A Model of Metabolic Supply-Demand Mismatch Leading to Secondary Brain Injury

2021 ◽  
Author(s):  
Jiangling Song ◽  
Jennifer A. Kim ◽  
Aaron Frank Struck ◽  
Rui Zhang ◽  
M. Brandon Westover
Keyword(s):  
Brain Injury ◽  
Mechanistic Model ◽  
Acute Brain Injury ◽  
Extracellular Potassium ◽  
Secondary Brain Injury ◽  
Proposed Model ◽  
The Common ◽  
High Level ◽  
The Brain ◽  
Common Association

Secondary brain injury (SBI) is defined as new or worsening injury to the brain after an initial neurologic insult, such as hemorrhage, trauma, ischemic stroke, or infection. It is a common and potentially preventable complication following many types of primary brain injury (PBI). However, mechanistic details about how PBI leads to additional brain injury and evolves into SBI are poorly characterized. In this work, we propose a mechanistic model for the metabolic supply demand mismatch hypothesis (MSDMH) of SBI. Our model, based on the Hodgkin-Huxley model, supplemented with additional dynamics for extracellular potassium, oxygen concentration and excitotoxity, provides a high-level unified explanation for why patients with acute brain injury frequently develop SBI. We investigate how decreased oxygen, increased extracellular potassium, excitotoxicity, and seizures can induce SBI, and suggest three underlying paths for how events following PBI may lead to SBI. The proposed model also helps explain several important empirical observations, including the common association of acute brain injury with seizures, the association of seizures with tissue hypoxia and so on. In contrast to current practices which assume that ischemia plays the predominant role in SBI, our model suggests that metabolic crisis involved in SBI can also be non-ischemic. Our findings offer a more comprehensive understanding of the complex interrelationship among potassium, oxygen, excitotoxicity, seizures and SBI.

Use of hemoglobin-based oxygen-carrying solution–201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage

2008 ◽  
Vol 108 (3) ◽  
pp. 575-587 ◽  
Author(s):  
Guy Rosenthal ◽  
Diane Morabito ◽  
Mitchell Cohen ◽  
Annina Roeytenberg ◽  
Nikita Derugin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mr Imaging ◽  
Swine Model ◽  
Secondary Brain Injury ◽  
Large Animal ◽  
Fluoro Jade B ◽  
Significant Difference ◽  
Impact Injury ◽  
The Brain

Object Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. Methods Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. Results Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. Conclusions The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia*

2005 ◽  
Vol 33 (3) ◽  
pp. 661-666 ◽  
Author(s):  
J Andrew McKee ◽  
Randall P. Brewer ◽  
Gary E. Macy ◽  
Barbara Phillips-Bute ◽  
Kurt A. Campbell ◽  
...  
Keyword(s):  
Brain Injury ◽  
Magnesium Sulfate ◽  
Acute Brain Injury ◽  
The Brain

scholarly journals Young plasma ameliorates aging-related acute brain injury after intracerebral hemorrhage

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Jun-Jie Yuan ◽  
Qin Zhang ◽  
Chang-Xiong Gong ◽  
Fa-Xiang Wang ◽  
Jia-Cheng Huang ◽  
...  
Keyword(s):  
Brain Injury ◽  
Intracerebral Hemorrhage ◽  
Brain Damage ◽  
Mrna Level ◽  
Acute Brain Injury ◽  
Aging Brain ◽  
Neural Cells ◽  
Neuroprotective Effects ◽  
The Brain ◽  
Brain Tissues

