Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature

Schouten, Joost W.

doi:10.1097/mcc.0b013e3280895d5c

Cited by 131 publications

(91 citation statements)

References 65 publications

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“…The etiology of secondary brain injury is multi-factorial, with a host of likely inter-related processes including mitochondrial energy failure; excessive generation of reactive oxygen species; activation of destructive enzymes such as poly (ADP-ribose) polymerase (PARP), and the caspase family of proteases; membrane disruption; neuronal death; thrombosis caused by intravascular coagulation in small vessels; increased synaptic concentrations of excitatory amino acids; and activation of innate inflammatory responses (Schouten, 2007). Several reviews have suggested the need for pharmacological treatments that target multiple secondary factors, or combination treatment strategies (Faden and Stoica, 2007;Schouten, 2007).…”

Section: T He Centers For Disease Control and Preventionmentioning

confidence: 99%

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The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

Anderson

Farin

Bammler

et al. 2011

Journal of Neurotrauma

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Microarray-based transcriptional profiling was used to determine the effect of progesterone in the cortical contusion (CCI) model. Gene ontology (GO) analysis then evaluated the effect of dose on relevant biological pathways. Treatment (vehicle, progesterone 10 mg/kg or 20 mg/kg given i.p.) was started 4 h post-injury and administered every 12 h post-injury for up to 72 h, with the last injection 12 hr prior to death for the 24 h and 72 h groups. In the CCI-injured vehicle group compared to non-injured animals, expression of 1,114, 4,229, and 291 distinct genes changed > 1.5-fold ( p < 0.05) at 24 h, 72 h, and 7 days, respectively. At 24 h, the effect of low-dose progesterone on differentially expressed genes was < 20% the effect of higher dose compared to vehicle. GO analysis identified a significant effect of low-and high-dose progesterone treatment compared to vehicle on DNA damage response. At 72 h, high-dose progesterone treatment compared to vehicle affected expression of almost twice as many genes as did low-dose progesterone. Both low-and high-dose progesterone resulted in expression of genes regulating inflammatory response and apoptosis. At 7 days, there was only a modest difference in high-dose progesterone compared to vehicle, with only 14 differentially expressed genes. In contrast, low-dose progesterone resulted in 551 differentially expressed genes compared to vehicle. GO analysis identified genes for the low-dose treatment involved in positive regulation of cell proliferation, innate immune response, positive regulation of anti-apoptosis, and blood vessel remodeling.

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Section: T He Centers For Disease Control and Preventionmentioning

confidence: 99%

“…Several reviews have suggested the need for pharmacological treatments that target multiple secondary factors, or combination treatment strategies (Faden and Stoica, 2007;Schouten, 2007).…”

Section: T He Centers For Disease Control and Preventionmentioning

confidence: 99%

The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

Anderson

Farin

Bammler

et al. 2011

Journal of Neurotrauma

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“…La neuroprotección intenta bloquear las cascadas fisiopatológicas que desembocan en el daño cerebral secundario, así como contribuir a la reparación del sistema nervioso central 17 .…”

Section: Neuroprotecciónunclassified

Actualizaciones en el manejo del traumatismo craneoencefálico grave

2009

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El traumatismo craneoencefálico (TCE) es una importante causa de morbimortalidad en cualquier lugar del mundo; afecta más a varones jóvenes y genera un problema de salud pública. Desafortunadamente, los avances en los conocimientos fisiopatológicos no han ido seguidos de similar desarrollo en las opciones terapéuticas, y no se dispone en la actualidad de fármacos neuroprotectores contrastados.En este artículo revisamos la epidemiología, la fisiopatología y las medidas terapéuticas utilizadas en el manejo del paciente con TCE grave. Se analizan tanto las medidas generales como las dirigidas al control de la hipertensión intracraneal, el papel de la cirugía y algunas opciones terapéu-ticas más innovadoras actualmente en fase de valoración en estos pacientes. UPDATES OF SEVERE TRAUMATIC BRAIN INJURY MANAGEMENT Traumatic brain injury (TBI)is an important reason of morbidity-mortality all over the world, affecting young males more and generating Public Health problem. Unfortunately, the advances in the pathophysiology knowledge have not followed a similar development in therapeutic options, there currently not being any contrasted neuroprotectants.In this article, we have reviewed the epidemiology, pathophysiology and therapeutic measures used in the management of patient with severe TBI. The general measures as well as those aimed at controlling intracranial hypertension, the role of the surgery and some more innovative therapeutic options currently under evaluation in these patients are analyzed.

