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Cells Dec 2020Perinatal brain injury or neonatal encephalopathy (NE) is a state of disturbed neurological function in neonates, caused by a number of different aetiologies. The most... (Review)
Review
Perinatal brain injury or neonatal encephalopathy (NE) is a state of disturbed neurological function in neonates, caused by a number of different aetiologies. The most prominent cause of NE is hypoxic ischaemic encephalopathy, which can often induce seizures. NE and neonatal seizures are both associated with poor neurological outcomes, resulting in conditions such as cerebral palsy, epilepsy, autism, schizophrenia and intellectual disability. The current treatment strategies for NE and neonatal seizures have suboptimal success in effectively treating neonates. Therapeutic hypothermia is currently used to treat NE and has been shown to reduce morbidity and has neuroprotective effects. However, its success varies between developed and developing countries, most likely as a result of lack of sufficient resources. The first-line pharmacological treatment for NE is phenobarbital, followed by phenytoin, fosphenytoin and lidocaine as second-line treatments. While these drugs are mostly effective at halting seizure activity, they are associated with long-lasting adverse neurological effects on development. Over the last years, inflammation has been recognized as a trigger of NE and seizures, and evidence has indicated that this inflammation plays a role in the long-term neuronal damage experienced by survivors. Researchers are therefore investigating the possible neuroprotective effects that could be achieved by using anti-inflammatory drugs in the treatment of NE. In this review we will highlight the current knowledge of the inflammatory response after perinatal brain injury and what we can learn from animal models.
Topics: Animals; Brain Injuries; Cytokines; Disease Models, Animal; Female; Inflammation; Microglia; Pregnancy; Receptors, Purinergic; Toll-Like Receptors
PubMed: 33302543
DOI: 10.3390/cells9122640 -
Current Neurology and Neuroscience... Feb 2021Increasingly sophisticated systems for monitoring the brain have led to an increase in the use of multimodality monitoring (MMM) to detect secondary brain injuries... (Review)
Review
PURPOSE OF REVIEW
Increasingly sophisticated systems for monitoring the brain have led to an increase in the use of multimodality monitoring (MMM) to detect secondary brain injuries before irreversible damage occurs after brain trauma. This review examines the challenges and opportunities associated with MMM in this population.
RECENT FINDINGS
Locally and internationally, the use of MMM varies. Practical challenges include difficulties with data acquisition, curation, and harmonization with other data sources limiting collaboration. However, efforts toward integration of MMM data, advancements in data science, and the availability of cloud-based infrastructures are now affording the opportunity for MMM to advance the care of patients with brain trauma. MMM provides data to guide the precision management of patients with traumatic brain injury in real time. While challenges exist, there are exciting opportunities for MMM to live up to this promise and to drive new insights into the physiology of the brain and beyond.
Topics: Brain; Brain Injuries; Brain Injuries, Traumatic; Data Science; Humans; Intracranial Pressure; Monitoring, Physiologic
PubMed: 33527217
DOI: 10.1007/s11910-021-01098-y -
Current Neurology and Neuroscience... Aug 2019Over the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the... (Review)
Review
PURPOSE OF REVIEW
Over the last years, the focus of clinical and animal research in subarachnoid hemorrhage (SAH) shifted towards the early phase after the bleeding based on the association of the early injury pattern (first 72 h) with secondary complications and poor outcome. This phase is commonly referenced as early brain injury (EBI). In this clinical review, we intended to overview commonly used definitions of EBI, underlying mechanisms, and potential treatment implications.
RECENT FINDINGS
We found a large heterogeneity in the definition used for EBI comprising clinical symptoms, neuroimaging parameters, and advanced neuromonitoring techniques. Although specific treatments are currently not available, therapeutic interventions are aimed at ameliorating EBI by improving the energy/supply mismatch in the early phase after SAH. Future research integrating brain-derived biomarkers is warranted to improve our pathophysiologic understanding of EBI in order to ameliorate early injury patterns and improve patients' outcomes.
Topics: Animals; Brain Injuries; Early Diagnosis; Humans; Subarachnoid Hemorrhage; Terminology as Topic
PubMed: 31468197
DOI: 10.1007/s11910-019-0990-3 -
Current Opinion in Anaesthesiology Oct 2022Outcome following traumatic brain injury (TBI) remains variable, and derangements in cerebral metabolism are a common finding in patients with poor outcome. This review... (Review)
Review
PURPOSE OF REVIEW
Outcome following traumatic brain injury (TBI) remains variable, and derangements in cerebral metabolism are a common finding in patients with poor outcome. This review compares our understanding of cerebral metabolism in health with derangements seen following TBI.
