspectives on the Relationship between Depression and the Glutamatergic System.

Depression is a significant cause of disability and affects millions worldwide; however, antidepressant therapies often fail or are inadequate. Current medications for treating major depressive disorder can take weeks or months to reach efficacy, have troubling side effects, and are limited in their long-term capabilities. Recent studies have identified a new set of glutamate-based approaches, such as blood glutamate scavengers, which have the potential to provide alternatives to traditional antidepressants. In this review, we hypothesize as to the involvement of the glutamate system in the development of depression. We identify the mechanisms underlying glutamate dysregulation, offering new perspectives on the therapeutic modalities of depression with a focus on its relationship to blood-brain barrier (BBB) permeability. Ultimately, we conclude that in diseases with impaired BBB permeability, such as depression following stroke or traumatic brain injury, or in neurogenerative diseases, the glutamate system should be considered as a pathway to treatment. We propose that drugs such as blood glutamate scavengers should be further studied for treatment of these conditions.

Blood Glutamate Scavenging With Pyruvate as a Novel Preventative and Therapeutic Approach for Depressive-Like Behavior Following Traumatic Brain Injury in a Rat Model.

Depression is a common and serious complication following traumatic brain injury (TBI). Both depression and TBI have independently been associated with pathologically elevated extracellular brain glutamate levels. In the setting of TBI, blood glutamate scavenging with pyruvate has been widely shown as an effective method to provide neuroprotection by reducing blood glutamate and subsequent brain glutamate levels. Here we evaluate pyruvate as a novel approach in the treatment and prevention of post-TBI depression-like behavior in a rat model. Rats were divided into five groups: (1) sham-operated control with pyruvate, (2) sham-operated control with placebo, (3) post-TBI with placebo, (4) post-TBI given preventative pyruvate, and (5) post-TBI treated with pyruvate. These groups had an equal number of females and males. Rats were assessed for depressive-like behavior, neurological status, and glutamate levels in the blood and brain. Post-TBI neurological deficits with concurrent elevations in glutamate levels were demonstrated, with peak glutamate levels 24 h after TBI. Following TBI, the administration of either prophylactic or therapeutic pyruvate led to reduced glutamate levels, improved neurologic recovery, and improved depressive-like behavior. Glutamate scavenging with pyruvate may be an effective prophylactic and therapeutic option for post-TBI depression by reducing associated elevations in brain glutamate levels.

Assessing Dominant-Submissive Behavior in Adult Rats Following Traumatic Brain Injury.

Competition over resources such as food, territory, and mates significantly influences relationships within animal species and is mediated through social hierarchies that are often based on dominant-submissive relationships. The dominant-submissive relationship is a normal behavioral pattern among the individuals of a species. Traumatic brain injury is a frequent cause of social interaction impairment and the reorganization of dominant-submissive relationships in animal pairs. This protocol describes submissive behavior in adult male Sprague-Dawley rats after the induction of traumatic brain injury using a fluid-percussion model compared to naive rats through a series of dominant-submissive tests performed between 29 days and 33 days after induction. The dominant-submissive behavior test shows how brain injury can induce submissive behavior in animals competing for food. After traumatic brain injury, the rodents were more submissive, as indicated by them spending less time at the feeder and being less likely to arrive first at the trough compared to the control animals. According to this protocol, submissive behavior develops after traumatic brain injury in adult male rats.