Neuroprotective agents in critical illness

Author(s):  
Jerrold L. Perrott ◽  
Steven C. Reynolds

The prevention and reduction of secondary injury following primary CNS insult is an important goal in critically-ill patients. Numerous pharmacological therapies have been studied as potential neuroprotective agents with few translating from research to clinical benefit. These are nimodipine and statins in aneurysmal subarachnoid haemorrhage and phenytoin in traumatic brain injury. Additionally, in traumatic brain injury, clinical studies have identified that corticosteroids and albumin colloid resuscitation are associated with increased risk of mortality, and as such should be avoided. Future research into new pharmacological neuroprotective strategies is warranted.

2013 ◽  
Vol 30 (5) ◽  
pp. 361-366 ◽  
Author(s):  
Ibrahim M. Alharfi ◽  
Tanya Charyk Stewart ◽  
Shawn H. Kelly ◽  
Gavin C. Morrison ◽  
Douglas D. Fraser

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1009
Author(s):  
Delong Qin ◽  
Junmin Wang ◽  
Anh Le ◽  
Tom J. Wang ◽  
Xuemei Chen ◽  
...  

The secondary injury process after traumatic brain injury (TBI) results in motor dysfunction, cognitive and emotional impairment, and poor outcomes. These injury cascades include excitotoxic injury, mitochondrial dysfunction, oxidative stress, ion imbalance, inflammation, and increased vascular permeability. Electron microscopy is an irreplaceable tool to understand the complex pathogenesis of TBI as the secondary injury is usually accompanied by a series of pathologic changes at the ultra-micro level of the brain cells. These changes include the ultrastructural changes in different parts of the neurons (cell body, axon, and synapses), glial cells, and blood–brain barrier, etc. In view of the current difficulties in the treatment of TBI, identifying the changes in subcellular structures can help us better understand the complex pathologic cascade reactions after TBI and improve clinical diagnosis and treatment. The purpose of this review is to summarize and discuss the ultrastructural changes related to neurons (e.g., condensed mitochondrial membrane in ferroptosis), glial cells, and blood–brain barrier in the existing reports of TBI, to deepen the in-depth study of TBI pathomechanism, hoping to provide a future research direction of pathogenesis and treatment, with the ultimate aim of improving the prognosis of patients with TBI.


2021 ◽  
Vol 12 ◽  
Author(s):  
Colleen N. Bodnar ◽  
James B. Watson ◽  
Emma K. Higgins ◽  
Ning Quan ◽  
Adam D. Bachstetter

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI.


2019 ◽  
Author(s):  
Emily L. Dennis ◽  
Karen Caeyenberghs ◽  
Robert F. Asarnow ◽  
Talin Babikian ◽  
Brenda Bartnik-Olson ◽  
...  

Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population; however, research in this population lags behind research in adults. This may be due, in part, to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. Specific developmental issues also warrant attention in studies of children, and the ever-changing context of childhood and adolescence may require larger sample sizes than are commonly available to adequately address remaining questions related to TBI. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate-Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis. In this paper we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. We conclude with recommendations for future research in this field of study.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 886-887
Author(s):  
Andrei Irimia ◽  
Ammar Dharani ◽  
Van Ngo ◽  
David Robles ◽  
Kenneth Rostowsky

Abstract Mild traumatic brain injury (mTBI) affects white matter (WM) integrity and accelerates neurodegeneration. This study assesses the effects of age, sex, and cerebral microbleed (CMB) load as predictors of WM integrity in 70 subjects aged 18-77 imaged acutely and ~6 months after mTBI using diffusion tensor imaging (DTI). Two-tensor unscented Kalman tractography was used to segment and cluster 73 WM structures and to map changes in their mean fractional anisotropy (FA), a surrogate measure of WM integrity. Dimensionality reduction of mean FA feature vectors was implemented using principal component (PC) analysis, and two prominent PCs were used as responses in a multivariate analysis of covariance. Acutely and chronically, older age was significantly associated with lower FA (F2,65 = 8.7, p < .001, η2 = 0.2; F2,65 = 12.3, p < .001, η2 = 0.3, respectively), notably in the corpus callosum and in dorsolateral temporal structures, confirming older adults’ WM vulnerability to mTBI. Chronically, sex was associated with mean FA (F2,65 = 5.0, p = 0.01, η2 = 0.1), indicating males’ greater susceptibility to WM degradation. Acutely, a significant association was observed between CMB load and mean FA (F2,65 = 5.1, p = 0.009, η2 = 0.1), suggesting that CMBs reflect the acute severity of diffuse axonal injury. Together, these findings indicate that older age, male sex, and CMB load are risk factors for WM degeneration. Future research should examine how sex- and age-mediated WM degradation lead to cognitive decline and connectome degeneration after mTBI.