Abstract Aging has been shown to contribute to both the declined biofunctions of aging brain and aggravation of acute brain damage, and the former could be reversed by young plasma. These results suggest that young plasma treatment may also reduce the acute brain damage induced by intracerebral hemorrhage (ICH). In the present study, we first found that the administration of young plasma significantly reduced the mortality and neurological deficit score in aging ICH rodents, which might be due to the decreased brain water content, damaged neural cells, and increased survival neurons around the perihematomal brain tissues. Then, proteomics analysis was used to screen out the potential neuroprotective circulating factors and the results showed that many factors were changed in health human plasma among young, adult, and old population. Among these significantly changed factors, the plasma insulin-like growth factor 1 (IGF-1) level was significantly decreased with age, which was further confirmed both in human and rats detected by ELISA. Additionally, the brain IGF-1 protein level in aging ICH rats was markedly decreased when compared with young rats. Interestingly, the relative decreased brain IGF-1 level was reversed by the treatment of young plasma in aging ICH rats, while the mRNA level was non-significantly changed. Furthermore, the IGF-1 administration significantly ameliorated the acute brain injury in aging ICH rats. These results indicated that young circulating factors, like IGF-1, may enter brain tissues to exert neuroprotective effects, and young plasma may be considered as a novel therapeutic approach for the clinical treatment of aging-related acute brain injury.

scholarly journals Analysis of Neuron Specific Enolase Serum Levels in Traumatic Brain Injury

2021 ◽  
Vol 5 (4) ◽  
pp. 1218-1222
Author(s):  
Yuliarni Syafrita ◽  
Nora Fitri
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Injuries ◽  
Neuron Specific Enolase ◽  
Serum Levels ◽  
Pathological Process ◽  
P Value ◽  
Secondary Brain Injury ◽  
Post Injury ◽  
The Brain

Background : Traumatic brain injury is still the main cause of death and disability in productive age. Assessment the level of consciousness and imaging examinations after a brain injury can not always describe the severity of damage in the brain, this is because the pathological process is still ongoing due to secondary brain injury. Therefore, it is necessary to examine biomarkers that can describe the severity of the pathological process that occurs. The purpose of this study was to assess serum neuron-specific enolase (NSE) levels and their relationship to the severity and outcome of a traumatic brain injury. Methods : A cross sectional design was conducted in the emergency department of DR M Djamil Hospital, Padang. There were 72 patients who met the inclusion criteria. A Glasgow Coma Scale examination was performed to assess the severity of brain injury and examination of NSE serum levels at 48 hours post- injury using ELISA technique and assess the Glasgow outcome scale (GOS) at 6 weeks post-injury. Data analysis using SPSS 22 program, the results are significance if the p value <0.05  Results : The average NSE level was higher in severe brain injuries than moderate and mild brain injuries and this difference was statistically significant (p<0.05).  The NSE serum levels were higher in poor outcomes than in good outcomes and this difference was statistically significant (p<0.05).  Conclusion : High NSE serum levels in the acute phase were associated with the severity of the brain injury and poor outcome 6 weeks after the brain injury. 

scholarly journals Pathophysiology of severe traumatic brain injury and management of intracranial hypertension

2019 ◽  
Vol 18 (2) ◽  
pp. 62-71
Author(s):  
Raimondas Juškys ◽  
Vaiva Hendrixson
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Intracranial Hypertension ◽  
Severe Traumatic Brain Injury ◽  
Current Treatment ◽  
Secondary Brain Injury ◽  
Management Options ◽  
Treatment Protocols ◽  
Improved Outcomes ◽  
The Brain

It is well recognized that severe traumatic brain injury causes major health and socioeconomic burdens for patients their families and society itself. Over the past decade, understanding of secondary brain injury processes has increased tremendously, permitting implementation of new neurocritical methods of care that substantially contribute to improved outcomes of such patients. The main objective of current treatment protocols is to optimize different physiological measurements that prevent secondary insults and reinforce the ability of the brain to heal. The aim of this literature review is to uncover the pathophysiological mechanisms of severe traumatic brain injury and their interrelationship, including cerebral metabolic crisis, disturbances of blood flow to the brain and development of edema, putting emphasis on intracranial hypertension and its current management options.

scholarly journals Ketamine for critically ill patients with severe acute brain injury: Protocol for a systematic review with meta-analysis and Trial Sequential Analysis of randomised clinical trials

