Linking impact to cellular and molecular sequelae of CNS injury: Modeling in vivo complexity with in vitro simplicity

Spaethling, Jennifer M.; Geddes-Klein, Donna M.; Miller, William J.; Reyn, Catherine R. von; Singh, Pallab; Mesfin, Mahlet N.; Bernstein, Steven J.; Meaney, David F.

doi:10.1016/s0079-6123(06)61003-0

Cited by 26 publications

(21 citation statements)

References 114 publications

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“…With the clear need for coupling mechanical input into functional consequences, work in the past decade has responded and provided more direct insight into the mechanisms that cause the resulting functional changes. Motivated by the early work using physical models and finite element simulations, several investigators developed microscope-based systems to study directly the relationship between the mechanical deformation and resultant biochemical signaling [183][184][185][186][187][188][189]. As a result, we now know that both neural and glial cells respond to mechanical deformation, that synaptically localized receptors are uniquely mechanosensitive, show immediate alterations in their physiological properties, and changes occur across both excitatory and inhibitory neurons [190][191][192][193][194][195].…”

Section: Linking the Physical Response To The Biological Responsementioning

confidence: 99%

The Mechanics of Traumatic Brain Injury: A Review of What We Know and What We Need to Know for Reducing Its Societal Burden

Meaney

Morrison

Bass

2014

Journal of Biomechanical Engineering

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212

126

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Traumatic brain injury (TBI) is a significant public health problem, on pace to become the third leading cause of death worldwide by 2020. Moreover, emerging evidence linking repeated mild traumatic brain injury to long-term neurodegenerative disorders points out that TBI can be both an acute disorder and a chronic disease. We are at an important transition point in our understanding of TBI, as past work has generated significant advances in better protecting us against some forms of moderate and severe TBI. However, we still lack a clear understanding of how to study milder forms of injury, such as concussion, or new forms of TBI that can occur from primary blast loading. In this review, we highlight the major advances made in understanding the biomechanical basis of TBI. We point out opportunities to generate significant new advances in our understanding of TBI biomechanics, especially as it appears across the molecular, cellular, and whole organ scale.

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Section: Linking the Physical Response To The Biological Responsementioning

confidence: 99%

The Mechanics of Traumatic Brain Injury: A Review of What We Know and What We Need to Know for Reducing Its Societal Burden

Meaney

Morrison

Bass

2014

Journal of Biomechanical Engineering

Self Cite

212

126

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“…A complex cascade of processes is activated and generates continued endogenous changes affecting cellular systems and the overall outcome from the initial insult to the brain (1). Homeostatic cellular processes governing synaptic neurotransmission, cytoskeletal structure, redox balance, calcium influx, and mitochondrial function often become dysfunctional after TBI.…”

Section: Tbimentioning

confidence: 99%

“…The Lipidomics Core Facility at Medical University of South Carolina is supported in part by National Institutes of Health Grant P30 GM103339. 1 apoptosis (9). The building block of many complex sphingolipids is ceramide, which has numerous cellular signaling functions and plays a key role in promoting apoptosis (10,11).…”

Section: Tbimentioning

confidence: 99%

Essential Roles of Neutral Ceramidase and Sphingosine in Mitochondrial Dysfunction Due to Traumatic Brain Injury

Novgorodov

Riley

et al. 2014

Journal of Biological Chemistry

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Background: A cardinal feature of many neurological disorders is mitochondrial dysfunction. Results: Knocking down neutral ceramidase reduces mitochondrial sphingosine, preserves mitochondrial function, and improves brain function recovery after trauma. Conclusion: Activation of the sphingosine-generating pathway plays a significant role in promoting mitochondrial injury. Significance: This is the first direct evidence of endogenous sphingosine involvement in regulation of mitochondrial function.

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“…The central nervous system (CNS; i.e. the brain and spinal cord) is a particularly challenging tissue system in this regard, due to the complex cellular dynamics and intricate (cardinal) pathophysiological events displayed after neurological injury [13]. For example, following SCI in vivo: astrocytes upregulate expression of the astrocyte-specific marker glial fibrillary acidic protein (GFAP), within and adjacent to lesions, to form a scar that constitutes a critical barrier to axonal regeneration [14]; microglia (the immune-competent cells of the CNS) infiltrate into lesion sites and are responsible for the breakdown and phagocytosis of cellular debris and toxic substances following injury [15,16]; and limited, spontaneous sprouting of nerve fibers occurs from lesion margins, with the extent of regeneration declining with age [17].…”

Section: Introductionmentioning

confidence: 99%

An in vitro spinal cord injury model to screen neuroregenerative materials

Weightman¹,

Pickard²,

Yang³

et al. 2014

Biomaterials

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Implantable 'structural bridges' based on nanofabricated polymer scaffolds have great promise to aid spinal cord regeneration. Their development (optimal formulations, surface functionalizations, biocompatibility, topographical influences and degradation profiles) is heavily reliant on live animal injury models. These have several disadvantages including invasive surgical procedures, ethical issues, high animal usage, technical complexity and expense. In vitro 3-D organotypic slice arrays could offer a novel solution to overcome these challenges, but their utility for nanomaterials testing is undetermined. We have developed an in vitro model of spinal cord injury that replicates stereotypical cellular responses to neurological injury in vivo, viz. reactive gliosis, microglial infiltration and limited nerve fibre outgrowth. We describe a facile method to safely incorporate aligned, poly-lactic acid nanofiber meshes (± poly-lysine + laminin coating) within injury sites using a lightweight

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Linking impact to cellular and molecular sequelae of CNS injury: Modeling in vivo complexity with in vitro simplicity

Cited by 26 publications

References 114 publications

The Mechanics of Traumatic Brain Injury: A Review of What We Know and What We Need to Know for Reducing Its Societal Burden

The Mechanics of Traumatic Brain Injury: A Review of What We Know and What We Need to Know for Reducing Its Societal Burden

Essential Roles of Neutral Ceramidase and Sphingosine in Mitochondrial Dysfunction Due to Traumatic Brain Injury

An in vitro spinal cord injury model to screen neuroregenerative materials

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