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Transcriptional profiling in rat hair follicles following simulated Blast insult: a new diagnostic tool for traumatic brain injury.

ABSTRACT: With wide adoption of explosive-dependent weaponry during military activities, Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become a significant medical issue. Therefore, a robust and accessible biomarker system is in demand for effective and efficient TBI diagnosis. Such systems will also be beneficial to studies of TBI pathology. Here we propose the mammalian hair follicles as a potential candidate. An Advanced Blast Simulator (ABS) was developed to generate shock waves simulating traumatic conditions on brains of rat model. Microarray analysis was performed in hair follicles to identify the gene expression profiles that are associated with shock waves. Gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used to identify cell processes and molecular signaling cascades affected by simulated bomb blasts. Enrichment analyses indicated that genes with altered expression levels were involved in central nervous system (CNS)/peripheral nervous system (PNS) responses as well as signal transduction including Ca2+, K+-transportation-dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as affected by shock waves in the hair follicles have been previously reported to be TBI responsive in other organs such as brain and blood. The results suggest that the hair follicle has some common TBI responsive molecular signatures to other tissues. Moreover, various TBI-associated diseases were identified as preferentially affected using a gene network approach, indicating that the hair follicle may be capable of reflecting comprehensive responses to TBI conditions. Accordingly, the present study demonstrates that the hair follicle is a potentially viable system for rapid and non-invasive TBI diagnosis.

SUBMITTER: Zhang J

PROVIDER: S-EPMC4138085 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeTelogen (resting phase) hair follicles (HFs) are more radioresistant than their anagen (growth phase) counterparts. Fibroblast growth factor (FGF) 18 is strongly expressed in telogen HFs to maintain the telogen phase, whereas several other FGFs exert radioprotective effects; however, the role of FGF18 in the radioresistance of HFs remains unknown. This study focused on clarifying the role of FGF18 in the radioresistance of telogen HFs and its potential as a radioprotector.Methods and materialsBALB/c mice with telogen or plucking-induced anagen HFs were exposed to total body irradiation with γ-rays at 4 to 12 Gy after intraperitoneal treatment with FGF18 or an FGF receptor inhibitor. A time course analysis was performed histologically and hair growth was observed 14 or 15 days after depilation. Skin specimens were analyzed by DNA microarrays and Western blotting.ResultsTelogen irradiation at 6 Gy resulted in transient cell growth arrest, leading to successful hair growth, whereas anagen irradiation failed to promote hair growth. Telogen irradiation did not induce apoptosis in HFs or reduce HF stem cells, whereas anagen irradiation induced apoptosis and reduced stem cell numbers. The Inhibition of FGF receptor signaling during the telogen phase promoted HF cell proliferation; however, hair failed to grow after irradiation. In contrast, recombinant FGF18 induced transient cell growth arrest after anagen irradiation with enhanced DNA repair, leading to the inhibition of apoptosis, maintenance of HF stem cells, and successful hair growth. Moreover, FGF18 reduced the expression levels of genes promoting G2/M transition as well as the protein expression levels of cyclin B1 and cdc2 in skin, and induced G2/M arrest in the keratinocyte cell line HaCaT.ConclusionsThese results suggest that FGF18 signaling mediates radioresistance in telogen HFs by arresting the cell cycle, and that FGF18 has potential as a radioprotector for radiation-induced alopecia.

Project description:Traumatic pericarditis (TP) remains a serious problem facing bovine producers; particularly in the developing countries; causing severe economic losses. This study was carried out on 47 buffaloes including; control buffaloes (n = 20) and buffaloes with TP (n = 27) at Assiut governorate, Egypt. All animals were subjected to thorough clinical examination, whole blood profiling, blood serum biochemical assays, and radiographic and ultrasonographic examinations. The recorded ultrasonographic findings included; the contractility, contour and shape of the reticulum, shape and size of the heart and spleen involvement. All data were statistically analysed. Buffaloes with TP showed lymphocytic leucocytosis, increase in serum activities of AST, hyperproteinaemia, hypoalbuminaemia and hyperglobulinaemia. Radio-opaque metal foreign bodies, cardiomegaly and loss of the normal cardiac shape and contour were the most common radiographic findings in the diseased buffaloes. Ultrasonographically, the diseased buffaloes showed either acute pericarditis (n = 10) or chronic suppurative pericarditis (n = 17). Complete cessation of reticular contractions (0/3 min) and displacement of the reticulum from the diaphragm by a distance about 2.6-4.5 cm were the most common ultrasonographic findings of both types of pericarditis. In addition, the reticulum had uneven contour and the heart showed characteristic changes in its size, shape and contractility that was either accelerated or reduced. Reticular abscesses and peritoneal effusions were also imaged in all diseased buffaloes. In acute TP; the affected heart was enlarged with strong and clear cardiac contractions. Accumulation of hypoechoic fluids interspersed with echogenic deposits of fibrin within heart tissue and pericardium was observed. In chronic suppurative pericarditis, cardiomegaly, thickening of the cardiac wall and loss of the characteristic recognisable heart shape were the common ultrasonographic findings. Accumulation of hypoechoic fluids (usually pus) interspersing with echogenic deposits of fibrin within the pericardium, ventricles, atria and valves was also observed. In conclusion, ultrasonography with the aids of other diagnostic tools such as clinical findings, laboratory analysis and radiography has a high efficacy in evaluation of diseased buffaloes with TP.

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Transcriptional profiling in rat hair follicles following simulated Blast insult: a new diagnostic tool for traumatic brain injury.

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