hnRNPA1 SUMOylation promotes cold hypersensitivity in chronic inflammatory pain by stabilizing TRPA1 mRNA.

TRPA1 is pivotal in cold hypersensitivity, but its regulatory mechanisms in inflammatory cold hyperalgesia remain poorly understood. We show here that the upregulation of SUMO1-conjugated protein levels in a complete Freund's adjuvant (CFA)-induced inflammatory pain model enhances TRPA1 mRNA stability, ultimately leading to increased expression levels. We further demonstrate that hnRNPA1 binds to TRPA1 mRNA, and its SUMOylation, upregulated in CFA-induced inflammatory pain, contributes to stabilizing TRPA1 mRNA by accumulating hnRNPA1 in the cytoplasm. Moreover, we find that wild-type hnRNPA1 viral infection in dorsal root ganglia neurons, and not infection with the SUMOylation-deficient hnRNPA1 mutant, can rescue the reduced ability of hnRNPA1-knockdown mice to develop inflammatory cold pain hypersensitivity. These results suggest that hnRNPA1 is a regulator of TRPA1 mRNA stability, the capability of which is enhanced upon SUMO1 conjugation at lysine 3 in response to peripheral inflammation, and the increased expression of TRPA1 in turn underlies the development of chronic inflammatory cold pain hypersensitivity.

Intraarticular Injection of Infliximab-Loaded Thermosensitive Hydrogel Alleviates Pain and Protects Cartilage in Rheumatoid Arthritis.

PURPOSE: Pain and cartilage destruction caused by rheumatoid arthritis (RA) are major challenges during clinical treatment. Traditional systemic administration not only has obvious side effects but also provides limited relief for local symptoms in major joints. Local delivery of therapeutics for RA treatment is a potential strategy but is limited by rapid intraarticular release. MATERIALS AND METHODS: In this study, we prepared a thermoresponsive injectable hydrogel by mixing pluronic F127 (F127) and hyaluronic acid (HA) with poly (γ-glutamic acid) (PGA) incorporating infliximab (IFX), a new generation monoclonal antibody drug. We investigated the biocompatibility of the hydrogel and its IFX release profile. In vivo, we studied the clinical manifestations (articular skin temperature and joint diameter), detected cytokines in the synovial fluid and cartilage, performed behavioral studies on pain relief, and evaluated the cartilage protection effect. RESULTS: A thermoresponsive hydrogel was successfully prepared by mixing F127, HA, and PGA with injectable properties. The F127-HA-PGA hydrogel had a porous structure with interconnected pores. The infliximab-loaded thermosensitive hydrogel exhibited good biocompatibility and biodegradability and sustained release properties. Intraarticular injection of the IFX-loaded F127-HA-PGA hydrogel could alleviate the expression of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-17 (IL-17), in the synovial fluid and cartilage as well as relieve pain and inhibit cartilage destruction in RA. CONCLUSION: The double effect on pain relief and cartilage protection indicated the significant potential of the IFX-loaded injectable hydrogel for RA treatment in major joint lesions.

Depression of Mitochondrial Function in the Rat Skeletal Muscle Model of Myofascial Pain Syndrome Is Through Down-Regulation of the AMPK-PGC-1α-SIRT3 Axis.

PURPOSE: The causative mechanisms triggering myofascial pain syndrome (MPS) are still in debate. It is becoming evident that mitochondrial dysfunction may regulate pathways controlling MPS. The aim of this study was to investigate whether AMPK-PGC-1α-SIRT3 axis is associated with depression of mitochondrial function in the rat MPS model. METHODS: A total of 32 Sprague-Dawley rats were randomly divided into control group and experimental group. The expression level of mRNA and protein of gastrocnemius medialis (GM) was analyzed by Western blot and RT-PCR. The histopathological findings were investigated through electron microscopes in GM of all groups. RESULTS: Our results showed that MPS induces continuous depression of mitochondrial biogenesis and function via down-regulation of PGC-1α-SIRT3 axis accompanying with ATP fuel crisis as compared to control group. However, the expression level of SIRT3 mRNA did not change. Additionally, a correlated reduction of the mRNA and protein expression level of NRF-1 and TFAM, known as the downstream target of PGC-1α, suggesting further transcription of nuclear genes encoding mitochondria functional proteins for promoting mitochondria proliferation, oxidative phosphorylation and energy production is continuously depressed. Furthermore, phosphorylation extent of AMPK is also declined following MPS, and it is negatively correlated with reduction of ATP generation, suggesting that the complex network involves different inhibition in transcription, post-translational modification and a plethora of other effectors that mediate the inhibition roles. CONCLUSION: We here suggested that the down-regulation in AMPK-PGC-1α-SIRT3 axis network may be the basis for the association between mitochondrial dysfunction and MPS, where a vicious circle further aggravates the disease symptoms with ongoing ATP energy crisis.

