Traumatic brain injury‐induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis

Rao, Venkat K.; Dhodda, Vinay K.; Song, Guo-Qing; Bowen, Kellie K.; Dempsey, Robert J.

doi:10.1002/jnr.10486

Cited by 126 publications

(47 citation statements)

References 80 publications

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“…Previous array expression studies in TBI models have demonstrated that the brain mounts a specific and concerted genomic response to injury, specifically upregulating certain genes and suppressing others ( Matzilevich et al, 2002;Raghavendra et al, 2003). Because the brain is a complex multicellular organ composed of a variety of cell types that exhibit potentially divergent genomic responses to injury, analyses of whole regions or subregions of the brain will confound the specific contributions from individual neurons.…”

Section: Discussionmentioning

confidence: 99%

Neuron-Specific mRNA Complexity Responses during Hippocampal Apoptosis after Traumatic Brain Injury

Marciano¹,

Brettschneider²,

Manduchi³

et al. 2004

J. Neurosci.

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In an effort to understand the complexity of genomic responses within selectively vulnerable regions after experimental brain injury, we examined whether single apoptotic neurons from both the CA3 and dentate differed from those in an uninjured brain. The mRNA from individual active caspase 3(ϩ)/terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling [TUNEL(Ϫ)] and active caspase 3(ϩ)/TUNEL(ϩ) pyramidal and granule neurons in brain-injured mice were amplified and compared with those from nonlabeled neurons in uninjured brains. Gene analysis revealed that overall expression of mRNAs increased with activation of caspase 3 and decreased to below uninjured levels with TUNEL reactivity. Cell type specificity of the apoptotic response was observed with both regionally distinct expression of mRNAs and differences in those mRNAs that were maximally regulated. Immunohistochemical analysis for two of the most highly differentially expressed genes ( prion and Sos2) demonstrated a correlation between the observed differential gene expression after traumatic brain injury and corresponding protein translation.

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Section: Discussionmentioning

confidence: 99%

Neuron-Specific mRNA Complexity Responses during Hippocampal Apoptosis after Traumatic Brain Injury

Marciano¹,

Brettschneider²,

Manduchi³

et al. 2004

J. Neurosci.

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“…This model reproduces many of the features of human brain injuries including motor deficits, memory loss, and neuron loss (Colicos et al, 1996). Responses following controlled cortical impact include glial activation, cytokine expression, and BBB disruption (Koshinaga et al, 2007; Raghavendra Rao et al, 2003) throughout the ipsilateral cortex and hippocampus (Smith et al, 1995). …”

Section: Introductionmentioning

confidence: 99%

Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice

Lee

Kim

Williams

et al. 2012

Experimental Neurology

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Aging alters the ability of the brain to respond to injury. One of the major differences between the adult and aged brain is that comparable injuries lead to greater blood brain barrier disruption in the aged brain. The goals of these studies were to quantify the effects of age on BBB permeability using high field strength MRI T1 mapping and to determine whether activation of matrix metalloproteases, their inhibitors, or expression of blood brain barrier structural proteins, occludin, zonnula occludins-1 (ZO-1) and claudin-5 were altered following injury to the aged C57/Bl6 mouse brain. T1 mapping studies revealed greater blood brain barrier permeability in the aged (21–15 months old) brain than in the adult (4–6 months old) following controlled cortical impact. The increased blood brain barrier permeability in the pericontusional region was confirmed with IgG immunohistochemistry. MMP-9 activity was increased following controlled cortical impact in the aged brain, and this was accompanied by increased MMP-9 gene expression. MMP-2 activity was higher in the uninjured aged brain than in the adult brain. Occludin and ZO-1 mRNA levels were unchanged following injury in either age group, but claudin-5 mRNA levels were lower in the aged than the adult brain following injury. These results demonstrate quantitative increases in blood brain barrier permeability in the aged brain following injury that are accompanied by increased MMP-9 activation and decreased blood brain barrier repair responses.

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“…Because SOCS-3 may also be neuroprotective as SOCS-3 and other members of SOCS family increase after focal stroke, cerebral ischemia, traumatic brain injury, and spinal chord injury (7,43) and antisense knockdown of SOCS-3 expression increases stroke size (43), we explored the role of SOCS-3 in cell survival, in response to TNF␣ and IGF-1. An 80% decrease in cell survival was observed in SOCS-3-transfected cells following IGF-1 stimulation, as compared with 20% (statistically insignificant) in the case of TNF␣ (Fig.…”

Section: Socs-3 Inhibits Cell Growth Inmentioning

confidence: 99%

JAK/STAT3 Pathway Is Involved in Survival of Neurons in Response to Insulin-like Growth Factor and Negatively Regulated by Suppressor of Cytokine Signaling-3

Yadav

Kalita

Dhillon

et al. 2005

Journal of Biological Chemistry

125

126

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Janus kinases (JAK) and signal transducers and activator of transcription (STAT) proteins are activated in response to many cytokines and growth factors and are well studied in the immune system. This study was conducted to examine the role of the JAK/STAT pathway in neurons in response to tumor necrosis factor-␣ (TNF␣) and insulin-like growth factor-1 (IGF-1), which play a major role during neurodegeneration, and to study their effect on expression of suppressors of cytokine signaling 3 (SOCS-3), belonging to the novel family of feedback regulators of cytokine and growth factor activities. In this report, we showed that TNF␣ is inhibitory to the survival of primary cortical neurons at higher doses and that IGF-1 can rescue TNF␣-stimulated cell death. We showed that the JAK/ STAT pathway is involved in this rescue as tyrphostin AG490, a specific inhibitor of JAK/STAT, completely inhibits cell survival in response to IGF-1. STAT3 gets tyrosine-phosphorylated and translocated to the nucleus in response to IGF-1. Northern blot, semi-quantitative reverse transcription-PCR, and real time PCR experiments demonstrated that the JAK/STAT pathway also up-regulated SOCS-3 mainly in response to IGF-1. SOCS-3 associated with the IGF receptor and blocked further STAT3 activation. To our knowledge, this is the first report that demonstrated the importance of the JAK/STAT pathway and the role of SOCS-3 in the survival of neurons in response to IGF-1. We have subsequently shown that SOCS-3 overexpression, on one hand, leads to neuroblastoma cell death and on the other hand leads to primary cell differentiation, indicating the involvement of SOCS-3 in cell survival and differentiation.

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Traumatic brain injury‐induced acute gene expression changes in rat cerebral cortex identified by GeneChip analysis

Cited by 126 publications

References 80 publications

Neuron-Specific mRNA Complexity Responses during Hippocampal Apoptosis after Traumatic Brain Injury

Neuron-Specific mRNA Complexity Responses during Hippocampal Apoptosis after Traumatic Brain Injury

Effects of aging on blood brain barrier and matrix metalloproteases following controlled cortical impact in mice

JAK/STAT3 Pathway Is Involved in Survival of Neurons in Response to Insulin-like Growth Factor and Negatively Regulated by Suppressor of Cytokine Signaling-3

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