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“…The resulting complex gene expression profiles obtained from these heterogeneous tissues, and the often conflicting patterns of injury-induced cellular signals, may be one explanation for the failure in human clinical trials of therapeutic strategies proven effective in pre-clinical studies of TBI. 5 To obtain a clear understanding of injury-induced gene expression in vulnerable populations of neurons from the rat hippocampus, we adopted the technique of LCM, first reported by Emmert-Buck et al 3 Subsequently, we modified and optimized this microdissection technique for efficient capture of enriched populations of neurons and single neurons for mRNA profiling using quantitative real time PCR and microarray analysis. To maintain the integrity of mRNA in frozen sections of brain tissue for genomic analysis, we modified existing protocols for fixing, staining and rapid capture of neurons from frozen rat brain sections.…”

Section: Introductionmentioning

confidence: 99%

Laser Capture Microdissection of Enriched Populations of Neurons or Single Neurons for Gene Expression Analysis After Traumatic Brain Injury

Boone

Sell

Hellmich

2013

JoVE

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Long-term cognitive disability after TBI is associated with injury-induced neurodegeneration in the hippocampus-a region in the medial temporal lobe that is critical for learning, memory and executive function.1,2 Hence our studies focus on gene expression analysis of specific neuronal populations in distinct subregions of the hippocampus. The technique of laser capture microdissection (LCM), introduced in 1996 by et al.,3 has allowed for significant advances in gene expression analysis of single cells and enriched populations of cells from heterogeneous tissues such as the mammalian brain that contains thousands of functional cell types. 4 We use LCM and a well established rat model of traumatic brain injury (TBI) to investigate the molecular mechanisms that underlie the pathogenesis of TBI. Following fluidpercussion TBI, brains are removed at pre-determined times post-injury, immediately frozen on dry ice, and prepared for sectioning in a cryostat. The rat brains can be embedded in OCT and sectioned immediately, or stored several months at -80 °C before sectioning for laser capture microdissection. Additionally, we use LCM to study the effects of TBI on circadian rhythms. For this, we capture neurons from the suprachiasmatic nuclei that contain the master clock of the mammalian brain. Here, we demonstrate the use of LCM to obtain single identified neurons (injured and degenerating, Fluoro-Jade-positive, or uninjured, Fluoro-Jade-negative) and enriched populations of hippocampal neurons for subsequent gene expression analysis by real time PCR and/or whole-genome microarrays. These LCM-enabled studies have revealed that the selective vulnerability of anatomically distinct regions of the rat hippocampus are reflected in the different gene expression profiles of different populations of neurons obtained by LCM from these distinct regions. The results from our single-cell studies, where we compare the transcriptional profiles of dying and adjacent surviving hippocampal neurons, suggest the existence of a cell survival rheostat that regulates cell death and survival after TBI.

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Neuroprotection in traumatic brain injury: a complex struggle against the biology of nature

Cited by 131 publications

References 65 publications

The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

The Effect of Progesterone Dose on Gene Expression after Traumatic Brain Injury

Actualizaciones en el manejo del traumatismo craneoencefálico grave

Laser Capture Microdissection of Enriched Populations of Neurons or Single Neurons for Gene Expression Analysis After Traumatic Brain Injury

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