Association between NMD3 and symptoms of Parkinson's disease in Chinese patients.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that is characterized by motor symptoms such as tremor, rigidity, slowness of movement and problems with gait. Large-scale meta-analyses of genome-wide association studies (GWAS) have identified few susceptibility loci in patients with sporadic PD. The aim of this study was to investigate the association between NMD3 single nucleotide polymorphism (SNP) and symptoms in PD patients in South China. METHODS: A total of 217 PD patients were recruited in this study and genotyped by using the SNaPshot technique and the polymerase chain reaction. All subjects were evaluated by the Mini-Mental State Examination (MMSE), Beijing version Montreal Cognitive Assessment (MoCA), Sniffin' Sticks 16 (SS-16), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, 39-item Parkinson's Disease Questionnaire (PDQ-39) and MDS Unified PD Rating Scale (MDS-UPDRS). RESULTS: NMD3 rs34016896 (C > T) carriers have worse cognitive function than wild types (MMSE: p = 0.042, NMD3 wild type: 27.44 ± 2.89, NMD3 carriers: 26.31 ± 3.79; MoCA: p = 0.005, NMD3 wild type: 23.15 ± 4.20, NMD3 carriers: 20.75 ± 6.68). CONCLUSIONS: The recessive and overdominant model of NMD3 rs34016896 was associated with cognitive impairment in PD patients.

PEAR1 suppresses the proliferation of pulmonary microvascular endothelial cells via PI3K/AKT pathway in ALI model.

BACKGROUND: Activation of the proliferation of pulmonary microvascular endothelial cells (PMVECs) is a key step in the recovery of the integrity of endothelial monolayer, which helps to alleviate acute lung injury (ALI). Platelet endothelial aggregation receptor-1 (PEAR1), expressed on endothelial cells, was reported to inhibit the proliferation of vascular endothelial cells and angiogenesis. However, little is known about its role and mechanism in vascular endothelial disorders in ALI. OBJECTIVE: The aim of this study was to investigate the impact of PEAR1 on the proliferation of pulmonary microvascular endothelial cells in ALI. METHODS: We tested the expression level of PEAR1 in the lungs of WT mice in ALI model induced by intestinal IR. Primary human pulmonary microvascular endothelial cells (HPMECs) were stimulated by 1 mg/L LPS in vitro. We synthesized siPEAR1 and Flag-PEAR1 plasmid to verify the role of PEAR1 on regulating the proliferation of HPMECs under LPS condition and to explore related signaling pathways. RESULTS: The expression level of PEAR1 significantly increased in ALI induced by intestinal IR. PEAR1 knockdown enhanced the proliferation level of HPMECs, which, however, was inhibited by PEAR1 overexpression. PEAR1 knockdown activated PI3K/AKT pathway both in steady state and under LPS condition. PI3K inhibitor, LY294002, reversed the increasing proliferation level and cell progression of HPMECs induced by PEAR1 knockdown after LPS challenge. CONCLUSIONS: PEAR1 acts as a negative regulator in the proliferation of HPMECs in ALI model via the PI3K/AKT pathway.

Impaired B-Cell Maturation Contributes to Reduced B Cell Numbers and Poor Prognosis in Sepsis.

