Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Li, Yonggang; Xu, Zhen; Ford, Gregory D.; Croslan, DaJoie R.; Cairobe, Tariq; Li, Zhenzhong; Ford, Byron D.

doi:10.1016/j.brainres.2007.09.037

Cited by 76 publications

(67 citation statements)

References 41 publications

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“…NRG-induced ErbB signaling plays an important role in the development and homeostasis of the nervous system (2,23,24), and may even be a candidate for neuroprotection (25,26). Its role in the developing lung is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Neuregulin Receptor ErbB4 Functions as a Transcriptional Cofactor for the Expression of Surfactant Protein B in the Fetal Lung

Zscheppang¹,

Dörk²,

Schmiedl

et al. 2011

Am J Respir Cell Mol Biol

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Sufficient pulmonary surfactant production is required for the fetalneonatal transition, especially in preterm infants. Neuregulin (NRG) and its transmembrane receptor ErbB4 positively regulate the onset of fetal surfactant synthesis. Details of this signaling process remain to be elucidated. ErbB4 is known to regulate gene expression in the mammary gland, where the receptor associates with the signal transducer and activator of transcription Stat5a to transactivate the b-casein gene promoter. We hypothesized that in the fetal lung, ErbB4 functions as a transcriptional regulator for surfactant protein B (Sftpb), the most critical surfactant protein gene. Re-expressing fulllength ErbB4 in primary fetal ErbB4-depleted Type II epithelial cells led to an increased expression of Sftpb mRNA. This stimulatory effect required the nuclear translocation of ErbB4 and association with Stat5a, with the resultant binding to and activation of the Sftpb promoter. We conclude that ErbB4 directly regulates important aspects of fetal lung maturation that help prepare for the fetalneonatal transition.Keywords: Surfactant; Type II cell; Stat5a; lung developmentThe differentiation of the neuronal (1, 2) and mammary (3) systems requires proper signaling between the growth factor neuregulin (NRG) and its cell-surface receptor, ErbB4. In the fetal lung, NRG is required for the initiation of fetal surfactant synthesis (4), and ErbB receptors (named because of their homology to the erythroblastoma viral gene product, v-erbB), also known as human epidermal growth factor receptors (HERs), are involved in the timely progression of fetal lung cell differentiation (4-6).Surface-active agents (surfactants) prevent pulmonary alveoli from collapsing at end-expiration. Therefore, the synthesis of surfactants by fetal pulmonary Type II cells is a crucial part of prenatal lung development (7), in preparation for the transition at birth from the intrauterine (aquatic) to the extrauterine (aerobic) environment. ErbB4, the signaling receptor for NRG, is the most prominent receptor dimerization partner in fetal Type II epithelial cells (8) and the down-regulation of ErbB4 inhibits fetal surfactant synthesis (9).Fetal ErbB4 transgenic mice that are rescued from their lethal heart defect by expressing human ErbB4 cDNA under the control of the cardiac-specific myosin heavy chain (a-HMC) promoter (HER4 heart ) (3) exhibit changes in lung function and structure, resulting in a hyperreactive airway system and alveolar simplification in adult HER4 heart (2/2) animals (10). In the fetal lung, the deletion of pulmonary ErbB4 leads to an overall delayed progression of structural and functional lung development, including the delayed expression of surfactant protein B (Sftpb). This delay is most prominent at the transition from the canalicular to the saccular stage on Embryonic Day 17. Delayed saccular development, with an increased mesenchymal area around the airspaces and a delayed onset of surfactant synthesis and Sftpb expression in HER4 heart (2/2) lungs, con...

