1
40
1
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1186/1742-2094-5-28" target="_blank" rel="noreferrer noopener">http://doi.org/10.1186/1742-2094-5-28</a>
Pages
28–28
Volume
5
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
A name given to the resource
Suppression of acute proinflammatory cytokine and chemokine upregulation by post-injury administration of a novel small molecule improves long-term neurologic outcome in a mouse model of traumatic brain injury.
Publisher
An entity responsible for making the resource available
Journal of neuroinflammation
Date
A point or period of time associated with an event in the lifecycle of the resource
2008
2008-06
Subject
The topic of the resource
Animal; Animals; Brain Injuries/blood/epidemiology/genetics/*physiopathology; Cerebral Cortex/physiopathology; Chemokine CCL2/genetics/physiology; Chemokines/*genetics; Cytokines/*antagonists & inhibitors; Disease Models; Hippocampus/physiopathology; Inflammation/genetics/*physiopathology; Interleukin-1beta/genetics/physiology; Interleukin-6/genetics/physiology; Male; Mice; Tumor Necrosis Factor-alpha/genetics/physiology; United States/epidemiology; Up-Regulation
Creator
An entity primarily responsible for making the resource
Lloyd Eric; Somera-Molina Kathleen; Van Eldik Linda J; Watterson D Martin; Wainwright Mark S
Description
An account of the resource
BACKGROUND: Traumatic brain injury (TBI) with its associated morbidity is a major area of unmet medical need that lacks effective therapies. TBI initiates a neuroinflammatory cascade characterized by activation of astrocytes and microglia, and increased production of immune mediators including proinflammatory cytokines and chemokines. This inflammatory response contributes both to the acute pathologic processes following TBI including cerebral edema, in addition to longer-term neuronal damage and cognitive impairment. However, activated glia also play a neuroprotective and reparative role in recovery from injury. Thus, potential therapeutic strategies targeting the neuroinflammatory cascade must use careful dosing considerations, such as amount of drug and timing of administration post injury, in order not to interfere with the reparative contribution of activated glia. METHODS: We tested the hypothesis that attenuation of the acute increase in proinflammatory cytokines and chemokines following TBI would decrease neurologic injury and improve functional neurologic outcome. We used the small molecule experimental therapeutic, Minozac (Mzc), to suppress TBI-induced up-regulation of glial activation and proinflammatory cytokines back towards basal levels. Mzc was administered in a clinically relevant time window post-injury in a murine closed-skull, cortical impact model of TBI. Mzc effects on the acute increase in brain cytokine and chemokine levels were measured as well as the effect on neuronal injury and neurobehavioral function. RESULTS: Administration of Mzc (5 mg/kg) at 3 h and 9 h post-TBI attenuates the acute increase in proinflammatory cytokine and chemokine levels, reduces astrocyte activation, and the longer term neurologic injury, and neurobehavioral deficits measured by Y maze performance over a 28-day recovery period. Mzc-treated animals also have no significant increase in brain water content (edema), a major cause of the neurologic morbidity associated with TBI. CONCLUSION: These results support the hypothesis that proinflammatory cytokines contribute to a glial activation cycle that produces neuronal dysfunction or injury following TBI. The improvement in long-term functional neurologic outcome following suppression of cytokine upregulation in a clinically relevant therapeutic window indicates that selective targeting of neuroinflammation may lead to novel therapies for the major neurologic morbidities resulting from head injury, and indicates the potential of Mzc as a future therapeutic for TBI.
Identifier
An unambiguous reference to the resource within a given context
<a href="http://doi.org/10.1186/1742-2094-5-28" target="_blank" rel="noreferrer noopener">10.1186/1742-2094-5-28</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2008
Animal
Animals
Brain Injuries/blood/epidemiology/genetics/*physiopathology
Cerebral Cortex/physiopathology
Chemokine CCL2/genetics/physiology
Chemokines/*genetics
Cytokines/*antagonists & inhibitors
Disease Models
Hippocampus/physiopathology
Inflammation/genetics/*physiopathology
Interleukin-1beta/genetics/physiology
Interleukin-6/genetics/physiology
Journal of neuroinflammation
Lloyd Eric
Male
Mice
Somera-Molina Kathleen
Tumor Necrosis Factor-alpha/genetics/physiology
United States/epidemiology
Up-Regulation
Van Eldik Linda J
Wainwright Mark S
Watterson D Martin