Temporal profile of serum metabolites and inflammation following closed head injury in rats is associated with HPA axis hyperactivity

Arora, Palkin; Singh, Kavita; Kumari, Megha; Trivedi, Richa

doi:10.1007/s11306-022-01886-8

Cited by 6 publications

(5 citation statements)

References 55 publications

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“…Similarly, LEV treatment was associated with elevated plasma 7d-IL-1β levels, but there was no significant effect of early seizures or LFPI on plasma IL-1β levels. Although seizures 84 and TBI 85 have been associated with elevated plasma IL-1β levels, the literature also presents examples where plasma IL-1β levels, are not elevated after brain trauma 86,87 or may be elevated in some but not all patients with severe TBI. 88 In contrast, early seizures despite LEV treatment, i.e., LEV-resistant early seizures, are predicted by high plasma 2d-IFNγ levels (response biomarker).…”

Section: Discussionmentioning

confidence: 99%

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

et al. 2023

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Objective We used the lateral fluid percussion injury (LFPI) model of moderate‐to‐severe traumatic brain injury (TBI) to identify early plasma biomarkers predicting injury, early post‐traumatic seizures or neuromotor functional recovery (neuroscores), considering the effect of levetiracetam, which is commonly given after severe TBI. Methods Adult male Sprague–Dawley rats underwent left parietal LFPI, received levetiracetam (200 mg/kg bolus, 200 mg/kg/day subcutaneously for 7 days [7d]) or vehicle post‐LFPI, and were continuously video‐EEG recorded (n = 14/group). Sham (craniotomy only, n = 6), and naïve controls (n = 10) were also used. Neuroscores and plasma collection were done at 2d or 7d post‐LFPI or equivalent timepoints in sham/naïve. Plasma protein biomarker levels were determined by reverse phase protein microarray and classified according to injury severity (LFPI vs. sham/control), levetiracetam treatment, early seizures, and 2d‐to‐7d neuroscore recovery, using machine learning. Results Low 2d plasma levels of Thr231‐phosphorylated tau protein (pTAU‐Thr231) and S100B combined (ROC AUC = 0.7790) predicted prior craniotomy surgery (diagnostic biomarker). Levetiracetam‐treated LFPI rats were differentiated from vehicle treated by the 2d‐HMGB1, 2d‐pTAU‐Thr231, and 2d‐UCHL1 plasma levels combined (ROC AUC = 0.9394) (pharmacodynamic biomarker). Levetiracetam prevented the seizure effects on two biomarkers that predicted early seizures only among vehicle‐treated LFPI rats: pTAU‐Thr231 (ROC AUC = 1) and UCHL1 (ROC AUC = 0.8333) (prognostic biomarker of early seizures among vehicle‐treated LFPI rats). Levetiracetam‐resistant early seizures were predicted by high 2d‐IFNγ plasma levels (ROC AUC = 0.8750) (response biomarker). 2d‐to‐7d neuroscore recovery was best predicted by higher 2d‐S100B, lower 2d‐HMGB1, and 2d‐to‐7d increase in HMGB1 or decrease in TNF (P < 0.05) (prognostic biomarkers). Significance Antiseizure medications and early seizures need to be considered in the interpretation of early post‐traumatic biomarkers.

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Section: Discussionmentioning

confidence: 99%

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

et al. 2023

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“…One study using young adult rats who sustained a mild TBI using FPI found that male rats had significantly more microglia present in the PVN compared to Sham controls at 1-week post-injury (Bromberg et al, 2020). Similarly, a study using Marmarou's impact acceleration model found that TBI subjects had more microglia in the hypothalamus at 5, 10, and 30 days post-injury (Arora et al, 2022). Interestingly, there were significantly higher levels of inflammatory marker tumor necrosis factor α in the hypothalamus, pituitary gland, and adrenal glands of subjects who sustained a mild TBI via CCI 1 day and 1-month post-injury (Taheri et al, 2022).…”

