Fasudil alleviates brain damage in rats after carbon monoxide poisoning through regulating neurite outgrowth inhibitor/oligodendrocytemyelin glycoprotein signalling pathway

Abstract

Carbon monoxide (CO) poisoning can lead to many serious neurological symptoms. Currently, there are no effective therapies for CO poisoning. In this study, rats exposed to CO received hyperbaric oxygen therapy, and those in the Fasudil group were given additional Fasudil injection once daily. We found that the escape latency in CO poisoning group (CO group) was significantly prolonged, the T1/Ttotal was obviously decreased, and the mean escape time and the active escape latency were notably extended compared with those in normal control group (NC group, P < 0.05). After administration of Fasudil, the escape latency was significantly shortened, T1/Ttotal was gradually increased as compared with CO group (>1 week, P < 0.05). Ultrastructural damage of neurons and blood‐brain barrier of rats was serious in CO group, while the structural and functional integrity of neuron and mitochondria maintained relatively well in Fasudil group. Moreover, we also noted that the expressions of neurite outgrowth inhibitor (Nogo), oligodendrocyte‐myelin glycoprotein (OMgp) and Rock in brain tissue were significantly increased in CO group, and the elevated levels of the three proteins were still observed at 2 months after CO poisoning. Fasudil markedly reduced their expressions compared with those of CO group (P < 0.05). In summary, the activation of Nogo‐OMgp/Rho signalling pathway is associated with brain injury in rats with CO poisoning. Fasudil can efficiently down‐regulate the expressions of Nogo, OMgp and Rock proteins, paving a way for the treatment of acute brain damage after CO poisoning.

Clinical Characteristics of Visual Dysfunction in Carbon Monoxide Poisoning Patients

“…Carbon monoxide (CO) is the most common asphyxiating gas that causes toxic death in life and work. Once poisoned, it can lead to multiple system dysfunction in patients, among which brain and myocardial damages are the most serious and become the main death factors in the acute phase [ 1 , 2 ]. Despite the improvement of the clinical performance and the recovery of consciousness in acute CO poisoning patients, some cases still appear as series of encephalopathy symptoms again within 2–60 days of “false recovery period.” The latter is called the delayed encephalopathy after carbon monoxide poisoning (DEACMP) with high death rate and disability rate and seriously affects the life quality of patients and their families [ 3 ].…”

Therapeutic effect and molecular mechanism of Salvia Miltiorrhiza on rats with acute brain injury after carbon monoxide poisoning based on the strategy of internet pharmacology

“…At present, the pathogenesis of brain injury caused by COP is not clear, the core of which lies in the direct ischemia‐hypoxia, the inflammation and immune‐mediated damage and the cellular apoptosis 27 . There are many common targets between acute brain injury caused by COP and ischemic cerebrovascular disease, and ischemia and hypoxia are the most important ones 22 . Previous studies have shown that angiogenesis not only increases blood flow around ischemic regions of the brain, saving dying nerve cells, but also provides oxygen and improves hypoxia.…”

“…Six rats in each group were suffered intraperitoneally the injection of 3% pentobarbital for deep anesthesia, and cardiac perfusion was performed at the given time points above with 200 ml of 0.9% sodium chloride and 4% formaldehyde solution, respectively. Brain tissue was immediately removed from the skull, and paraffin sections were made according to the reports of Li et al 22,23 for Hematoxylin and eosin (H&E) staining, Nissl staining, TUNEL, and Immunohistochemical (IHC) assay.…”

The upregulation of miR-204-3p in LPS-induced acute lung injury aggravated pulmonary endothelial cells apoptosis via targeting sulfatase 2

“…There are various factors causing ALI, such as sepsis, pneumonia, aspiration of gastric contents, severe trauma, acute pancreatitis, and blood transfusion (Brown & Watson, 2018). Indirect ALI is a common consequence of sepsis and about 40% of sepsis patients suffer from ALI (Brown & Watson, 2018;Wang et al, 2019). Sepsis is caused by Gram-negative bacteria and lipopolysaccharide (LPS) plays a key role in the inflammatory response of ALI (Brown & Watson, 2018;Wang et al, 2019).…”

“…Indirect ALI is a common consequence of sepsis and about 40% of sepsis patients suffer from ALI (Brown & Watson, 2018;Wang et al, 2019). Sepsis is caused by Gram-negative bacteria and lipopolysaccharide (LPS) plays a key role in the inflammatory response of ALI (Brown & Watson, 2018;Wang et al, 2019). Therefore, LPS can be used to establish the mouse ALI model.…”