The pathophysiology of traumatic brain injury at a glance
TL;DR: Although each case of TBI is unique and affected individuals display different degrees of injury, different regional patterns of injury and different recovery profiles, this review and accompanying poster aim to illustrate some of the common underlying neurochemical and metabolic responses to TBI.
Abstract: Traumatic brain injury (TBI) is defined as an impact, penetration or rapid movement of the brain within the skull that results in altered mental state. TBI occurs more than any other disease, including breast cancer, AIDS, Parkinson’s disease and multiple sclerosis, and affects all age groups and both genders. In the US and Europe, the magnitude of this epidemic has drawn national attention owing to the publicity received by injured athletes and military personnel. This increased public awareness has uncovered a number of unanswered questions concerning TBI, and we are increasingly aware of the lack of treatment options for a crisis that affects millions. Although each case of TBI is unique and affected individuals display different degrees of injury, different regional patterns of injury and different recovery profiles, this review and accompanying poster aim to illustrate some of the common underlying neurochemical and metabolic responses to TBI. Recognition of these recurrent features could allow elucidation of potential therapeutic targets for early intervention.
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TL;DR: The current state of knowledge of physiological role and function of microglia during brain development and in the mature brain is summarized and microglial contribution to brain pathologies such as Alzheimer's and Parkinson’s disease, brain ischemia, traumatic brain injury, brain tumor as well as neuropsychiatric diseases are highlighted.
Abstract: Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult to the CNS homeostasis. Although microglia have long been recognized as a crucial player in generating and maintaining inflammatory responses in the CNS, now it has become clear, that their function are much more diverse, particularly in the healthy brain. The innate immune response and phagocytosis represent only a little segment of microglia functional repertoire that also includes maintenance of biochemical homeostasis, neuronal circuit maturation during development and experience-dependent remodeling of neuronal circuits in the adult brain. Being equipped by numerous receptors and cell surface molecules microglia can perform bidirectional interactions with other cell types in the CNS. There is accumulating evidence showing that neurons inform microglia about their status and thus are capable of controlling microglial activation and motility while microglia also modulate neuronal activities. This review addresses the topic: how microglia communicate with other cell types in the brain, including fractalkine signaling, secreted soluble factors and extracellular vesicles. We summarize the current state of knowledge of physiological role and function of microglia during brain development and in the mature brain and further highlight microglial contribution to brain pathologies such as Alzheimer’s and Parkinson’s disease, brain ischemia, traumatic brain injury, brain tumor as well as neuropsychiatric diseases (depression, bipolar disorder, and schizophrenia).
295 citations
Cites background from "The pathophysiology of traumatic br..."
...The primary injury of TBIs, caused by trauma to the head which for example might stretch, compress or tear blood vessels and axons, is not the only reason why patients die or are disabled (Prins et al., 2013)....
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..., activation of microglia and subsequent recruitment of peripheral leukocytes (Prins et al., 2013; Donat et al., 2017; Saber et al., 2017)....
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TL;DR: NIR in the power range of 10–15 W at 810 and 980 nm can provide fluence within the range shown to be biologically beneficial at 3 cm depth, and is reviewed in the context of the literature on low-power NIR penetration.
Abstract: Traumatic brain injury (TBI) is a growing health concern effecting civilians and military personnel. Research has yielded a better understanding of the pathophysiology of TBI, but effective treatments have not been forthcoming. Near-infrared light (NIR) has shown promise in animal models of both TBI and stroke. Yet, it remains unclear if sufficient photonic energy can be delivered to the human brain to yield a beneficial effect. This paper reviews the pathophysiology of TBI and elaborates the physiological effects of NIR in the context of this pathophysiology. Pertinent aspects of the physical properties of NIR, particularly in regards to its interactions with tissue, provide the background for understanding this critical issue of light penetration through tissue. Our recent tissue studies demonstrate no penetration of low level NIR energy through 2 mm of skin or 3 cm of skull and brain. However, at 10-15 W, 0.45%-2.90% of 810 nm light penetrated 3 cm of tissue. A 15 W 810 nm device (continuous or non-pulsed) NIR delivered 2.9% of the surface power density. Pulsing at 10 Hz reduced the dose of light delivered to the surface by 50%, but 2.4% of the surface energy reached the depth of 3 cm. Approximately 1.22% of the energy of 980 nm light at 10-15 W penetrated to 3 cm. These data are reviewed in the context of the literature on low-power NIR penetration, wherein less than half of 1% of the surface energy could reach a depth of 1 cm. NIR in the power range of 10-15 W at 810 and 980 nm can provide fluence within the range shown to be biologically beneficial at 3 cm depth. A companion paper reviews the clinical data on the treatment of patients with chronic TBI in the context of the current literature.
279 citations
Cites background from "The pathophysiology of traumatic br..."
...This energy crisis promotes the increased concentration of free radicals, due to increased pentose phosphate metabolism, reduced mitochondrial function, and impaired free radical scavenger mechanisms.(19) The consequences of increased free radicals can be far-reaching including propagation of additional free radicals, breakdown of lipids within membranes,(34) edema, inflammation, and DNA damage....
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...An early event is increased release of potassium which is proportional to the severity of the injury.(19) This has a robust inhibitory effect on neuronal activity....