RECENT FINDINGS
Ischemia is common within the first 24 h of injury and inconsistently detected by bedside monitoring. Metabolic derangements can also result from tissue hypoxia in the absence of ischemic reductions in blood flow due to microvascular ischemia and mitochondrial dysfunction. Glucose delivery across the injured brain is dependent on blood glucose and regional cerebral blood flow, and is an important contributor to derangements in glucose metabolism. Alternative energy substrates such as lactate, ketone bodies and succinate that may support mitochondrial function, and can be utilized when glucose availability is low, have been studied following TBI but require further investigation.
SUMMARY
Mitochondrial dysfunction and the use of alternative energy substrates are potential therapeutic targets, but improved understanding of the causes, impact and significance of metabolic derangements in clinical TBI are needed. Maintaining adequate oxygen and glucose delivery across the injured brain may accelerate the recovery of mitochondrial function and cerebral energy metabolism and remain important management targets.
Topics: Brain; Brain Injuries; Brain Injuries, Traumatic; Cerebrovascular Circulation; Energy Metabolism; Glucose; Humans
PubMed: 35943124
DOI: 10.1097/ACO.0000000000001183 -
Italian Journal of Pediatrics Jul 2020Preterm infants have an increased risk of cognitive and behavioral deficits and cerebral palsy compared to term born babies. Especially before 32 weeks of gestation,... (Review)
Review
Preterm infants have an increased risk of cognitive and behavioral deficits and cerebral palsy compared to term born babies. Especially before 32 weeks of gestation, infants may require respiratory support, but at the same time, ventilation is known to induce oxidative stress, increasing the risk of brain injury. Ventilation may cause brain damage through two pathways: localized cerebral inflammatory response and hemodynamic instability. During ventilation, the most important causes of pro-inflammatory cytokine release are oxygen toxicity, barotrauma and volutrauma. The purpose of this review was to analyze the mechanism of ventilation-induced lung injury (VILI) and the relationship between brain injury and VILI in order to provide the safest possible respiratory support to a premature baby. As gentle ventilation from the delivery room is needed to reduce VILI, it is recommended to start ventilation with 21-30% oxygen, prefer a non-invasive respiratory approach and, if mechanical ventilation is required, prefer low Positive End-Expiratory Pressure and tidal volume.
Topics: Brain Injuries; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Oxidative Stress; Respiration, Artificial; Ventilator-Induced Lung Injury
PubMed: 32703261
DOI: 10.1186/s13052-020-00852-1 -
Biochemical and Biophysical Research... Jul 2023Traumatic brain injury (TBI) can negatively impact systemic organs, which can lead to more death and disability. However, the mechanism underlying the effect of TBI on...
Traumatic brain injury (TBI) can negatively impact systemic organs, which can lead to more death and disability. However, the mechanism underlying the effect of TBI on systemic organs remains unclear. In previous work, we found that brain-derived extracellular vesicles (BDEVs) released from the injured brain can induce systemic coagulation with a widespread fibrin deposition in the microvasculature of the lungs, kidney, and heart in a mouse model of TBI. In this study, we investigated whether BDEVs can induce heart, lung, liver, and kidney injury in TBI mice. The results of pathological staining and related biomarkers indicated that BDEVs can induce histological damage and systematic dysfunction. In vivo imaging system demonstrated that BDEVs can gather in systemic organs. We also found that BDEVs could induce cell apoptosis in the lung, liver, heart, and kidney. Furthermore, we discovered that BDEVs could cause multi-organ endothelial cell damage. Finally, this secondary multi-organ damage could be relieved by removing circulating BDEVs. Our research provides a novel perspective and potential mechanism of TBI-associated multi-organ damage.
Topics: Mice; Animals; Brain Injuries, Traumatic; Brain; Brain Injuries; Apoptosis; Extracellular Vesicles
PubMed: 37163934
DOI: 10.1016/j.bbrc.2023.04.119 -
Brain : a Journal of Neurology Aug 2022Long-term outcomes are difficult to predict after paediatric traumatic brain injury. The presence or absence of focal brain injuries often do not explain cognitive,...
