Nogo-A/Pir-B/TrkB Signaling Pathway Activation Inhibits Neuronal Survival and Axonal Regeneration After Experimental Intracerebral Hemorrhage in Rats

• Published in: Journal of molecular neuroscience Vol. 69; no. 3; pp. 360 - 370
• Main Authors: Liu, Yinlong, Ma, Chao, Li, Haiying, Shen, Haitao, Li, Xiang, Fu, Xi’an, Wu, Jiang, Chen, Gang
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2019; Springer Nature B.V
• Subjects: Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Brain; Brain - pathology; Brain injury; Carbazoles - toxicity; Cell Biology; Cell Death; Cerebral Hemorrhage - chemically induced; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - pathology; Cerebral Hemorrhage - physiopathology; Cognition Disorders - etiology; Cognition Disorders - prevention & control; Cognitive ability; Head injuries; Hemorrhage; Immunofluorescence; Indole Alkaloids - toxicity; Kinases; Lesions; Male; Maze Learning; Motor Activity; Myelin; Nerve Tissue Proteins - metabolism; Neurochemistry; Neurology; Neuronal Outgrowth - physiology; Neurons - pathology; Neurons - physiology; Neuroprotective Agents - therapeutic use; Neurosciences; Nogo protein; Nogo Proteins - biosynthesis; Nogo Proteins - physiology; Proteins; Proteomics; Quinolines - therapeutic use; Rats; Rats, Sprague-Dawley; Receptor, trkB - physiology; Receptors, Immunologic - biosynthesis; Receptors, Immunologic - physiology; Regeneration; Signal Transduction; Survival; TrkB receptors; Tropomyosin; Up-Regulation; Growth-associated protein 43; Nogo-A; Neuron cell death; Intracerebral hemorrhage; Tropomyosin receptor kinase B; Axonal regeneration
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-019-01365-1

Intracerebral hemorrhage (ICH) leads to widespread pathological lesions in the brain, especially impacting neuronal survival and axonal regeneration. This study aimed to elucidate whether the Nogo-A (a myelin-related protein)/paired immunoglobulin-like receptor B (Pir-B)/tropomyosin receptor kinase B (TrkB) pathway could exert a regulatory effect in ICH. An ICH model was first established in Sprague Dawley rats, followed by different administrations of vehicle, k252a, or NSC 87877. The Morris water maze test was performed to observe ICH-induced cognitive dysfunction in rats. Rats in the ICH + NSC 87877 group showed better cognitive performance compared with those injected with vehicle or k252a. Neurobehavioral scores were identical. By harvesting brain tissues at different time points after ICH, we detected the expression levels of Nogo-A and PirB with western blot and immunofluorescence and found that they were markedly upregulated at 48 h after ICH. TUNEL and Fluoro-Jade B staining showed that NSC 87877 treatment attenuated ICH-induced apoptosis and neuronal death, whereas k252a treatment aggravated these pathological changes. The expression levels of growth-associated protein 43 (GAP43) and neurofilament 200 (NF200) were higher in the ICH + NSC 87877 group compared with the ICH + vehicle group, but were lower in the ICH + k252a group. Finally, we confirmed the protective role of p-TrkB/TrkB in ICH by western blot. To sum up, our study identified the inhibitory role of the Nogo-A/PirB/TrkB pathway in ICH; however, p-TrkB/TrkB may serve as a potential target for secondary brain injury post-ICH.