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

Abstract

Dexmedetomidine (Dex) is a sedative and analgesic agent that is widely administered to patients admitted to the intensive care unit, and has been demonstrated to result in hypothermia. Many patients have been revealed to benefit from therapeutic hypothermia, which can mitigate cerebral ischemia/reperfusion (I/R) injury following successful cardiopulmonary resuscitation. However, studies investigating the efficacy of Dex in I/R treatment is lacking. The present study aimed to investigate the efficacy of Dex in mitigating neuronal damage, and to determine the possible mechanism of its effects in a rat model of cardiac arrest (CA). CA was induced in Sprague-Dawley rats by asphyxiation for 5 min. Following successful resuscitation, the surviving rats were randomly divided into two treatment groups; one group was intraperitoneally administered with Dex (D group), whereas the control group was treated with normal saline (N group). Critical parameters, including core temperature and blood pressure were monitored following return of spontaneous circulation (ROSC). Arterial blood samples were collected at 10 min after surgery (baseline) 30 and 120 min post-ROSC; and neurological deficit scores (NDS) of the rats were taken 12 or 24 h after ROSC prior to euthanasia. The hippocampal tissue was then removed for analysis by histology, electron microscopy and western blotting. Rats in the D group exhibited a lower core temperature and higher NDS scores compared with the N group (P<0.05). In addition, Dex injection resulted in reduced expression of apoptotic and autophagy-associated factors in the hippocampus (P<0.05). Dex treatment induced hypothermia and improved neurological function in rats after ROSC following resuscitation from CA by inhibiting neuronal apoptosis and reducing autophagy, which suggested that Dex may be a potential therapy option for patients with CA.

Liraglutide attenuates post-cardiac arrest brain injury by inhibiting autophagy and ferroptosis

“…Those results demonstrate that overactivation of autophagy may lead to apoptosis and ferroptosis, whereas inhibition of autophagy may attenuate apoptosis and improve neurological function. Previous studies [54] and the results of this study have demonstrated that overactivation of autophagy could provoke apoptosis and ferroptosis, and inhibition of autophagy could alleviate PCABI.…”

Mild hypothermia combined with dexmedetomidine reduced brain, lung, and kidney damage in experimental acute focal ischemic stroke

“…Dexmedetomidine associated with hypothermia reduces brain damage, improves neurological outcome, and increases the survival rate of the hippocampal CA1 neurons, compared to saline [ 46 ]. The increase in expression of ZO-1 in mild hypothermia + dexmedetomidine compared to normothermia + dexmedetomidine may be attributed to hypothermia alleviating neurocyte apoptosis [ 47 ].…”

Hypothermia Following Spinal Anesthesia in an Infant: Potential Impact of Intravenous Dexmedetomidine and Intrathecal Clonidine

“…The hypothermia was corrected by the placement of an overhead radiant warmer and a decrease of the dexmedetomidine infusion to 0.2 µg/kg/h. Additional evidence for the potential impact of α 2 -adrenergic agonists on thermoregulation and their potential role in the development of hypothermia is provided by animal data [20][21][22].…”