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TL;DR: This article strengthens the recent pathophysiological sight of TBI mainly attention on oxidative stress, excitotoxicity, cerebral oxygenation and cerebral blood flow (CBF), development of edema, and inflammatory activities.
Abstract: Background Traumatic brain injury (TBI) constitutes the primary reason for mortality and morbidity in persons worldwide below 45 years of age. 1.7 million Traumatic events occur yearly in the United States alone, considering for 50,000 deaths. In severe traumatic brain injury sufferers, a considerable achievement attained in treating short-term consequences; but till date, huge failures are occurring in researcher's capability to render severe traumatic brain injury sufferers to an elevated degree of performing. Methods Initial damage force results in Primary brain injury, causing tissue destruction and distortion in the early post-injury period. These secondary injuries from TBI cause changes in cell performance and dissemination of trauma via activities like free-radical generation, depolarization, and formation of edema, excitotoxicity, and disruption of blood brain barrier, calcium homeostasis, and intracranial hematoma. The expectation for developing effect in TBI sufferers is the best knowledge of these activities and enhancement of remedies that restrict secondary brain damage. Results The focal point of this study is on knowing the complex outburst of secondary impairments and studying the pathophysiology of TBI which provides alternative treatment benefits. Conclusion While injured persons demonstrate dissimilar levels of harm and every case is novel with specific recovery profiles, this article strengthens the recent pathophysiological sight of TBI mainly attention on oxidative stress, excitotoxicity, cerebral oxygenation and cerebral blood flow (CBF), development of edema, and inflammatory activities. For initial research acknowledgment of these recurring factors could permit clarification of possible beneficial targets.
194 citations
TL;DR: This new work shows how a tau-sensitive brain imaging agent, [F-18]FDDNP, may be able to detect the disease in living people with varying degrees of symptoms of chronic traumatic encephalopathy, and suggests the presence of neuropathological patterns consistent with models of concussion.
Abstract: Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer’s dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.
183 citations
Cites background from "The pathophysiology of traumatic br..."
...Focal types of brain injury such as contusions or lacerations that commonly occur in moderate and severe traumatic injuries in humans or primate models of traumatic brain injury (27, 31, 32) are only rarely reported in concussions (33)....
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TL;DR: Books on potential mechanisms of damage following repeated mTBI are covered, integrating known mechanisms of pathology underlying moderate–severe TBIs, with recent studies on adult rodent models relevant to direct impact injuries rather than blast-induced damage.
156 citations
References
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01 Mar 2010
2,896 citations
"The pathophysiology of traumatic br..." refers background in this paper
...These events are responsible for 50,000 deaths, leave 80,000 individuals with permanent disabilities and cost more than US$77 billion on average per year (Faul et al., 2010)....
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...%) are the leading causes of moderate to severe TBI in the US (Faul et al., 2010)....
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01 Jan 2006
2,565 citations
"The pathophysiology of traumatic br..." refers background in this paper
...These events are responsible for 50,000 deaths, leave 80,000 individuals with permanent disabilities and cost more than US$77 billion on average per year (Faul et al., 2010)....
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...%) are the leading causes of moderate to severe TBI in the US (Faul et al., 2010)....
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TL;DR: This work reviews 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 professionalathletes, 1 football player and 2 boxers.
Abstract: Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.
2,049 citations
"The pathophysiology of traumatic br..." refers background in this paper
...Furthermore, there is evidence to suggest that moderate to severe TBI, and even repeat mild TBI, might be associated with increased risk of neurodegenerative diseases such as Alzheimer’s disease (Lye and Shores, 2000), chronic traumatic encephalopathy (McKee et al., 2009) and Parkinson’s disease (Hutson et al....
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...…evidence to suggest that moderate to severe TBI, and even repeat mild TBI, might be associated with increased risk of neurodegenerative diseases such as Alzheimer’s disease (Lye and Shores, 2000), chronic traumatic encephalopathy (McKee et al., 2009) and Parkinson’s disease (Hutson et al., 2011)....
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TL;DR: Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that beta-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism.
Abstract: Catheterization of cerebral vessels in three obese patients undergoing 5-6 wk of starvation demonstrated that beta-hydroxybutyrate and acetoacetate replaced glucose as the predominant fuel for brain metabolism. A strikingly low respiratory quotient was also observed, suggesting a carboxylation mechanism as a means of disposing of some of the carbon of the consumed substrates.
1,465 citations
"The pathophysiology of traumatic br..." refers background in this paper
..., 1986; Kreis and Ross, 1992), hyperketonemia (Owen et al., 1967; Sokoloff 1973), ischemia (Vannucci and Vannucci, 2000), diabetes (Wahren et al....
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...…its reliance on alternative substrates under conditions of energy stress [starvation (Dahlquist and Persson, 1976; Hawkins, 1971; Hawkins et al., 1986; Kreis and Ross, 1992), hyperketonemia (Owen et al., 1967; Sokoloff 1973), ischemia (Vannucci and Vannucci, 2000), diabetes (Wahren et al., 1999)]....
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TL;DR: It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.
Abstract: This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.
1,193 citations
"The pathophysiology of traumatic br..." refers background in this paper
...Increases in markers of lipid peroxidation have been observed 1-24 hours after weight-drop (Hsiang et al., 1997; Marmarou et al., 1994; Vagnozzi et al., 1999; Lewén and Hillered, 1998; Tyurin et al., 2000) and CCI (Singh et al., 2006) injury....
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