BACKGROUND: Reduced B cell numbers play a critical role in sepsis immunosuppression. The role of B-cell maturation regulated by T follicular helper (Tfh) cells in reduced B cell numbers during sepsis remains unclear. We tested the hypothesis that impaired B-cell maturation contributes to reduced B cell numbers. DESIGN: Retrospective study and observational prospective cohort study. SETTINGS: Critical care units. METHODS: To identify the exact lymphocyte counts that affect the prognosis of sepsis, we first conducted a retrospective study. Then in the prospective cohort study, differences in B-cell maturation, B cell death, and numbers of circulating Tfh (cTfh) cell were compared between 28-day survivors and 28-day non-survivors, mainly by flow cytometry and enzyme-linked immunosorbent assay. MAIN RESULTS: In retrospective study (n = 123), we found patients with lymphocyte counts less than 0.4 × 10 cells/L had higher mortality than patients with lymphocyte counts above 0.4 × 10 cells/L. In observational prospective cohort study (n = 40), compared with survivors, non-survivors had fewer numbers of mature B cell and circulating Tfh (cTfh) cell (sepsis onset: memory B cells: 3.44% vs. 4.48%, antibody-secreting cells: 4.53% vs. 6.30%, cTfh cells: 3.57% vs. 4.49%; 24 h after sepsis onset: memory B cells: 4.05% vs. 7.20%, antibody-secreting cells: 5.25% vs. 8.78%, cTfh cells: 3.98% vs. 6.15%), while there were no differences in cell death of mature B cells between them. We further noticed the numbers of cTfh cell positively correlated with the numbers of mature B cell and immunoglobulin concentrations. CONCLUSIONS: Impaired B-cell maturation contributes to reduced B cell numbers, while the numbers of cTfh cell, acting as a warning indicator for sepsis prognosis, may be a new therapeutic target for treating sepsis.

Salvinorin A moderates postischemic brain injury by preserving endothelial mitochondrial function via AMPK/Mfn2 activation.

Salvinorin A (SA) is a highly selective kappa opioid receptor (KOR) agonist that has significant protective effects on cerebrovascular function after ischemic stroke, but its underlying mechanism is still unclear. This study aimed to investigate whether KOR activation improves the morphology and function of intracellular mitochondria to protect endothelial cells after cerebral ischemia. A transient ischemic brain damage was generated by establishing middle cerebral artery occlusion (MCAO) model in male Sprague-Dawley rats and oxygen glucose deprivation (OGD) model in human brain microvascular endothelial cells (HBMECs). In vivo findings revealed that SA significantly reduced the infarct size, brain edema and Evans blue effusion after MCAO. In vitro findings revealed that SA improved the cell viability and decreased the apoptotic rates in HBMECs OGD model. SA also protected membrane potential and morphology of mitochondria, reduced the ROS level after OGD. SA function was blocked by KOR inhibitor norbinaltorphimine (NB). SA upregulated the phosphorylation levels of AMPK, and Mfn2 expression. Our findings suggest that SA effectively mitigated focal cerebral ischemic injury by activating KOR which potentially preserved mitochondrial function by up-regulating AMPK/Mfn2 in endothelial cells.

Dexmedetomidine pretreatment inhibits cerebral ischemia/reperfusion­induced neuroinflammation via activation of AMPK.

Focal ischemia/reperfusion (I/R) injury induced cerebral inflammation, aggravates brain damage. The aim of the present study was to investigate the protective mechanisms of dexmedetomidine (DEX) on I/R brain injury in rats. Sprague­Dawley rats were divided to seven experimental groups (18 rats/group): Sham surgery; middle cerebral artery occlusion (MCAO) surgery (90 min); DEX10 [10 µg/kg intraperitoneal (i.p.) injection 30 min prior to MCAO]; DEX50 (50 µg/kg i.p. 30 min prior to MCAO); DEX100 (100 µg/kg i.p. 30 min prior to MCAO); DEX50+Yohimbine [YOH; 5 mg/kg 10 min prior to DEX (50 µg/kg i.p.) administration and MCAO] and YOH (5 mg/kg 40 min prior to MCAO). At 24 h post­MCAO surgery, neurological deficit was examined by staining damaged brain tissues with 2,3,5­triphenyltetrazolium chloride. Neuronal apoptosis in the cerebral cortex was histologically assessed by terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling staining, and the expression levels of phosphorylated (p)­AMP­activated protein kinase (AMPK; Thr172) was detected by western blotting. In addition, the expression levels of tumor necrosis factor (TNF)­α and interleukin (IL)­1ß were assessed by ELISA. At days 1, 2 and 5 following I/R, motor functions were assessed by an observer blinded to the study. The brain infarct size, neurological deficit scores, number of apoptotic neurons, expression levels of pro­inflammatory cytokines TNF­α and IL­1ß were increased following MCAO, whereas the motor function scores were reduced. Pretreatment with DEX prior to MCAO can reverse the effects induced by I/R. Compared with rats in the Sham group, the expression levels of p­AMPK were mildly increased in the MCAO group and highly increased in the three DEX­treatment groups. Pretreatment with YOH reversed the above effects of DEX and produced a similar level of cerebral I/R injury. The results demonstrated that precondition with DEX exhibited anti­inflammatory effects on brain ischemic injury mediated by AMPK signal pathway.

