RNase alleviates neurological dysfunction in mice undergoing cardiac arrest and cardiopulmonary resuscitation

Abstract

Cardiac arrest (CA) is one of the leading lethal factors. Despite cardiopulmonary resuscitation (CPR) procedure has been consecutively improved and lots of new strategies have been developed, neurological outcome of the patients experienced CPR is still disappointing. Ribonuclease (RNase) has been demonstrated to have neuroprotective effects in acute stroke and postoperative cognitive impairment, possibly through acting against endogenous RNA that released from damaged tissue. However, the role of RNase in post-cardiac arrest cerebral injury is unknown. In the present study, we investigated the role of RNase in neurological outcome of mice undergoing 5 minutes of CA and followed by CPR. RNase or the same dosage of normal saline was administrated. We found that RNase administration could: 1) improve neurologic score on day 1 and day 3 after CA/CPR performance; 2) improve memory and learning ability on day 3 after training in contextual fear-conditioning test; 3) reduce extracellular RNA (exRNA) level in plasma and hippocampus tissue, and hippocampal cytokines mRNA production on day 3 after CA/CPR procedure; 4) attenuate autophagy levels in hippocampus tissue on day 3 after CA/CPR procedure. In conclusion, RNase could improve neurological function by reducing inflammation response and autophagy in mice undergoing CA/CPR.

RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation

“…Besides, 20, 15 and 12 of 25 mice survived in the CA/CPR group on day 1, 2 and 3 after CA/CPR procedures, respectively. The survival rates were 80%, 60%, and 48%, respectively, which was similar to previously published literature [ 17 , 18 ]. In our settings, the mice received five minutes of CA, and subsequent CPR performance exhibited a remarkable abnormality in cognitive function ( Figure 1E ).…”

“…In this study, we demonstrated that mice surviving after 5 minutes of CA displayed remarkable abnormalities in the contextual fear-conditioning test and neurologic score ( Figure 1 ). The survival rate on day 3 after CA/CPR was 48%, which was quantitatively in good agreement with earlier reports [ 17 , 18 ]. It was indicated that the animal model of CA/CPR in our study was reliable.…”

“…The current study aimed to explore which lncRNAs may be implicated in the pathogenesis of cognitive impairment after CA/CPR. We established a CA/CPR mouse model as previously reported [ 17 , 18 , 24 ], and identified significantly deregulated lncRNAs and mRNAs (fold change ≥ 2, p < 0.05) in the hippocampal samples. Our results showed that 1162 mRNAs and 1920 lncRNAs were significantly differentially expressed between the two groups.…”

“…As a regulatory factor, lncRNA was proved to be closely associated with cellular inflammation, excessive reactive oxygen species (ROS) and apoptosis [ 13 , 30 , 31 ]. More importantly, plenty of studies suggested that reducing neuronal apoptosis or inflammation could improve cognitive function after CA/CPR [ 5 , 18 , 32 ]. In the context of cognitive deficits after CA/CPR, we found that several inflammation and apoptosis-related genes had abnormal expression levels, which may be potentially targeted by lncRNAs.…”

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

“…Although CA can lead to ischemia/reperfusion (I/R) injury in every organ in the body, it is especially detrimental to the brain and the heart. The principal pathological cause of organ damage is excessive apoptosis and autophagy (4,5), the extent of which has been found to correlate with poor neurological prognosis (6)(7)(8). A number of studies have demonstrated that hypothermia can attenuate neurological damage following I/R injury by reducing neural apoptosis and preventing autophagy overactivation (4,9,10).…”