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259899
Author(s):  
Frederik Andreas Madsen ◽  
Trine Hjorslev Andreasen ◽  
Jane Lindschou ◽  
Christian Gluud ◽  
Kirsten Møller
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Brain Injury ◽  
Functional Outcome ◽  
Sequential Analysis ◽  
Acute Brain Injury ◽  
Randomised Clinical Trials ◽  
Trial Sequential Analysis ◽  
Secondary Brain Injury ◽  
Serious Adverse Events

Introduction Intensive care for patients with severe acute brain injury aims both to treat the immediate consequences of the injury and to prevent and treat secondary brain injury to ensure a good functional outcome. Sedation may be used to facilitate mechanical ventilation, for treating agitation, and for controlling intracranial pressure. Ketamine is an N-methyl-D-aspartate receptor antagonist with sedative, analgesic, and potentially neuroprotective properties. We describe a protocol for a systematic review of randomised clinical trials assessing the beneficial and harmful effects of ketamine for patients with severe acute brain injury. Methods and analysis We will systematically search international databases for randomised clinical trials, including CENTRAL, MEDLINE, Embase, and trial registries. Two authors will independently review and select trials for inclusion, and extract data. We will compare ketamine by any regimen versus placebo, no intervention, or other sedatives or analgesics for patients with severe acute brain injury. The primary outcomes will be functional outcome at maximal follow up, quality of life, and serious adverse events. We will also assess secondary and exploratory outcomes. The extracted data will be analysed using Review Manager and Trials Sequential Analysis. Evidence certainty will be graded using GRADE. Ethics and dissemination The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice. PROSPERO no CRD42021210447.

Assistive Technology for Cognition Following Brain Injury: A Clinician's Perspective

2013 ◽  
Vol 23 (2) ◽  
pp. 74-83 ◽  
Author(s):  
Mary Pat Daly
Keyword(s):  
Brain Injury ◽  
Assistive Technology ◽  
Day Treatment ◽  
Cognitive Impairments ◽  
Acute Care Hospital ◽  
Care Hospital ◽  
Injury Rehabilitation ◽  
High Level ◽  
The Brain ◽  
And Training

Whether working in a specialized brain injury program, outpatient clinic, acute care hospital, or private practice, speech-language pathologists serving adults with cognitive impairments due to acquired brain injury (ABI) are faced with many challenges: assessment, treatment planning, client and family education, documentation, team conferences, and billing. The combination of these demands requires a high level of efficiency. Include the rapidly expanding field of assistive technology for cognition (ATC) — cell phones, smart phones, tablets, and apps used to compensate for cognitive impairments — and the most experienced and adept clinician can feel overwhelmed. This article describes the practical application of ATC assessment and training in the brain injury day treatment program at the Brain Injury Rehabilitation Center (BIRC), Portland, OR, across three domains: (a) a clinician’s perceptions of ATC and its integration into clinical practice, (b) selected ATC assessment processes and training techniques, and (c) challenges associated with the implementation of ATC in a clinical setting.

scholarly journals A Sphingosine-1-Phosphate Receptor Modulator Attenuated Secondary Brain Injury and Improved Neurological Functions of Mice after ICH

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
T. Bobinger ◽  
T. Bäuerle ◽  
L. Seyler ◽  
S. v Horsten ◽  
S. Schwab ◽  
...  
Keyword(s):  
Brain Injury ◽  
Acute Stage ◽  
Secondary Brain Injury ◽  
Protective Effects ◽  
Receptor Modulator ◽  
Receptor Modulation ◽  
Short Term Study ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
The Brain