Low-dose curcumin stimulates proliferation of rat embryonic neural stem cells through glucocorticoid receptor and STAT3.

AIMS: This study was to determine whether curcumin had any effect on the proliferation of neural stem cell (NSC), analyze the expression of glucocorticoid receptor (GR), signal transducer and activator of transcription 3 (STAT3), and Notch1 at transcription and protein level, and discuss the related mechanisms. METHODS AND RESULTS: NSCs were harvested from E15 SD rat brain and cultured. All experiments were performed at the second passage. Cell cytotoxicity, cell viability, and proliferation assays were used to figure out the optimal concentration of curcumin, which can be used for the protein and mRNA studies. The results showed that by downregulation of GR and STAT3 expression, 0.5 µmol L-1 curcumin exhibited the most pronounced effect in promoting the proliferation of NSCs, which were also induced by antagonists of GR and STAT3, but was inhibited by GR agonist. CONCLUSION: This study shows that low-dose curcumin stimulates the proliferation of NSCs, which is probably by inhibiting the mRNA and protein expressions of GR and directly or indirectly regulating the STAT3 via the synergistic effect of GR and STAT3 pathways and its related signal pathways.

Angiotensin II system in the nucleus tractus solitarii contributes to autonomic dysreflexia in rats with spinal cord injury.

BACKGROUND: Autonomic dysreflexia (AD) is a potentially life-threating complication after spinal cord injury (SCI), characterized by episodic hypertension induced by colon or bladder distension. The objective of this study was to determine the role of impaired baroreflex regulation by the nucleus tractus solitarii(NTS) in the occurrence of AD in a rat model. METHODS: T4 spinal cord transection animal model was used in this study, which included 40 Male rats Colorectal distension (CD) was performed to assess AD and compare the changes of BP, HR, and BRS, six weeks after operation. After that, SCI rats with successfully induced AD were selected. Losartan was microinjected into NTS in SCI rats, then 10, 30, 60 minutes later, CD was performed to calculate the changes of BP, HR, and BRS in order to explicit whether Ang II system was involved in the AD occurrence. Ang II was then Intra-cerebroventricular infused in sham operation rats with CD to mimic the activation of Ang II system in AD. Finally, the level of Ang II in NTS and colocalization of AT1R and NMDA receptor within the NTS neurons were also detected in SCI rats. RESULTS: Compared with sham operation, SCI significantly aggravated the elevation of blood pressure (BP) and impaired baroreflex sensitivity (BRS) induced by colorectal distension; both of which were significantly improved by microinjection of the angiotensin receptor type I (AT1R) antagonist losartan into the NTS. Level of angiotensin II (Ang II) in the NTS was significantly increased in the SCI rats than sham. Intracerebroventricular infusion of Ang II also mimicked changes in BP and BRS induced by colorectal distension. Blockade of baroreflex by sinoaortic denervation prevented beneficial effect of losartan on AD. CONCLUSION: We concluded that the activation of Ang II system in NTS may impair blood pressure baroreflex, and contribute to AD after SCI.

Highly selective non-opioid kappa opioid receptor (KOR) agonist salvinorin A protects against forebrain ischemia-induced brain injury in rats.

OBJECTIVE: To investigate the effect of salvinorin A (SA) on brain injury and neurologic function post-brain ischemia/reperfusion (I/R) using a rat forebrain ischemia model and further explore the effect of kappa opioid receptor (KOR) inhibition by SA on aquaporin-4 (AQP4) expression in the hippocampus, cortex and striatum in the forebrain. METHODS: A forebrain ischemia model was established by colligating the bilateral common carotid arteries of SD rats for 10 min. The rats were randomized to receive dimethyl sulfoxide (DMSO), SA (1 µg/100g body weight) or SA (onset of ischemia) plus SA antagonist nor-BIN (0.2 mg/100g body weight. Rat brain water content was measured. Apoptotic neurons in the hippocampal CA1 region, cortex and striatum were enumerated. AQP4 in CA1, the cortex and the striatum were determined by immunoblotting assays and immunohistochemistry at 24h post-ischemia. Neuromotor tests were performed on day 1, 2 and 5 post-ischemia. Water maze test was carried out on the 5th post-ischemia day. RESULTS: SA significantly attenuated I/R-induced increase in brain water content. Our immunoblotting assays and immunohistochemistry further revealed that SA effectively lessened I/R-induced upregulation of AQP4 expression in the hippocampus, cortex and striatum 24h post-ischemia. SA also significantly reduced the percentage of dead and apoptotic neurons in these regions compared to DMSO. Moreover, SA partially reversed I/R-induced decline in rat motor function and cognition. The neuroprotective effects of SA were partially abolished by nor-BIN. CONCLUSION: SA protects against I/R-induced brain injury by attenuating brain edema formation and inhibiting neuronal death and improves neurologic recovery of rats post-I/R.

