Dataset Information

Nogo-A expression after focal ischemic stroke in the adult rat.

ABSTRACT: The Nogo-A protein is an important inhibitor of axonal remodeling after central nervous system injuries, including ischemic stroke. Interfering with the function of Nogo-A via infusion of a therapeutic anti-Nogo-A antibody after stroke increases neuronal remodeling and enhances functional recovery in rats. In this study, we describe the regional distribution of cortical neurons expressing Nogo-A in normal rats and following middle cerebral artery occlusion (MCAO).Normal and post-MCAO neuronal Nogo-A expression were described via immunohistochemical analyses. All brains were processed for Nogo-A and parvalbumin expression. The level of Nogo-A expression was scored for each cortical area or white matter structure of interest. The number and fluorescent intensity of layer V neurons in contralesional sensorimotor forelimb cortex were also assessed at each time point.Nogo-A expression was observed in both cortical pyramidal neurons and parvalbumin-positive interneurons. Neuronal expression of Nogo-A changed over time in ipsilesional and contralesional cortical areas after MCAO, becoming globally elevated at 28 days after stroke. Nogo-A expression was not observed to fluctuate greatly in the white matter after stroke, with the exception of a transient increase in Nogo-A expression in the external capsule near the stroke lesion.Neuronal Nogo-A expression is significantly increased at 28 days post-MCAO in all examined brain regions. Because of their robust expression of Nogo-A after stroke lesion, both excitatory and inhibitory neurons represent potential targets for anti-Nogo-A therapies in the poststroke cerebral cortex.

SUBMITTER: Cheatwood JL

PROVIDER: S-EPMC3833276 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nogo-A expression after focal ischemic stroke in the adult rat.

Cheatwood Joseph L JL Emerick April J AJ Schwab Martin E ME Kartje Gwendolyn L GL

Stroke 20080508 7

<h4>Background and purpose</h4>The Nogo-A protein is an important inhibitor of axonal remodeling after central nervous system injuries, including ischemic stroke. Interfering with the function of Nogo-A via infusion of a therapeutic anti-Nogo-A antibody after stroke increases neuronal remodeling and enhances functional recovery in rats. In this study, we describe the regional distribution of cortical neurons expressing Nogo-A in normal rats and following middle cerebral artery occlusion (MCAO).< ...[more]

PMID: 18467652

Similar Datasets

Project description:Background. Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results. Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 hours post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions. The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (<1% of differentially expressed genes) validated for this microarray did not reveal any sex differences.

Project description:Soluble Nogo66 receptor-Fc protein (sNgR-Fc) enhances axonal regeneration following central nervous system injury. However, the underlying mechanisms remain unclear. In this study, we investigated the effects of sNgR-Fc on the proliferation and differentiation of neural progenitor cells. The photothrombotic cortical injury model of ischemic stroke was produced in the parietal cortex of Sprague-Dawley rats. The rats with photothrombotic cortical injury were randomized to receive infusion of 400 μg/kg sNgR-Fc (sNgR-Fc group) or an equal volume of phosphate-buffered saline (photothrombotic cortical injury group) into the lateral ventricle for 3 days. The effects of sNgR-Fc on the proliferation and differentiation of endogenous neural progenitor cells were examined using BrdU staining. Neurological function was evaluated with the Morris water maze test. To further examine the effects of sNgR-Fc treatment on neural progenitor cells, photothrombotic cortical injury was produced in another group of rats that received transplantation of neural progenitor cells from the hippocampus of embryonic Sprague-Dawley rats. The animals were then given an infusion of phosphate-buffered saline (neural progenitor cells group) or sNgR-Fc (sNgR-Fc + neural progenitor cells group) into the lateral ventricle for 3 days. sNgR-Fc enhanced the proliferation of cultured neural progenitor cells in vitro as well as that of endogenous neural progenitor cells in vivo, compared with phosphate-buffered saline, and it also induced the differentiation of neural progenitor cells into neurons. Compared with the photothrombotic cortical injury group, escape latency in the Morris water maze and neurological severity score were greatly reduced, and distance traveled in the target quadrant was considerably increased in the sNgR-Fc group, indicating a substantial improvement in neurological function. Furthermore, compared with phosphate-buffered saline infusion, sNgR-Fc infusion strikingly improved the survival and differentiation of grafted neural progenitor cells. Our findings show that sNgR-Fc regulates neural progenitor cell proliferation, migration and differentiation. Therefore, sNgR-Fc is a potential novel therapy for stroke and neurodegenerative diseases, The protocols were approved by the Committee on the Use of Live Animals in Teaching and Research of the University of Hong Kong (approval No. 4560-17) in November, 2015.

Dataset Information

Nogo-A expression after focal ischemic stroke in the adult rat.

Publications

Nogo-A expression after focal ischemic stroke in the adult rat.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure