Apoptosis signal-regulating kinase 1 (ASK1) is linked to neural stem cell differentiation after ischemic brain injury

Neural stem cells (NSCs) have been suggested as a groundbreaking solution for stroke patients because they have the potential for self-renewal and differentiation into neurons. The differentiation of NSCs into neurons is integral for increasing the therapeutic efficiency of NSCs during inflammation. Apoptosis signal-regulating kinase 1 (ASK1) is preferentially activated by oxidative stress and inflammation, which is the fundamental pathology of brain damage in stroke. ASK1 may be involved in the early inflammation response after stroke and may be related to the differentiation of NSCs because of the relationship between ASK1 and the p38 mitogen-activated protein kinase pathway. Therefore, we investigated whether ASK1 is linked to the differentiation of NSCs under the context of inflammation. On the basis of the results of a microarray analysis, we performed the following experiments: western blot analysis to confirm ASK1, DCX, MAP2, phospho-p38 expression; fluorescence-activated cell sorting assay to estimate cell death; and immunocytochemistry to visualize and confirm the differentiation of cells in brain tissue. Neurosphere size and cell survival were highly maintained in ASK1-suppressed, lipopolysaccharide (LPS)-treated brains compared with only LPS-treated brains. The number of positive cells for MAP2, a neuronal marker, was lower in the ASK1-suppressed group than in the control group. According to our microarray data, phospho-p38 expression was inversely linked to ASK1 suppression, and our immunohistochemistry data showed that slight upregulation of ASK1 by LPS promoted the differentiation of endogenous, neuronal stem cells into neurons, but highly increased ASK1 levels after cerebral ischemic damage led to high levels of cell death. We conclude that ASK1 is regulated in response to the early inflammation phase and regulates the differentiation of NSCs after inflammatory-inducing events, such as ischemic stroke.

Neuroprotective Effects of Propofol, Ketamine and Propofol-ketamine after Transient Forebrain Ischemia in the Rat / 대한마취과학회지

BACKGROUND: Intravenous anesthetics such as propofol and ketamine have been known to have neuroprotective effects. However, the combination of these drug is not known. This study was conducted to determine the neuroprotective effects of propofol, ketamine or both after transient forebrain ischemia. METHODS: Twenty Sprague-Dawley rats (250-300 gm) were used. Anesthesia was induced with 4% isoflurane in oxygen and then maintained with 1 - 2% isoflurane in oxygen. Ischemic injury was induced by 10 minutes of both common carotid artery ligation and hypotension (MAP < 50 mmHg). All rats were randomly divided into four groups: group I; control group; group II; ketamine 10 mg/kg was administered 10 minutes before injury; group III; propofol (1 mg/kg/min) was administered until EEG isoelectricity; and group IV; ketamine 10 mg/kg and propofol 1 mg/kg/min was administered. The Rectal temperature was maintained at 38oC. After forebrain ischemia, neurologic scores were estimated at 1 hr, 2 hrs, 1 day and 2 days after recovery. The brain was removed 3 days after and stained with H-E stain. RESULTS: Neurologic and histologic scores of group II, III, IV were significantly lower than that of group I. However, there were no significant difference between group II, III and IV. CONCLUSIONS: Ketamine and propofol have neuroprotective effects in transient forebrain ischemia in rats. However, the combination of propofol and ketamine did not show any synergistic or additive effects.