Neuroprotective effect of picroside II in brain injury in mice.

Various types of brain injury which led to the damage of brain tissue structure and neurological dysfunction continues to be the major causes of disability and mortality. Picroside II (PII) possesses a wide range of pharmacological effects and has been proved to ameliorate ischemia and reperfusion injury of kidney and brain. However, critical questions remain about other brain injuries. We investigated the protective effect of PII in four well-characterized murine models of brain injury. Models showed a subsequent regional inflammatory response and oxidative stress in common, which might be improved by the administration of PII (20 mg/kg). Meanwhile, a series of morphological and histological analyses for reinforcement was performed. In traumatic, ischemic and infectious induced injuries, it was observed that the survival rate, apoptosis related proteins, Caspase-3, and the expression of acute inflammatory cytokines (IL-1ß, IL-6 and TNF-α) were significantly alleviated after PII injection, but PII treatment alone showed no effect on them as well. The western blot results indicated that TLR4 and NF-κB were clearly downregulated with PII administration. In conclusion, our results suggested that PII with a recommended concentration of 20 mg/kg could provide neuroprotective effects against multi-cerebral injuries in mice by suppressing the over-reactive inflammatory responses and oxidative stress and attenuating the damage of brain tissue for further neurological recovery.

Risk factors of refeeding intolerance in mild acute interstitial pancreatitis: a retrospective study of 323 patients.

OBJECTIVES: This study was aimed to access the frequency and identify independent risk factors of refeeding intolerance in patients with mild acute interstitial pancreatitis. MATERIALS AND METHODS: Patients with mild acute pancreatitis (AP) were included in this observational, descriptive, and retrospective study. Clinical variables, therapy-related variables, and biochemical and radiological variables were analyzed by univariate and multivariate analysis. RESULTS: Of 323 included cases, 40 patients (12.4%) developed refeeding intolerance. In the final regression model, hypertriglyceridemia-induced AP (odds ratio, 7.72; 95% CI: 2.50-23.82, P < 0.001), elevated serum lipase (>2-fold of the upper limit of normal) before refeeding (odds ratio, 2.13; 95% CI: 1.2-3.77, P = 0.009), and immediate feeding (odds ratio, 1.75; 95% CI: 1.31-2.33, P < 0.001) were critical risk factors of refeeding intolerance. CONCLUSION: Refeeding intolerance occurs in 12.4% patients with mild AP and appears more often in those with hypertriglyceridemia-induced AP, elevated serum lipase (>2-fold of the upper limit of normal) before refeeding, and immediate feeding.

Sevoflurane pretreatment enhance HIF-2α expression in mice after renal ischemia/reperfusion injury.

Ischemia/reperfusion (I/R) injury often occurs, which is one of the major causes of acute kidney injury, thus increasing in-hospital mortality. HIF-2α has a protective role against ischemia of the kidney. Renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. We hypothesized that underlying mechanism responsible for renal protection from sevoflurane pretreatment involves the upregulation of HIF-2α. Sevoflurane pretreatment were performed on WT and HIF-2α knockout mice before renal ischemia/reperfusion. Levels of blood urea nitrogen (BUN) and serum creatinine (Cr) were determined with a standard clinical automatic analyzer. The left kidneys were taken for morphological examination. Expression of HIF-2α in kidney tissue was examined by western blotting. In WT mice, group I/R injury had significantly higher BUN and Cr levels than group control, whereas group I/R + Sev had significantly lower BUN and Cr levels than group I/R injury. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. In HIF-2α(-/-) mice, group I/R + Sev showed much higher BUN and Cr levels and severer histological damage than group I/R and group control. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. Our findings suggested that HIF-2α might contribute to the beneficial effect of sevoflurane in renal ischemia/reperfusion injury.

Cost of general anesthesia during radical gastrectomy using different specifications of propofol: cost-minimization analyses.