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Section: Discussionmentioning

confidence: 99%

Neuregulin Receptor ErbB4 Functions as a Transcriptional Cofactor for the Expression of Surfactant Protein B in the Fetal Lung

Zscheppang¹,

Dörk²,

Schmiedl

et al. 2011

Am J Respir Cell Mol Biol

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“…Because blood flow increases extracellular glutamate levels to concentrations that are lethal to neurons, many studies target glutamate signaling transmission as a treatment for stroke. A large number of preclinical studies have demonstrated a beneficial effect of NMDA receptor antagonist administration to treat and/or prevent ischemic strokerelated neurodegeneration [101][102][103][104][105], but none of these therapeutic strategies have demonstrated success in the clinic [106,107]. Inappropriate design, incorrect dosing concentrations, improper selection of drugs, and difficulties in treating patients within a given period of time immediately after the ischemic insult certainly have limited the success of these treatment.…”

Section: Strokementioning

confidence: 99%

Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition

Rahn

Slusher²,

Kaplin³

2012

CMC

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Glutamate, first identified in 1866, is the primary excitatory neurotransmitter in the brain. While it is critically important in many highly regulated cortical functions such as learning and memory, glutamate can be much like the magic the Sorcerer's Apprentice used in Goethe's poem: when conjured under unregulated conditions glutamate can get quickly out of control and lead to deleterious consequences. Two broad types of glutamate receptors, the ionotropic and metabotropic, facilitate glutamatergic neurotransmission in the CNS and play key roles in regulating cognitive function. Excessive activation of these receptors leads to excitotoxicity, especially in brain regions that are developmentally and regionally vulnerable to this kind of injury. Dysregulation of glutamate signaling leads to neurodegeneration that plays a role in a number of neuropsychiatric diseases, prompting the development and utilization of novel strategies to balance the beneficial and deleterious potential of this important neurotransmitter. Inhibition of the enzyme glutamate carboxypeptidase II (GCPII) is one method of manipulating glutamate neurotransmission. Positive outcomes (decreased neuronal loss, improved cognition) have been demonstrated in preclinical models of ALS, stroke, and Multiple Sclerosis due to inhibition of GCPII, suggesting this method of glutamate regulation could serve as a therapeutic means for treating neurodegeneration and cognitive impairment.

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“…Rats were anesthetized with an intraperitoneal injection of chloral hydrate (300 mg/kg). Permanent middle cerebral artery occlusion (pMCAO) was induced using the suture occlusion model as described previously [17]. Briefly, the right common carotid artery (CCA) and external carotid artery (ECA) were carefully exposed through a ventral midline neck incision.…”

Section: Animal Modelmentioning

confidence: 99%

Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia

Yang

Shu

et al. 2009

Neurochem Res

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This investigation was performed to determine the neuroprotective effect of baicalin on permanent cerebral ischemia injury in rats and the potential mechanisms in this process. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). The rats were then received intraperitoneal injection with baicalin (10, 30 and 100 mg/kg) or vehicle. Morphological characteristic, neurological deficit scores, cerebral infarct volume and the enzymatic activity of myeloperoxidase (MPO) were measured 24 h after pMCAO. The mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by RT-PCR. Neuronal apoptosis was determined by TUNEL staining and Western blot. Baicalin (30 and 100 mg/kg) reduced neurological deficit scores and cerebral infarct volume 24 h after pMCAO. Baicalin significantly decreased the enzymatic activity of MPO and the expression of iNOS mRNA and COX-2 mRNA in rat brain, it also significantly inhibited neuronal apoptosis and the expression of cleaved caspase-3 protein after pMCAO. Our results suggested that baicalin possesses potent anti-inflammatory and anti-apoptotic properties and attenuates cerebral ischemia injury. This protection might be associated with the downregulated expression of iNOS mRNA, COX-2 mRNA, and cleaved caspase-3 protein.

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Neuroprotection by neuregulin-1 in a rat model of permanent focal cerebral ischemia

Cited by 76 publications

References 41 publications

Neuregulin Receptor ErbB4 Functions as a Transcriptional Cofactor for the Expression of Surfactant Protein B in the Fetal Lung

Neuregulin Receptor ErbB4 Functions as a Transcriptional Cofactor for the Expression of Surfactant Protein B in the Fetal Lung

Glutamate in CNS Neurodegeneration and Cognition and its Regulation by GCPII Inhibition

Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia

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