Long-term outcomes are difficult to predict after paediatric traumatic brain injury. The presence or absence of focal brain injuries often do not explain cognitive, emotional and behavioural disabilities that are common and disabling. In adults, traumatic brain injury produces progressive brain atrophy that can be accurately measured and is associated with cognitive decline. However, the effect of paediatric traumatic brain injury on brain volumes is more challenging to measure because of its interaction with normal brain development. Here we report a robust approach to the individualized estimation of brain volume following paediatric traumatic brain injury and investigate its relationship to clinical outcomes. We first used a large healthy control dataset (n > 1200, age 8-22) to describe the healthy development of white and grey matter regions through adolescence. Individual estimates of grey and white matter regional volume were then generated for a group of moderate/severe traumatic brain injury patients injured in childhood (n = 39, mean age 13.53 ± 1.76, median time since injury = 14 months, range 4-168 months) by comparing brain volumes in patients to age-matched controls. Patients were individually classified as having low or normal brain volume. Neuropsychological and neuropsychiatric outcomes were assessed using standardized testing and parent/carer assessments. Relative to head size, grey matter regions decreased in volume during normal adolescence development whereas white matter tracts increased in volume. Traumatic brain injury disrupted healthy brain development, producing reductions in both grey and white matter brain volumes after correcting for age. Of the 39 patients investigated, 11 (28%) had at least one white matter tract with reduced volume and seven (18%) at least one area of grey matter with reduced volume. Those classified as having low brain volume had slower processing speed compared to healthy controls, emotional impairments, higher levels of apathy, increased anger and learning difficulties. In contrast, the presence of focal brain injury and microbleeds were not associated with an increased risk of these clinical impairments. In summary, we show how brain volume abnormalities after paediatric traumatic brain injury can be robustly calculated from individual T1 MRI using a large normative dataset that allows the effects of healthy brain development to be controlled for. Using this approach, we show that volumetric abnormalities are common after moderate/severe traumatic brain injury in both grey and white matter regions, and are associated with higher levels of cognitive, emotional and behavioural abnormalities that are common after paediatric traumatic brain injury.
Topics: Adolescent; Adult; Atrophy; Brain; Brain Injuries; Brain Injuries, Traumatic; Child; Gray Matter; Humans; Magnetic Resonance Imaging; Nervous System Malformations; White Matter; Young Adult
PubMed: 35798350
DOI: 10.1093/brain/awac130 -
Current Neuropharmacology 2021Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages... (Review)
Review
Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage- such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in the inhibition of secondary brain injury can result as a potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in the clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies based on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.
Topics: Brain; Brain Edema; Brain Injuries; Brain Injuries, Traumatic; Humans; Neuroprotective Agents
PubMed: 33632101
DOI: 10.2174/1570159X19666210225145957 -
ELife Feb 2021Zebrafish larvae models can be used to study the link between seizures and the neurodegeneration that follows brain trauma.
Zebrafish larvae models can be used to study the link between seizures and the neurodegeneration that follows brain trauma.
Topics: Animals; Brain Injuries, Traumatic; Epilepsy, Post-Traumatic; Seizures; Zebrafish
PubMed: 33527900
DOI: 10.7554/eLife.65676 -
International Journal of Molecular... Apr 2023Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the... (Review)
Review
Mild traumatic brain injury (mTBI) accounts for approximately 80% of all TBI cases and is a growing source of morbidity and mortality worldwide. To improve the management of children and adults with mTBI, a series of candidate biomarkers have been investigated in recent years. In this context, the measurement of blood biomarkers in the acute phase after a traumatic event helps reduce unnecessary CT scans and hospitalizations. In athletes, improved management of sports-related concussions is also sought to ensure athletes' safety. S100B protein has emerged as the most widely studied and used biomarker for clinical decision making in patients with mTBI. In addition to its use as a diagnostic biomarker, S100B plays an active role in the molecular pathogenic processes accompanying acute brain injury. This review describes S100B protein as a diagnostic tool as well as a potential therapeutic target in patients with mTBI.
Topics: Child; Adult; Humans; Brain Concussion; Brain Injuries; S100 Calcium Binding Protein beta Subunit; Tomography, X-Ray Computed; Biomarkers
PubMed: 37047574
DOI: 10.3390/ijms24076602