2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 850-851
Author(s):  
Arseniy Yashkin

Abstract The aim of this study was to assess differences in the effect of traumatic brain injury (TBI) on the onset of Alzheimer’s disease (AD) and other dementias between veteran and non-veteran respondents of the Health and Retirement Study as well as to measure the sensitivity of these differences to the introduction of controls for groups of demographic, medical co-morbidity and polygenic risk scores reflecting AD hallmarks. Using the Fine-Gray proportional hazards model we found that TBI was a strong predictor of dementia in community dwelling residents age 65+: for AD associated risk was 181% [Hazard Ratio (HR): 2.81; CI:2.05-3.86] sample-wide and 142% [HR: 2.42; CI:1.31-2.46] in veteran males. Effect magnitude decreased with the addition of risk-related control variables but remained associated with significantly increased risk. Large differences in risk were observed between veteran and non-veteran males for AD, vascular dementia, senile dementia, and dementia with Lewy Bodies


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 586 ◽  
Author(s):  
Hamilton Roschel ◽  
Bruno Gualano ◽  
Sergej M. Ostojic ◽  
Eric S. Rawson

There is a robust and compelling body of evidence supporting the ergogenic and therapeutic role of creatine supplementation in muscle. Beyond these well-described effects and mechanisms, there is literature to suggest that creatine may also be beneficial to brain health (e.g., cognitive processing, brain function, and recovery from trauma). This is a growing field of research, and the purpose of this short review is to provide an update on the effects of creatine supplementation on brain health in humans. There is a potential for creatine supplementation to improve cognitive processing, especially in conditions characterized by brain creatine deficits, which could be induced by acute stressors (e.g., exercise, sleep deprivation) or chronic, pathologic conditions (e.g., creatine synthesis enzyme deficiencies, mild traumatic brain injury, aging, Alzheimer’s disease, depression). Despite this, the optimal creatine protocol able to increase brain creatine levels is still to be determined. Similarly, supplementation studies concomitantly assessing brain creatine and cognitive function are needed. Collectively, data available are promising and future research in the area is warranted.


Brain Injury ◽  
2009 ◽  
Vol 23 (7-8) ◽  
pp. 639-648 ◽  
Author(s):  
Lakshmi Srinivasan ◽  
Brian Roberts ◽  
Tamara Bushnik ◽  
Jeffrey Englander ◽  
David A. Spain ◽  
...  

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e016694 ◽  
Author(s):  
Sareh Zarshenas ◽  
Laetitia Tam ◽  
Angela Colantonio ◽  
Seyed Mohammad Alavinia ◽  
Nora Cullen

IntroductionMany studies have assessed the predictors of morbidity/mortality of patients with traumatic brain injury (TBI) in acute care. However, with the increasing rate of survival after TBI, more attention has been given to discharge destinations from acute care as an important measure of clinical priorities. This study describes the design of a systematic review compiling and synthesising studies on the prognostic factors of discharge settings from acute care in patients with TBI.Methods and analysisThis systematic review will be conducted on peer-reviewed studies using seven databases including Medline/Medline in-Process, Embase, Cochrane Database of Systematic Reviews, Cochrane CENTRAL, PsycINFO, CINAHL and Supplemental PubMed. The reference list of selected articles and Google Scholar will also be reviewed to determine other relevant articles. This study will include all English language observational studies that focus on adult patients with TBI in acute care settings. The quality of articles will be assessed by the Quality in Prognostic Studies tool.Ethics and disseminationThe results of this review will provide evidence that may guide healthcare providers in making more informed and timely discharge decisions to the next level of care for patient with TBI. Also, this study will provide valuable information to address the gaps in knowledge for future research.Trial registration numberTrial registration number (PROSPERO) is CRD42016033046.


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