Increased expression of brain-derived neurotrophic factor but not neurotrophin-3 mRNA in rat brain after cortical impact injury

Yang, Kuo-Hsin; Perez‐Polo, J. Regino; Mu, X. S.; Yan, Hong; Xue, Jian-Fu; Iwamoto, Yoshihiro; Liu, S.J.; Dixon, C. Edward; Hayes, Ronald L.

doi:10.1002/(sici)1097-4547(19960415)44:2<157::aid-jnr8>3.0.co;2-c

Cited by 92 publications

(48 citation statements)

References 52 publications

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“…Classically in neurons, PKA phosphorylates the transcription factor CREB to increase expression of cell survival genes such as BDNF and the anti-apoptotic protein bcl-2 (Freeland et al, 2001, Tabuchi et al, 2002, Deogracias et al, 2004, Meller et al, 2005. Previous studies have reported that CREB is activated after TBI and BDNF levels are elevated as well (Dash et al, 1995, Yang et al, 1996, Hicks et al, 1997, Truettner et al, 1999, Griesbach et al, 2004a, Griesbach et al, 2004b, Hu et al, 2004. Multiple protein kinases can phosphorylate CREB; a few of these include calcium/calmodulindependent protein kinase IV, ribosomal protein S6 kinase, mitogen-and stress-activated protein kinase, and MAP kinase-activated protein kinase-2 (Sun et al, 1994, Tan et al, 1996, Xing et al, 1996, Deak et al, 1998, Shaywitz and Greenberg, 1999, Bito and Takemoto-Kimura, 2003.…”

Section: Discussionmentioning

confidence: 99%

Modulation of the cAMP signaling pathway after traumatic brain injury

Atkins

Oliva

Alonso

et al. 2007

Experimental Neurology

137

151

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Traumatic brain injury (TBI) results in both focal and diffuse brain pathologies that are exacerbated by the inflammatory response and progress from hours to days after the initial injury. Using a clinically relevant model of TBI, the parasagittal fluid-percussion brain injury (FPI) model, we found injury-induced impairments in the cyclic AMP (cAMP) signaling pathway. Levels of cAMP were depressed in the ipsilateral parietal cortex and hippocampus, as well as activation of its downstream target, protein kinase A, from 15 min to 48 hr after moderate FPI. To determine if preventing hydrolysis of cAMP by administration of a phosphodiesterase (PDE) IV inhibitor would improve outcome after TBI, we treated animals intraperitoneally with rolipram (0.3 or 3.0 mg/kg) 30 min prior to TBI, and then once per day for three days. Rolipram treatment restored cAMP to sham levels and significantly reduced cortical contusion volume and improved neuronal cell survival in the parietal cortex and CA3 region of the hippocampus. Traumatic axonal injury, characterized by β-amyloid precursor protein deposits in the external capsule, was also significantly reduced in rolipramtreated animals. Furthermore, levels of the pro-inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), were significantly decreased with rolipram treatment. These results demonstrate that the cAMP-PKA signaling cascade is downregulated after TBI, and that treatment with a PDE IV inhibitor improves histopathological outcome and decreases inflammation after TBI. Keywordscamp; Fluid-percussion; Inflammation; Interleukin-1β; PKA; Phosphodiesterase; Rolipram; TNF-α; Traumatic brain injury; TBI Traumatic brain injury (TBI) is a prevalent, debilitating health problem, occurring in 1.4 million people each year and disabling 5 million people in the United States (Langlois et al., 2004). The subsequent progressive injury after brain trauma develops from hours to days after the initiating insult, providing an accessible time window for pharmacological therapies. Despite Address correspondence to: W. Dalton Dietrich, Scientific Director, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, P.O. Box 016960, (R-48), Miami, FL 33101, E-mail: ddietrich@miami.edu, Phone: 305-243-2297, Fax: 305-243-3207. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Brain trauma results in contusion formation, neuronal apoptosis, and axonal tract damage. These pathologies are worsened by the inflammatory cascade set into motion by the initial injury (Morganti-Kossmann et al., 2002. Two pro-i...

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Section: Discussionmentioning

confidence: 99%

Modulation of the cAMP signaling pathway after traumatic brain injury

Atkins

Oliva

Alonso

et al. 2007

Experimental Neurology

137

151

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“…Experimental TBI in rodents results in early increases in BDNF mRNA levels that persist for days in the cortex but are more transient in the hippocampus [103][104][105]. Although BDNF infusion into the cortex or hippocampus failed to improve outcome following TBI in rats [106], transplantation of BDNF-overexpressing neural stem cells into the cortex of brain-injured rats improved sensory motor function [107].…”

Section: Neurotrophins (Nt-4/5 Bdnf)mentioning

confidence: 99%

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

2012

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Traumatic brain injury (TBI) initiates a complex cascade of secondary neurodegenerative mechanisms contributing to cell dysfunction and necrotic and apoptotic cell death. The injured brain responds by activating endogenous reparative processes to counter the neurodegeneration or remodel the brain to enhance functional recovery. A vast array of genetically altered mice provide a unique opportunity to target single genes or proteins to better understand their role in cell death and endogenous repair after TBI. Among the earliest targets for transgenic and knockout studies in TBI have been programmed cell death mediators, such as the Bcl-2 family of proteins, caspases, and caspaseindependent pathways. In addition, the role of cell cycle regulatory elements in the posttraumatic cell death pathway has been explored in mouse models. As interest grows in neuroplasticity in TBI, the use of transgenic and knockout mice in studies focused on gliogenesis, neurogenesis, and the balance of growth-promoting and growth-inhibiting molecules has increased in recent years. With proper consideration of potential effects of constitutive gene alteration, traditional transgenic and knockout models can provide valuable insights into TBI pathobiology. Through increasing sophistication of conditional and cell-type specific genetic manipulations, TBI studies in genetically altered mice will be increasingly useful for identification and validation of novel therapeutic targets.

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“…Some neurotrophic factors such as NGF and BDNF are up-regulated, while others such as neurotrophic factor-3 (NT-3) have been shown to be down-regulated (Yang, et al, 1996, Hicks, et al, 1997, Oyesiku, et al, 1999, Truettner, et al, 1999. Interestingly, BDNF levels after TBI have been reported to be increased to a greater extent in older rather than younger animals (Shah, et al, 2006), despite the well known fact that older age is correlated with a worse outcome after TBI.…”

Section: Potential Mechanisms Of Increased Neurogenesis After Tbimentioning

confidence: 99%

Compensatory Neurogenesis in the Injured Adult Brain

Connor¹

2012

Brain Injury - Pathogenesis, Monitoring, Recovery and Management

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Increased expression of brain-derived neurotrophic factor but not neurotrophin-3 mRNA in rat brain after cortical impact injury

Cited by 92 publications

References 52 publications

Modulation of the cAMP signaling pathway after traumatic brain injury

Modulation of the cAMP signaling pathway after traumatic brain injury

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

Compensatory Neurogenesis in the Injured Adult Brain

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