Pengyu Pan1,2, Jie Qu1, Qiang Li1, Rongwei Li1, Yang Yang1, Shilun Zuo1, Xin Liu1, Hua Feng1,3,4, Yujie Chen1,4. 1. Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing, 400038 China. 2. Department of Neurosurgery, General Hospital of Shenyang Military Command, Shenyang, 110016 China. 3. State Key Laboratory of Trauma, Burn and Combined Injury, Third Military Medical University, Chongqing, 400038 China. 4. Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration, Southwest Hospital, Third Medical University, Chongqing, 400038 China.
Abstract
BACKGROUND: Recent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage (SAH). However, pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes. Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks, we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH. METHODS: In our experiments, platelet-derived growth factor B (PDGF-B) retention motif knockout (PDGF-Bret/ret) mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression. Neurological score, SAH grade, hematoxylin-eosin staining, and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery, as well as western blotting and immunofluorescence staining for underlying molecular expressions. RESULTS: We found that neonatal PDGF-Bret/ret mice exhibited pulmonary atelectasis 12 h after birth. Further investigation showed a decrease in PaO2/FiO2 and lung-specific surfactant proteins in adult PDGF-Bret/ret mice. These dysfunctions were much worse than those in wild-type mice at 24 h after SAH. PDGF-B overexpression alleviated pulmonary dysfunction after SAH. CONCLUSIONS: These results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH. Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.
BACKGROUND: Recent advances in surgical and neuroprotective strategies could effectively manage the pathophysiological progression of subarachnoid hemorrhage (SAH). However, pulmonary dysfunction frequently occurs in SAH patients with an increased risk of unsatisfactory outcomes. Based on the similar microvascular structures in the blood-air barrier and blood-brain barrier and possible brain-lung crosstalks, we believe that pericytes may be involved in both neurological and pulmonary dysfunction after SAH. METHODS: In our experiments, platelet-derived growth factor B (PDGF-B) retention motif knockout (PDGF-Bret/ret) mice and adeno-associated virus PDGF-B were employed to show the involvement of pericyte deficiency and PDGF-B expression. Neurological score, SAH grade, hematoxylin-eosin staining, and PaO2/FiO2 ratio analysis were performed to evaluate the neurological deficits and pulmonary functions in endovascular perforation SAH models at 24 h after surgery, as well as western blotting and immunofluorescence staining for underlying molecular expressions. RESULTS: We found that neonatal PDGF-Bret/ret mice exhibited pulmonary atelectasis 12 h after birth. Further investigation showed a decrease in PaO2/FiO2 and lung-specific surfactant proteins in adult PDGF-Bret/ret mice. These dysfunctions were much worse than those in wild-type mice at 24 h after SAH. PDGF-B overexpression alleviated pulmonary dysfunction after SAH. CONCLUSIONS: These results suggested pulmonary dysfunction after SAH and the pivotal role of PDGF-B signaling for the pathophysiological process and future therapeutic targets of pulmonary injury treatment after SAH. Further studies are needed for pathophysiological investigations and translational studies on pulmonary injuries after SAH.
Authors: Cecil O Borel; Andy McKee; Augusto Parra; Michael M Haglund; Amy Solan; Vikas Prabhakar; Huaxin Sheng; David S Warner; Laura Niklason Journal: Stroke Date: 2003-02 Impact factor: 7.914
Authors: Per Lindblom; Holger Gerhardt; Stefan Liebner; Alexandra Abramsson; Maria Enge; Mats Hellstrom; Gudrun Backstrom; Simon Fredriksson; Ulf Landegren; Henrik C Nystrom; Goran Bergstrom; Elisabetta Dejana; Arne Ostman; Per Lindahl; Christer Betsholtz Journal: Genes Dev Date: 2003-08-01 Impact factor: 11.361