The Molecular Mechanism and Neuroprotective Effect of Dihydrocapsaicin-Induced Mild Hypothermia After Cardiopulmonary Resuscitation in Rats

Abstract

To investigate the molecular mechanism of dihydrocapsaicin (DHC)-induced mild hypothermia in rats, and to compare its protective effect on the central nervous system with that of a conventional method of inducing hypothermia, 24 healthy male Sprague Dawley rats were randomly divided into four groups based on the following conditions: control group, cardiopulmonary resuscitation (CPR) group, body surface cooling group, and DHC group. Tracheal clipping was used to mimic asphyxia arrest. Rats were assessed for their neurological deficit scores. After sacrifice, immunohistochemical staining was used to examine caspase-3 expression in the cerebral cortex and TRPV1 (transient receptor potential vanilloid subfamily, member 1) expression in the hypothalamus. Terminal TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to evaluate cell apoptosis in the cerebral cortex. Furthermore, intracellular Ca concentration in the hypothalamus and arginine vasopressin (AVP) concentration in ventral septal tissues were also detected in these four groups. Results of our study showed that neurological deficit scores in the DHC group were significantly higher than those in the CPR and body surface cooling groups (p < 0.05). Caspase-3 expression in the cerebral cortex of control group rats was significantly lower than that in other three groups (p < 0.05). Hypothalamic TRPV1 expression, hypothalamic intracellular Ca concentration, and AVP concentration in the ventral septum in the DHC group were significantly higher than that in the other three groups (p < 0.05). Within these three groups, there were significantly fewer apoptotic cells in the DHC and body surface cooling group rats than in the CPR group rats (p < 0.05). DHC has the neuroprotective effect. DHC induced mild hypothermia and reduces apoptosis through a mechanism whereby DHC activates TRPV1 on hypothalamic cells to cause a large Ca influx, which alters corresponding physiological functions and causes the release of AVP to induce hypothermia.

A Direct Comparison of Physical Versus Dihydrocapsaicin-Induced Hypothermia in a Rat Model of Traumatic Spinal Cord Injury

“…The experiments with calves showed that IV infusion of DHC could maintain mild hypothermia (−3°C or more) for more than 12 hours, a result that is important because, unlike laboratory rodents, large animals and humans have a surface area-to-mass ratio that is relatively small, which favors heat retention. DHC has been used to induce pharmacological hypothermia in animal models of cardiac arrest (Junyun et al , 2016 ; Zhong et al , 2018 ) and cerebral ischemia (Cao et al , 2014 , 2017 ; Janyou et al , 2017 ) with favorable results, but had not been examined previously in models of SCI.…”

“…When studied in vitro , under conditions in which lowered temperature cannot contribute, DHC acts as an antioxidant (Rosa et al , 2002 ; Nascimento et al , 2014 ) and it inhibits in vitro platelet aggregation and thromboxane B2 formation (Adams et al , 2009 ; Almaghrabi et al , 2014 , 2018 ). In models of focal (Cao et al , 2014 , 2017; Janyou et al , 2017 , 2020 ; Wu et al , 2017 ) and global (Junyun et al , 2016 ; Zhong et al , 2018 ) cerebral ischemia, several biochemical effects of DHC have been reported that are difficult to disentangle from hypothermia per se. Critically, however, the salutary effects of DHC in ischemia are not observed in TRPV1 knockout mice, strongly implicating TRPV1 as a principal mechanism of action (Cao et al , 2014 ).…”

“…Dihydrocapsaicin (DHC), the capsaicinoid most commonly studied (Feketa and Marrelli, 2015 ), has been shown to reliably induce mild-to-moderate hypothermia following IV administration in mammals via its action as an agonist at transient receptor potential cation channel subfamily V member 1 (TRPV1) receptors (Fosgerau et al , 2010b ; Cao et al , 2014 ). DHC has been used to induce pharmacological hypothermia in animal models of cardiac arrest (Junyun et al , 2016 ; Zhong et al , 2018 ) and cerebral ischemia (Cao et al , 2014 , 2017; Janyou et al , 2017 ) with favorable results, but has not been examined in models of SCI.…”

Pungency Perception and the Interaction with Basic Taste Sensations: An Overview

“…Protective mechanisms of brain injury after cardiac arrest and resuscitation; Markedly abrogated TNFα-induced expression of the adhesion molecules VCAM-1 and ICAM-1, IL-6 production, and activation of NFκB, Reduced inflammatory damage in human vascular endothelial cell cultures. [23,24] Piperine Anticancer Inhibited the epithelial-mesenchymal transition (EMT) activated by TGF-β and prevented the invasion and metastasis of HepG2 cells in hepatocellular carcinoma.…”