The Neuroprotective Effect of Hemin and the Related Mechanism in Sevoflurane Exposed Neonatal Rats

Abstract

Background Many studies have reported that sevoflurane can increase neuronal apoptosis and result in cognitive deficits in rodents. Although neurotoxicity may be associated with mitochondrial dysfunction and oxidative stress, the exact mechanism remains unclear. In order to evaluate potential treatment therapies, we studied the effects of hemin on neurotoxicity of neonatal rat sevoflurane exposure. Methods Postnatal day (P) seven rats were assigned randomly to four groups; (1) group C: non-anesthesia, (2) group H: intraperitoneal hemin (50 mg kg −1 ) treatment on days 5 and 6, (3) group S: 3% sevoflurane exposure for 4 h, and (4) group SH: hemin treatment + sevoflurane exposure. The expression of neuroglobin in neonatal hippocampus was determined by western blot and immunohistochemistry. Neuroglobin was localized by immunofluorescence. Western blot for the expression of cleaved caspase-3 and TUNEL were used to detect neonatal hippocampal apoptosis, and cytochrome c was used to evaluate mitochondrial function. Drp-1 and Mfn-2 immunoblotting were used to assess mitochondrial dynamics. The Morris water maze test was performed to detect cognitive function in the rats on P30. Results Exposure to sevoflurane increased the expression of cleaved caspase-3, cytochrome c , and Drp1 in the neonatal hippocampus and resulted in cognitive deficiency but decreased expression of Mfn2. Hemin reduced apoptosis, improved mitochondrial dynamics and ameliorated the cognitive impairment caused by sevoflurane exposure. Conclusion Hemin reduced neuronal apoptosis, improved mitochondrial dynamics and protected against cognitive deficits induced by sevoflurane in neonatal rats. This neuroprotective effect may be achieved by increasing the expression of neuroglobin.

Dexmedetomidine Attenuates Neurotoxicity in Developing Rats Induced by Sevoflurane through Upregulating BDNF-TrkB-CREB and Downregulating ProBDNF-P75NRT-RhoA Signaling Pathway

“…Our study found that the hippocampal synaptic protein was still lower when the sevoflurane-inhaled rats reached puberty (32 days of birth) ( Figure 2). This result was consistent with Mediators of Inflammation our previous research and other literature reports [15][16][17][18]. We found that preinjection of dexmedetomidine before sevoflurane exposure can alleviate the decline of long-term hippocampal synaptic protein SYP and PSD95 after sevoflurane anesthesia, suggesting that the protection of dexmedetomidine can last for long term.…”

[Retracted] Involvement of Mitochondrial Dynamics and Mitophagy in Sevoflurane‐Induced Cell Toxicity

“…Following the study of Amrock et al, some researches focus on the expression changes of mitochondrial fission and fusion proteins. These researches found that sevoflurane induces the upregulation of Drp1 and Fis1 and the downregulation of Mfn2 and Opa1 [ 26 , 27 , 40 , 73 ]. It seems that sevoflurane could disturb the balance of mitochondrial dynamics through promoting mitochondrial fission and suppressing mitochondrial fusion, thereby inducing the damage of neural cells.…”

Endogenous Carbon Monoxide Signaling Modulates Mitochondrial Function and Intracellular Glucose Utilization: Impact of the Heme Oxygenase Substrate Hemin

“…Hemin was also recently described to exert neuroprotective effects via abrogation of sevoflurane-induced activation of the mitochondrial intrinsic pathway of apoptosis [40]. This was discussed to be mediated via induction of neuroglobin levels; however, CO signaling following hemin degradation by heme oxygenases was not excluded as the mode of action.…”