Section: The Rodent Hypothalamus Following Adult Tbimentioning

confidence: 99%

“…ACTH levels were similarly elevated 14 days post‐injury (Griesbach et al., 2011). Additionally, another group using Marmarou's impact acceleration model found that increasing severity resulted in increased corticosterone levels more immediately following injury compared to milder injuries (Arora et al., 2022). Though the hypothalamus is nestled among a significant number of other structures in the brain, its central location and interconnectedness with the more fragile pituitary gland results in significant perturbations to the various axes in which it fine‐tunes hormone secretion.…”

Section: The Vulnerable Brainmentioning

confidence: 99%

A strike to the head: Parallels between the pediatric and adult human and the rodent in traumatic brain injury

Smith,

Grayson

2024

J of Neuroscience Research

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Traumatic brain injury (TBI) is a condition that occurs commonly in children from infancy through adolescence and is a global health concern. Pediatric TBI presents with a bimodal age distribution, with very young children (0–4 years) and adolescents (15–19 years) more commonly injured. Because children's brains are still developing, there is increased vulnerability to the effects of head trauma, which results in entirely different patterns of injury than in adults. Pediatric TBI has a profound and lasting impact on a child's development and quality of life, resulting in long‐lasting consequences to physical, cognitive, and emotional development. Chronic issues like learning disabilities, behavioral problems, and emotional disturbances can develop. Early intervention and ongoing support are critical for minimizing these long‐term deficits. Many animal models of TBI exist, and each varies significantly, displaying different characteristics of clinical TBI. The neurodevelopment differs in the rodent from the human in timing and effect, so TBI outcomes in the juvenile rodent can thus vary from the human child. The current review compares findings from preclinical TBI work in juvenile and adult rodents to clinical TBI research in pediatric and adult humans. We focus on the four brain regions most affected by TBI: the prefrontal cortex, corpus callosum, hippocampus, and hypothalamus. Each has its unique developmental projections and thus is impacted by TBI differently. This review aims to compare the healthy neurodevelopment of these four brain regions in humans to the developmental processes in rodents.

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“…It is important that the restoration of metabolism can occur only in some regions of the brain, while other regions are characterized by a decrease in metabolic status over a long period, years after TBI, even in patients with a mild form of this injury [ 241 , 242 ]. The disintegration of functional connections between various brain structures, the decrease in neuronal plasticity in them, and the activation of neuro-inflammatory processes lead to dysfunctions of the CNS and an imbalance of metabolic processes at the periphery [ 243 , 244 , 245 ].…”

Section: Intranasal Insulin and Brain Injurymentioning

confidence: 99%

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

Zorina

Derkach

2023

IJMS

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A decrease in the activity of the insulin signaling system of the brain, due to both central insulin resistance and insulin deficiency, leads to neurodegeneration and impaired regulation of appetite, metabolism, endocrine functions. This is due to the neuroprotective properties of brain insulin and its leading role in maintaining glucose homeostasis in the brain, as well as in the regulation of the brain signaling network responsible for the functioning of the nervous, endocrine, and other systems. One of the approaches to restore the activity of the insulin system of the brain is the use of intranasally administered insulin (INI). Currently, INI is being considered as a promising drug to treat Alzheimer’s disease and mild cognitive impairment. The clinical application of INI is being developed for the treatment of other neurodegenerative diseases and improve cognitive abilities in stress, overwork, and depression. At the same time, much attention has recently been paid to the prospects of using INI for the treatment of cerebral ischemia, traumatic brain injuries, and postoperative delirium (after anesthesia), as well as diabetes mellitus and its complications, including dysfunctions in the gonadal and thyroid axes. This review is devoted to the prospects and current trends in the use of INI for the treatment of these diseases, which, although differing in etiology and pathogenesis, are characterized by impaired insulin signaling in the brain.

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Temporal profile of serum metabolites and inflammation following closed head injury in rats is associated with HPA axis hyperactivity

Cited by 6 publications

References 55 publications

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

Early preclinical plasma protein biomarkers of brain trauma are influenced by early seizures and levetiracetam

A strike to the head: Parallels between the pediatric and adult human and the rodent in traumatic brain injury

Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium

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