Temporal Dynamics of Cerebral Blood Flow, Cortical Damage, Apoptosis, Astrocyteâ€“Vasculature Interaction and Astrogliosis in the Pericontusional Region after Traumatic Brain Injury

Villapol, Sonia; Byrnes, Kimberly R.; Symes, Aviva J.

doi:10.3389/fneur.2014.00082

Cited by 105 publications

(112 citation statements)

References 47 publications

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“…22,23 We found partial or complete damage of many small blood vessels in the hippocampal region after 3 hours of the injury ( Figure 3A). On average, one-third of the small blood vessels displayed varying degrees of damage, whereas no such damaged vessels were found in the control hippocampus ( Figure 3A).…”

Section: Low-level Light Suppresses Apoptosis Induced By Hypoxiamentioning

confidence: 93%

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Dong

Zhang

Hamblin

et al. 2015

J Cereb Blood Flow Metab

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Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energyproducing insufficient tissue-like injured brain.

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Section: Low-level Light Suppresses Apoptosis Induced By Hypoxiamentioning

confidence: 93%

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Dong

Zhang

Hamblin

et al. 2015

J Cereb Blood Flow Metab

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“…1B). Such focal lesions can vary considerably in size, and can encompass large areas or can be restricted to small clusters of cells (Myer et al, 2006; Villapol et al, 2014). …”

Section: Multiple Forms and Severities Of Tbi And Tissue Damagementioning

confidence: 99%

Astrocyte roles in traumatic brain injury

Burda

Bernstein

Sofroniew

2016

Experimental Neurology

612

510

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Astrocytes sense changes in neural activity and extracellular space composition. In response, they exert homeostatic mechanisms critical for maintaining neural circuit function, such as buffering neurotransmitters, modulating extracellular osmolarity and calibrating neurovascular coupling. In addition to upholding normal brain activities, astrocytes respond to diverse forms of brain injury with heterogeneous and progressive changes of gene expression, morphology, proliferative capacity and function that are collectively referred to as reactive astrogliosis. Traumatic brain injury (TBI) sets in motion complex events in which noxious mechanical forces cause tissue damage and disrupt central nervous system (CNS) homeostasis, which in turn trigger diverse multi-cellular responses that evolve over time and can lead either to neural repair or secondary cellular injury. In response to TBI, astrocytes in different cellular microenvironments tune their reactivity to varying degrees of axonal injury, vascular disruption, ischemia and inflammation. Here we review different forms of TBI-induced astrocyte reactivity and the functional consequences of these responses for TBI pathobiology. Evidence regarding astrocyte contribution to post-traumatic tissue repair and synaptic remodeling is examined, and the potential for targeting specific aspects of astrogliosis to ameliorate TBI sequelae is considered.

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“…43,44 In the pericontusional tissue, some researchers differentiate between penumbra, parapenumbra, and normal brain with the goal of separating the molecular mechanism involved in each zone. 4,8 Pericontusional tissue absorbs part of the kinetic energy delivered at the time of injury, activating mechanoreceptors and downstream molecular pathways.…”

Section: Discussionmentioning

confidence: 99%

Sulfonylurea Receptor 1 in Humans with Post-Traumatic Brain Contusions

Martínez-Valverde

Vidal-Jorge

Martínez‐Sáez

et al. 2015

Journal of Neurotrauma

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Post-traumatic brain contusions (PTBCs) are traditionally considered primary injuries and can increase in size, generate perilesional edema, cause mass effect, induce neurological deterioration, and cause death. Most patients experience a progressive increase in pericontusional edema, and nearly half, an increase in the hemorrhagic component itself. The underlying molecular pathophysiology of contusion-induced brain edema and hemorrhagic progression remains poorly understood. The aim of this study was to investigate sulfonylurea 1/transient receptor potential melastatin 4 (SUR1-TRPM4) ion channel SUR1 expression in various cell types (neurons, astrocytes, endothelial cells, microglia, macrophages, and neutrophils) of human brain contusions and whether SUR1 up-regulation was related to time postinjury. Double immunolabeling of SUR1 and cell-type-specific proteins was performed in 26 specimens from traumatic brain injury patients whose lesions were surgically evacuated. Three samples from limited brain resections performed for accessing extra-axial skull-base tumors or intraventricular lesions were controls. We found SUR1 was significantly overexpresed in all cell types and was especially prominent in neurons and endothelial cells (ECs). The temporal pattern depended on cell type: 1) In neurons, SUR1 increased within 48 h of injury and stabilized thereafter; 2) in ECs, there was no trend; 3) in glial cells and microglia/macrophages, a moderate increase was observed over time; and 4) in neutrophils, it decreased with time. Our results suggest that up-regulation of SUR1 in humans point to this channel as one of the important molecular players in the pathophysiology of PTBCs. Our findings reveal opportunities to act therapeutically on the mechanisms of growth of traumatic contusions and therefore reduce the number of patients with neurological deterioration and poor neurological outcomes.

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Temporal Dynamics of Cerebral Blood Flow, Cortical Damage, Apoptosis, Astrocyteâ€“Vasculature Interaction and Astrogliosis in the Pericontusional Region after Traumatic Brain Injury

Cited by 105 publications

References 47 publications

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Low-Level Light in Combination with Metabolic Modulators for Effective Therapy of Injured Brain

Astrocyte roles in traumatic brain injury

Sulfonylurea Receptor 1 in Humans with Post-Traumatic Brain Contusions

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