Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion

Harish, G.; Mahadevan, Anita; Pruthi, Nupur; Sreenivasamurthy, Sreelakshmi K.; Puttamallesh, Vinuth N; Prasad, T. S. Keshava; Shankar, Susarla Krishna; Bharath, M. M. Srinivas

doi:10.1111/jnc.13082

Cited by 83 publications

(78 citation statements)

References 85 publications

(87 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, secondary brain injury develops and progresses in the “traumatic penumbra”, that is the potentially salvageable brain tissue surrounding the primary lesion [45,46]. There is evidence that focal necrosis increases over time and the volume of necrotic tissue can reach 400% of the initial lesion 24 h after impact [47].…”

Section: What Happens To the Acutely Traumatized Neural Tissue?mentioning

confidence: 99%

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Meirelles

Simon

Regner

2017

IJMS

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a major cause of morbidity and mortality among young individuals worldwide. Understanding the pathophysiology of neurotrauma is crucial for the development of more effective therapeutic strategies. After the trauma occurs, immediate neurologic damage is produced by the traumatic forces; this primary injury triggers a secondary wave of biochemical cascades together with metabolic and cellular changes, called secondary neural injury. In the scenario of the acutely injured brain, the ongoing secondary injury results in ischemia and edema culminating in an uncontrollable increase in intracranial pressure. These areas of secondary injury progression, or areas of “traumatic penumbra”, represent crucial targets for therapeutic interventions. Neurotrophins are a class of signaling molecules that promote survival and/or maintenance of neurons. They also stimulate axonal growth, synaptic plasticity, and neurotransmitter synthesis and release. Therefore, this review focuses on the role of neurotrophins in the acute post-injury response. Here, we discuss possible endogenous neuroprotective mechanisms of neurotrophins in the prevailing environment surrounding the injured areas, and highlight the crosstalk between neurotrophins and inflammation with focus on neurovascular unit cells, particularly pericytes. The perspective is that neurotrophins may represent promising targets for research on neuroprotective and neurorestorative processes in the short-term following TBI.

show abstract

Section: What Happens To the Acutely Traumatized Neural Tissue?mentioning

confidence: 99%

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Meirelles

Simon

Regner

2017

IJMS

View full text Add to dashboard Cite

show abstract

“…In regards to neurodegenerative disorders (29, 30), 800,000 strokes occur per year in the United States (US) at an annual cost of 75 billion US dollars (29). Traumatic brain injury (TBI) (31, 32) can have multiple effects resulting in acute injury to the nervous system as well as subsequent chronic aging-related impairment (33–35). Approximately 50,000 individuals die every year as a result of TBI and more than 100,000 individuals suffer with chronic disability (36).…”

Section: Increased Lifespan Degenerative Disorders and Cell Injurymentioning

confidence: 99%

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

Maiese¹

2016

CNR

View full text Add to dashboard Cite

Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. Yet, the biological and clinical outcome of these pathways can be complex especially with oversight of cell death mechanisms that involve apoptosis and autophagy. Growth factors, and in particular erythropoietin (EPO), are one avenue under consideration to implement control over cell death pathways since EPO can offer potential treatment for multiple disease entities and is intimately dependent upon mTOR signaling. In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies.

show abstract

“…As noted, trauma also significantly contributes to death and disability throughout the world and in particular, traumatic brain injury (TBI) can lead to devastating neurological disability [13,14]. TBI can result in impairments in memory and cognition, altered states of consciousness, psychiatric disturbances, and physical impairments that may be temporary or progress to permanent disability or death [15,16]. The combined rates for TBI related emergency department visits, hospitalizations, and deaths have significantly increased over the last ten years from 521 per 100,000 in 2001 to 824 per 100,000 in 2010 [17].…”

Section: Erythropoietin and Traumatic Brain Injury: Translating Expermentioning

confidence: 99%

Charting a course for erythropoietin in traumatic brain injury

Maiese¹

2016

J Transl Sci

View full text Add to dashboard Cite

Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. EPO can control cell death pathways tied to apoptosis and autophagy as well oversees processes that affect cellular longevity and aging. In vitro studies and experimental animal models of TBI have shown that EPO can restore axonal integrity, promote cellular proliferation, reduce brain edema, and preserve cellular energy homeostasis and mitochondrial function. Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI. KeywordsAkt; Alzheimer's disease; apoptosis; autophagy; erythropoietin; forkhead; mTOR; Parkinson's disease; neurodegeneration; programmed cell death; sirtuins; traumatic brain injury; Wnt Erythropoietin and traumatic brain injury: Translating experimental success into clinical efficacyIn more than 30 million individuals throughout the world, both acute and chronic neurodegenerative disorders can result in significant disability as well as eventual death [1,2]. Chronic neurodegenerative diseases, such as Parkinson's disease (PD) [3,4], can affect approximately 4 percent of individuals over the age of sixty. In addition, the number ofThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For the sporadic form of AD, approximately 10 percent of the global population over the age of sixty-five is affected [3,5]. Over the next two decades, it is estimated that the number of those suffering from AD will increase significantly to more than 30 million individuals [6][7][8]. HHS Public AccessFor acute neurodegenerative injury, disorders such as stroke can impact almost 800,000 individuals every year with a...

show abstract

Characterization of traumatic brain injury in human brains reveals distinct cellular and molecular changes in contusion and pericontusion

Cited by 83 publications

References 85 publications

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Neurotrauma: The Crosstalk between Neurotrophins and Inflammation in the Acutely Injured Brain

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

Charting a course for erythropoietin in traumatic brain injury

Contact Info

Product

Resources

About