Hypothermia decreased the expression of heat shock proteins in neonatal rat model of hypoxic ischemic encephalopathy

Abstract

Hypothermia (HT) is a well-established neuroprotective strategy against neonatal hypoxic ischemic encephalopathy (HIE). The overexpression of heat shock proteins (HSP) has been shown to provide neuroprotection in animal models of stroke. We aimed to investigate the effect of HT on HSP70 and HSP27 expression in a neonatal rat model of HIE. Seven-day-old rat pups were exposed to hypoxia for 90 min to establish the Rice-Vannucci model and were assigned to the following four groups: hypoxic injury (HI)-normothermia (NT, 36°C), HI-HT (30°C), sham-NT, and sham-HT. After temperature intervention for 24 h, the mRNA and protein expression of HSP70 and HSP27 were measured. The association between HSP expression and brain injury severity was also evaluated. The brain infarct size was significantly smaller in the HI-HT group than in the HI-NT group. The mRNA and protein expression of both HSPs were significantly greater in the two HI groups, compared to those in the two sham groups. Moreover, among the rat pups subjected to HI, HT significantly reduced the mRNA and protein expression of both HSPs. The mRNA expression level of the HSPs was proportional to the brain injury severity. Post-ischemic HT, i.e., a cold shock attenuated the expression of HSP70 and HSP27 in a neonatal rat model of HIE. Our study suggests that neither HSP70 nor HSP27 expression is involved in the neuroprotective mechanism through which prolonged HT protects against neonatal HIE.

Acquired Resilience: An Evolved System of Tissue Protection in Mammals

“…Al-Fageeh and Smales 378 reviewed detailed molecular mechanisms of the mammalian response to cold. Recent reviews and reports suggest, however, that the protective effect of cold, at least for the oft-studied traumatized CNS, arises not from an upregulation of endogenous protective pathways (such as HSP expression 379 ) but from a downregulation of metabolic demand. 380 In recent years, several studies have addressed with the question whether cold can condition tissues to a subsequent stress.…”

Therapeutic Hypothermia and Neuroprotection in Acute Neurological Disease

“…One example of this is the 70 kD heat shock protein (HSP70), which is known as stress related protein [106]. While HSP70 is upregulated in the various acute cerebral injuries and is known to protect brain from its injuries [211–213], previous studies reported that hypothermia down-regulated its expression [214,215]. Thus, validation of the significance of observed changes by hypothermia would be obviously needed.…”

Grape Seed Proanthocyanidin Extract Down-Regulates Autophagic Proteins (LC3II and Beclin-1) in a Mouse Model of Neonatal Hypoxic-Ischemic Brain Injury

“…The type of brain injury depends on the degree of hypoxia, the duration of hypoxia, and the process of brain maturation [14]. At present, the clinical treatment of HIE involves hypothermia therapy [15], but this therapy only has efficacy on mild HIE injury; the effect is not significant in the treatment of moderate-to-severe HIE injury [16]. Therefore, finding a drug that can target HIE injury has become a difficult problem we need to solve.…”