Induction of heat shock protein 72-like immunoreactivity in the hippocampal formation following transient global ischemia

Jung

Cell Stress and Chaperones

et al. 2017

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.

Section: Discussionmentioning

confidence: 99%

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

Jung

Cell Stress and Chaperones

et al. 2017

J Cereb Blood Flow Metab

“…Though many studies show that HSP70 expres sion is extremely useful for assessing injury (Vass et al, 1988(Vass et al, , 1989Brown et al , 1989;Dwyer et al , 1989;Gonzalez et al, 1989Gonzalez et al, , 1991F erriero et al , 1990;Lowenstein et al, 1990;Sharp et al , 1991a,b), it is unclear whether cells expressing HSP will live or die. Vass et al (1989) in CA3, CA4, and dentate granule cell neurons known to survive, whereas HSP70 was minimally induced in CAl pyramidal neurons, which die.…”

Section: This Induction In the Endothelial Cells In Infarcted Brain Rmentioning

confidence: 99%

Induction of 70-kDa Heat Shock Protein and hsp70 mRNA following Transient Focal Cerebral Ischemia in the Rat

Kinouchi

Sharp

Hill

et al. 1993

Self Cite

185

Summary: Induction of the 70-kDa heat shock protein (HSP70) was demonstrated immunocytochemically in adult rats 4 h to 7 days following temporary middle cere bral artery (MeA) occlusions lasting 30, 60, or 90 min. Maximal HSP70 induction occurred �24 h following ischemia. Thirty minutes of ischemia induced HSP70 in neurons throughout the cortex in the MeA distribution, whereas 90 min of ischemia induced HSP70 in neurons in the penumbra. HSP70 protein was induced in endothelial cells in infarcted neocortex following 60-90 min of MeA occlusion, and HSP70 was induced in endothelial cells in infarcted regions of lateral striatum following 30-90 min Normal rat brain cells do not express the 70-kDa heat shock protein (HSP70) (Vass et aI. , 1988; Brown et aI. , 1989; Gonzalez et aI. , 1989; Sharp et aI. , 1991a,b), which is a product of the hsp70 gene (Hunt and Morimoto, 1985). HSP70 is induced in brain in response to hyperthermia (Brown, 1983;Sprang and Brown, 1987; Barbe et aI. , 1988), epi lepsy (Gonzalez et aI. , 1989; Vass et aI. , 1989; Lo wenstein et aI., 1990), hypoxia-ischemia (Nowak, 1985 Kiessling et aI. , 1986; Vass et aI. , 1988; Dwy er et aI. , 1989; Gonzalez et aI., 1989; Ferriero et aI. , 1990), injection of excitotoxins (Uney et aI. , 1988; Gonzalez et aI. , 1989) 105of MeA occlusion. hsp70 mRNA was induced in the MeA distribution in cortex and to a lesser extent in stri atum at 2 h to 3 days following 60 min of ischemia. It is proposed that brief ischemia induces hsp70 mRNA and HSP70 protein in the cells most vulnerable to ischemia the neurons. HSP70 protein is not induced in most neu rons and glia following 60-90 min of ischemia in areas destined to infarct, whereas it is induced in vascular en dothelial cells. Key Words: Focal brain-hsp70 mRNA Middle cerebral artery-Stress and heat shock protein Stroke.1981; Brown et aI. , 1989). Gonzalez et al. (1989) emphasized the potential value of using HSP70 im munostaining as a sensitive marker of brain cell in jury.HSPs are a family of proteins that perform many functions. Some 60-to 80-kDa HSPs appear to chaperone protein movements across membranes and mediate important protein-protein interactions in normal and stressed cells (Chapell et aI. , 1986;Ellis, 1987; Chirico et aI. , 1988; Cheng et aI. , 1989; Chiang et aI. , 1989; Deshaies et aI. , 1989; Beck mann et aI. , 1990). Some 90-kDa HSPs regulate ste roid receptor availability.Once HSPs are induced, they may prevent pro teins from being denatured (Pelham, 1986) and pro tect cells from subsequent injury (Schlesinger et aI. , 1982;Johnston and Kucey, 1988; Riabowol et aI., 1988). Barbe et al. (1988) provided the first direct evidence for this protective role in the CNS by showing that preinduction in the rabbit retina via systemic hyperthermia is associated with a de crease in light-induced retinal injury. Moreover, mild global cerebral ischemia, sufficient to induce 106 H. KINOUCHI ET AL.HSP70 in the hippocampus, attenuates the hippo campal injury associated with a subsequent severe ischemic...

“…This may be problematic, because there are numerous age-related differences in brain biochemistry, morphology, and electrophysiology. [2][3][4][5][6] Previous studies examining the influence of age on ischemic outcome have produced conflicting results. In experiments involving focal ischemia, infarct volume was consistently increased in aged versus young rats.…”

mentioning

confidence: 99%

Ischemic Preconditioning in 18- to 20-Month-Old Gerbils

Dowden

Corbett

1999

Stroke

Background and Purpose-In young animals, ischemic preconditioning protects CA1 hippocampal neurons against global ischemia. However, cerebral ischemia occurs most frequently in individuals aged Ն65 years. This study examined the protection provided by ischemic preconditioning in a population of aged (18-to 20-month-old) gerbils. Methods-One group of animals was exposed to two 1.5-minute episodes of global ischemia separated by 24 hours and followed 72 hours later by a 5-minute occlusion of both carotid arteries. A second group was given 2 episodes of preconditioning only. Two other groups were exposed to 5 minutes of ischemia or sham surgery. The animals survived 10, 30, or 60 days. Functional and histological assessments were used to determine the extent of protection. Results-Ten days after ischemia there was Ͼ80% protection of CA1 neurons in ischemic preconditioned animals compared with 6% in ischemic gerbils. Nevertheless, these preconditioned animals were impaired in open-field tests of habituation. In addition, CA1 dendritic field potentials were smaller in amplitude compared with those in sham animals. While there was a complete loss of staining for CA1 microtubule-associated protein-2 in ischemic animals, staining in ischemic preconditioned animals was normal. This suggests that dendritic abnormalities per se were not responsible for the observed functional deficits. CA1 cell survival declined to Ϸ75% of sham values (PϽ0.05) at 60 days after ischemia. Conclusions-Ischemic preconditioning provided substantial neuroprotection in aged gerbils. Nonetheless, the striking dissociation between histological and functional protection provided by ischemic preconditioning in aged animals emphasizes the need to use functional end points and long-term survival when assessing neuroprotection. Although functional recovery was evident with increasing survival time, CA1 cell death continued, thereby raising the possibility that the level of neuroprotection attained was not permanent. (Stroke. 1999;30:1240-1246.)