ABSTRACT
Multiple cellular components, including neuronal, glial and endothelial cells, are involved in the sophisticated pathological processes following central nervous system injury. The pathological process cannot reduce damage or improve functional recovery by merely targeting the molecular mechanisms of neuronal cell death after central nerve system injuries. Eph receptors and ephrin ligands have drawn wide attention since the discovery of their extensive distribution and unique bidirectional signaling between astrocytes and neurons. The roles of Eph/ephrin bidirectional signaling in the developmental processes have been reported in previous research. Recent observations suggest that Eph/ephrin bidirectional signaling continues to be expressed in most regions and cell types in the adult central nervous system, playing diverse roles. The Eph/ephrin complex mediates neurogenesis and angiogenesis, promotes glial scar formation, regulates endocrine levels, inhibits myelin formation and aggravates inflammation and nerve pain caused by injury. The interaction between Eph and ephrin is also considered to be the key to angiogenesis. This review focuses on the roles of Eph/ephrin bidirectional signaling in the repair of central nervous system injuries.
ABSTRACT
Background. Subacute combined degeneration (SCD) is a rare cause of demyelination of the dorsal and lateral columns of spinal cord and is a neurogenic complication due to cobalamin deficiency. Anemia of chronic disease (ACD) occurs in patients with acute or chronic immune activation, including infective endocarditis. It remains to be elucidated whether ACD patients are more sensitive to suffer from SCD. Little cases about SCD patients accompanied with ACD have been reported till now. Here we reported a 36-year-old man with SCD with a medical history of mitral inadequacy over 20 years, who was admitted and transported from another hospital to our hospital due to an 8-month history of gait disturbance, lower limb weakness and paresthesia, and loss of proprioception. Significant laboratory results and echocardiography suggest iron deficiency anemia and infective endocarditis (IE). The SCD diagnosis was confirmed by MRI, which showed selective demyelination in the dorsal and lateral columns of spinal cord. In conclusion, the ACD patients may suffer from SCD, which can be diagnosed by 3 Tesla magnetic resonance imaging.
ABSTRACT
Excessive astrogliosis is a major impediment to axonal regeneration in CNS disorders. Overcoming this inhibitory barrier of reactive astrocytes might be crucial for CNS repair. Up-regulation and activation of epidermal growth factor receptor (EGFR) has been shown to trigger quiescent astrocytes into reactive astrocytes in response to several neural injuries. In this study, we investigated the effects of EGFR blockade in cultured astrocytes exposure to oxygen-glucose deprivation/reoxygenation (OGD/R) and in the rat middle cerebral artery occlusion (MCAO) model. Astrocytes in primary culture were used for OGD/R model and adult male Sprague-Dawley rats were used for MCAO model. Cell cycle progression of astrocytes in vitro was studied by flow cytometric analysis. Expression of phosphorylated epidermal growth factor receptor (p-EGFR), glial fibrillary acidic protein (GFAP), and cell proliferation-related molecules in vitro and in vivo were evaluated by immunostaining and western blot analysis. Neuronal apoptosis after MCAO was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method. Neurologic scores and infarct volumes post-ischemia were assessed in the rat MCAO model. Astrocytes became activated in the cultured astrocytes exposure to OGD/R and in the rat brain after MCAO, accompanied with phosphorylation of EGFR. EGFR blockade significantly decreased expression of p-EGFR, inhibited cell cycle progression of astrocytes, and reduced reactive astrogliosis in vitro and in vivo. EGFR inhibition also reduced infarct volumes and improved neurologic scores of rats after MCAO. Our findings indicated that blocking EGFR pathway might attenuate reactive astrogliosis through inhibiting cell cycle progression and protect against ischemic brain injury in rats.