BACKGROUND: Recently, the economic cost of anesthesiahas attracted attention. To compare the costs of three methods of general anesthesia (GA), a retrospective 1-year study was designed for patients undergoing radical resection for gastric carcinoma. METHODS: A total of 398 patients were originally included in the study. Subjects were divided into three groups according to the mode of anesthesia: balanced anesthesia (BAL; n=258), total intravenous anesthesia (TIVA; n=36), and inhalational anesthesia (INH; n=104). RESULTS: When patients were undergoing elective radical resection for gastric carcinoma, the duration of anesthesia, age, duration of surgery, and postoperative analgesia were positively correlated with the total cost of anesthesia (including wastage of propofol 200 mg:20 mL). Duration of anesthesia and postoperative analgesia were positively correlated with the total cost of anesthesia (including wastage of propofol 500 mg:50 mL). However, the anesthesia group was negatively correlated with the total cost of anesthesia (including drug wastage). When propofol 500 mg:50 mL was used, the total cost of anesthesia and total cost of anesthesia per hour in the BAL group was higher than in the INH group. However, when excluding drug wastage (propofol 200 mg:20 mL), the BAL group was more expensive than the other two groups. CONCLUSION: Use of propofol 200 mg:20 mL as a GA would save money.

The effect of dexmedetomidine post-treatment on the inflammatory response of astrocyte induced by lipopolysaccharide.

To explore the effect of dexmedetomidine (DEX) post-treatment on the inflammatory response of astrocyte induced by lipopolysaccharide (LPS). The astrocytes of neonatal mice were primarily cultured in vitro. After purification and identification, the cells were divided into five groups: group C: control group; group L: astrocytes were treated with 1 µg/ml LPS for 24 h; group D1, D2, and D3: astrocytes were pretreated with 1 µg/ml for 24 h LPS, and then cultured with low (0.1 µM), medium (1 µM), high (10 µM) concentration of DEX for 30 min, respectively. The cell survival rate was detected by cell counting kit. The expressions of inducible nitric oxide synthase (iNOS) mRNA, tumor necrosis gactor-α (TNF-α) mRNA, and interleukin-1ß (IL-1ß) mRNA were measured by RT-PCR in cell lysis solution of every group. The concentration of nitric oxide (NO) was detected by Griess method. The concentrations of IL-1ß and TNF-α were measured, respectively, by enzyme-linked immuno sorbent assay. Compared with the group C, the expressions of iNOS mRNA, TNF-α mRNA, and IL-1ßm RNA were significantly up-regulated, the release of NO, TNF-α, and IL-1ß was significantly increased in group L (P < 0.05). Compared with group L, mRNA levels of inflammation-related factors and release of inflammatory factors were significantly down-regulated in group D2 and D3 (P < 0.05). There was no statistical difference between group D1 and group L. Pre-treatment with medium and high concentration of DEX can inhibit the LPS-induced inflammatory response of astrocyte.

Smaller sized inhaled anesthetics have more potency on senescence-accelerated prone-8 mice compared with senescence-resistant-1 mice.

BACKGROUND: Increasingly more aged people with Alzheimer's disease (AD) must undergo surgery with general anesthesia for various reasons. Knowing the potency of common inhaled anesthetics on AD patients is important to minimize the quantity of inhaled anesthetics. Previous studies indicated that transgenic AD mice were more resistant to the common inhaled anesthetics than were wild-type mice. However, transgenic AD mice are associated with early-onset familial AD, which accounts for only 5% of the total AD patients in the clinic. Confirming the results using other animal AD models is still necessary. OBJECTIVE: The aim of this study was to evaluate the potency of common inhaled anesthetics in another AD animal model, the senescence-accelerated mouse prone-8 (SAMP-8) model. METHODS: The minimum alveolar concentration (MAC) was measured by tail clamping in the SAMP-8 and senescence-resistant-1 (SAMR-1) mice at 4, 6, 8, and 10 months of age (n = 13). A two-way ANOVA (age and strain as the two factors) was used to analyze the difference. RESULTS: The statistical results showed that both the age and strain factors had significant effects on the MAC values. The MAC of the SAMP-8 mice was significantly lower than that of the SAMR-1 mice for the three inhaled anesthetics. The MAC values of the SAMP-8 mice decreased significantly with aging. CONCLUSIONS: The SAMP-8 mice were more sensitive to the three inhaled anesthetics than were the SAMR-1 mice.