Calcitonin gene‑related peptide has protective effect on brain injury induced by heat stroke in rats

Abstract

Heat stroke often leads to multiple organ dysfunction syndrome (MODS) with a neurological morbidity of 30%. Current studies suggested that pathophysiological responses to heat stroke may be due to a systemic inflammatory response syndrome and a series of peptidergic nerve reactions. The mechanisms underlying the high neurological morbidity in heat stroke have remained largely elusive. In recent years, calcitonin gene-related peptide (CGRP) has been considered to have a positive role in central nervous system injury. The present study investigated the influence of CGRP on brain injury induced by heat stroke. A rat model of heat stroke was established in a pre-warmed artificial climate chamber with a temperature of 35.5±0.5°C and a relative humidity of 60±5%. The rectal core temperature (Tc) was monitored. Heat stress was halted at a Tc of no more than 41°C A bolus injection of CGRP was administered to each rat in the HS+CGRP group and a bolus injection of CGRP8-37 was administered to each rat in the HS+CGRP8-37 group after heat stress. After 2 h, electroencephalograms were recorded and the pathological morphology of brain tissue as well as brain cell apoptosis and caspase-3 protein levels in the brain were measured. The EEG of rats in the HS+CGRP group was characterized by a short- to long-term α-wave and low-voltage β-waves as well as a large amount of intermittent δ- and θ-waves. Compared with the HS group, the θ-wave decreased and the α-wave increased significantly (P<0.05). Slight pathological damage of nerve cells appeared in the HS+CGRP group. Greater damage was observed in HS+CGRP8-37 group with neural cell shrinkage, volume reduction, nuclear pyknosis, disappearance of part of the nuclear membrane and cell necrosis. In the HS+CGRP group, apoptotic cells and caspase-3 protein in the brain were significantly decreased when compared with those in the HS group (P<0.05), while they were significantly increased in the HS+CGRP8-37 group (P<0.05 vs. HS group). The results of the present study reflected that CGRP has a protective effect on early-stage brain injury induced by heat stroke in rats.

Microglial exosomal miR-466i-5p induces brain injury via promoting hippocampal neuron apoptosis in heatstroke

“…For surviving patients, neurological sequelae are also an important factor in the quality of life. In our previous studies, we found that neuronal apoptosis is an important basis for brain injury in heat stroke ( 9 , 10 ). However, due to the particular intracranial structure and complex interactions between cells, the pathophysiological mechanism of brain injury in the HS is still unclear, which is a significant difficulty in treating heatstroke.…”

Differences in Gene Expression Profiles and Phenotypes of Differentiated SH-SY5Y Neurons Stably Overexpressing Mitochondrial Ferritin

“…CGRP expression is high in the CNS suggesting neurotransmitter activity. CGRP was shown to provide significant protective properties in different experimental systems, including heat injury and ischemia/reperfusion in rats and overexpression in Schwann cells subject to oxidative stress (Russell et al, 2014; Wu et al, 2015; Yang et al, 2016; Lu et al, 2017). Secretogranin II (SCG2)(Chromagranin C) is also a neuroendrocrine secretory protein that is cleaved to form the peptide secretoneurin.…”

Alpha-Calcitonin Gene Related Peptide: New Therapeutic Strategies for the Treatment and Prevention of Cardiovascular Disease and Migraine

“…However, intramyocardial injection of adenovirus encoding the CGRP gene reduced myocardial infarct size and plasma LDH level in both non-diabetic and diabetic mice (Zheng et al, 2012). α-CGRP has been shown to prevent I/R damage in other tissues such as the intestines, kidneys, and brain (Song et al, 2009;Liu et al, 2011;Lu et al, 2017). When central organs, like the heart and liver, are exposed to ischemia, α-CGRP release may serve to both prevent damage to these organs and protect other organ systems, such as the intestines, from subsequent injury via reflexive neuronal release.…”