Background. Stroke activates the immune system and induces brain infiltration by immune cells, aggravating brain injury. Poststroke immunomodulation via (S1P-)receptor modulation is beneficial; however, the S1P-modulator in clinical use (FTY-720) is unspecific, and undesirable side effects have been reported. Previously, we tested effects of a novel selective S1P-receptor modulator, Siponimod, on ICH-induced brain injury in acute stage of the disease. In the current study, we investigated whether protective effects of Siponimod, evaluated in a short-term study, will protect the brain of ICH animals at long term as well. Methods. 134 C57BL/6N mice were divided into sham and ICH-operated groups. Collagenase model of ICH was employed. ICH animals were divided into Siponimod treated and nontreated. Dose- and time-dependent effects of Siponimod were investigated. Contraplay between development of brain injury and the number of lymphocytes infiltrating the brain was investigated by forelimb placing, T-Maze test, brain water content calculation, MRI scanning, and immunostaining. Results. Depending on the therapeutic strategy, Siponimod attenuated the development of brain edema, decreased ICH-induced ventriculomegaly and improved neurological functions of animals after ICH. It was associated with less lymphocytes in the brain of ICH animals. Conclusion. Siponimod is able to decrease the brain injury and improves neurological functions of animals after ICH.

scholarly journals The Systemic and Local Acute Phase Response following Acute Brain Injury

2002 ◽  
Vol 22 (3) ◽  
pp. 318-326 ◽  
Author(s):  
David C. Wilcockson ◽  
Sandra J. Campbell ◽  
Daniel C. Anthony ◽  
V. Hugh Perry
Keyword(s):  
Brain Injury ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Brain Lesion ◽  
Acute Brain Injury ◽  
Phase Response ◽  
Acute Injury ◽  
Polymerase Chain ◽  
The Brain ◽  
Excitotoxic Lesion

It is not known whether acute brain injury results in a systemic acute phase response (APR) or whether an APR influences outcome after an insult to the CNS. The present study sought to establish whether brain injury elicits a systemic or local APR. The expression of acute phase protein (APP) mRNA in liver and brain tissues was measured by Taqman reverse transcriptase-polymerase chain reaction after an excitotoxic lesion in the striatum or challenge with a proinflammatory cytokine. N-methyl-D-aspartate (NMDA)–induced brain lesion did not elicit a systemic APR. In contrast, proinflammatory challenge with mouse recombinant interleukin-1β (mrIL-1β) resulted in a significant hepatic APP mRNA expression within 6 hours. Thus, an inflammatory challenge that results in a meningitis leads to a hepatic APR, whereas acute brain injury alone, with no evidence of a meningitis, does not produce an APR. This is surprising because NMDA leads to an increase in endogenous IL-1β synthesis. This suggests that the brain has an endogenous antiinflammatory mechanism, which protects against the spread of inflammation after an acute injury. In the brain, both excitotoxic lesions and proinflammatory challenge resulted in a profound parenchymal upregulation of APP mRNA after 6 and 12 hours in the injected hemisphere. These results suggest that the local APR may play a role as an antiinflammatory mechanism. These findings indicate a potentially pivotal role for peripheral and local APP production on outcome after brain injury.

scholarly journals Neurobiological consequences of traumatic brain injury

2011 ◽  
Vol 13 (3) ◽  
pp. 287-300 ◽  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Public Health Problem ◽  
Brain Regions ◽  
Common Clinical Presentation ◽  
The Common ◽  
The Brain ◽  
Chronic Sequelae ◽  
Ca Homeostasis ◽  
Recent Attention

Traumatic brain injury (TBI) is a worldwide public health problem typically caused by contact and inertial forces acting on the brain. Recent attention has also focused on the mechanisms of injury associated with exposure to blast events or explosions. Advances in the understanding of the neuropathophysiology of TBI suggest that these forces initiate an elaborate and complex array of cellular and subcellular events related to alterations in Ca(++) homeostasis and signaling. Furthermore, there is a fairly predictable profile of brain regions that are impacted by neurotrauma and the related events. This profile of brain damage accurately predicts the acute and chronic sequelae that TBI survivors suffer from, although there is enough variation to suggest that individual differences such as genetic polymorphisms and factors governing resiliency play a role in modulating outcome. This paper reviews our current understanding of the neuropathophysiology of TBI and how this relates to the common clinical presentation of neurobehavioral difficulties seen after an injury.

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