TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.

BACKGROUND: T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. METHODS: We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression. Twenty-four hours before MCAO, a specific small interfering RNA (siRNA) was introduced. The infarction volume, neurological deficit score and cleaved caspase-3 and Bcl-2 expression were used to assess the effects of TDAG8 on ischaemic stroke. Finally, the effects of TDAG8 on the development of primary cortical neurons exposed to oxygen-glucose deprivation (OGD) were investigated. RESULTS: TDAG8 expression increased both in vivo and in vitro. Pretreatment with BTB09089 up-regulated TDAG8 and Bcl-2 expression and down-regulated cleaved caspase-3 expression, while the infarction volume was reduced, and neurological deficits were ameliorated 24 and 72h after MCAO. However, the protective effects of TDAG8 were reversed when its level was reduced in TDAG8-deficient rats. More importantly, these findings are consistent with data from neurons subjected to OGD. CONCLUSIONS: TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats.

[Association between small dense low-density lipoprotein cholesterol and carotid atherosclerosis].

Objective: To explore the association between small dense low-density lipoprotein cholesterol (sdLDL-C) and carotid atherosclerosis. Methods: 1 578 subjects were enrolled in an annual health check-up program in aerospace center hospital from 2016 to 2017, and these patients were divided into 471 cases (men 343 and women 128) with carotid atherosclerosis (subjects with increased carotid artery intima-media thickness or carotid atherosclerosis plaque) and 1 107 cases (men 567 and women 540) with non- carotid atherosclerosis according to ultrasonography. Serum sdLDL-C levels were measured by peroxidase assay. Results: Serum sdLDL-C was significantly higher in carotid atherosclerosis group (1.11±0.44) mmol/L than that in non-carotid group (0.88±0.40) mmol/L, with significant difference (t=9.856, P<0.001). Stratified by quartiles of sdLDL-C (Q1-Q4), the prevalence of carotid atherosclerosis was significantly increased trend along with increased sdLDL-C levels (P<0.001). In multivariate Logistic regression analysis, after adjustment for age, sex and other traditional atherosclerosis risk factors, comparing Q4 with Q1, the odd ratio of prevalence of carotid atherosclerosis was 5.164, and 95% confidence interval(CI) was 2.833-9.413. While the sdLDL-C threshold was 0.727 mmol/L as the optimal cut-off point, the clinical sensitivity and specificity of sdLDL-C for screening carotid atherosclerosis were 80.5% and 41.4%, respectively. Conclusion: Serum sdLDL-C was an independent risk factor of carotid atherosclerosis. sdLDL-C may be a potentially useful risk marker in early screening for carotid atherosclerosis.

Remifentanil requirements for preventing motor response to skin incision in healthy women anesthetized with combinations of propofol and dexmedetomidine titrated to similar Bispectral Index (BIS) values.

BACKGROUND: It is unclear whether the sedative, analgesic or sympatholytic effects of adjunctive dexmedetomidine contribute to reduced analgesic requirements in general anesthesia. This study aimed to assess the analgesic effect of dexmedetomidine on intraoperative opioid requirements using body movement as observation indicator at similar BIS-guided sedative depth in propofol anesthesia. METHODS: Ninety patients were randomly divided into three groups to receive administration of saline, and dexmedetomidine at 0.5 and 1.0 µg kg(-1) over 10 min, followed by saline and dexmedetomidine at infusion rates of 0.17 and 0.33 µg kg(-1) h(-1), respectively. After dexmedetomidine and saline bolus administration, propofol was titrated to maintain the BIS values at 45-55. When BIS values reached the predetermined range, remifentanil was administered by target-controlled infusion. Five minutes following remifentanil treatment, skin was incised and the motor response observed. Then, the concentration of remifentanil blunting the motor response in 50% of patients (Ce50) was determined using a modified Dixon's sequential 'up-and-down' method. RESULTS: Dexmedetomidine significantly decreased effect-site concentrations of propofol for maintaining the preset BIS range (P < 0.01). The Ce50 (95% CI) of remifentanil were 0.93 (0.82-1.03), 1.03 (0.89-1.17) and 0.91 (0.77-1.06) ng ml(-1) in the 0 (saline), 0.5 and 1.0 µg kg(-1) dexmedetomidine groups, respectively, indicating non-statistically significant differences among groups (P > 0.0167). CONCLUSIONS: Propofol and its combination with dexmedetomidine have similar opioid requirements for preventing motor response to skin incision when titrated to similar BIS values. These findings indicate that adjunctive dexmedetomidine for general anesthesia has sedative but no opioid sparing effects.

Altered responses to cutaneous stimuli in the second somatosensory cortex following lesions of the postcentral gyrus in infant and juvenile macaques.

Infant macaques recover tactile abilities better than older animals after somatosensory cortical lesions. To investigate the neural basis of this phenomenon, we ablated the hand representation in primary somatosensory cortex (SI) of infant and juvenile Macaca mulatta and recorded in ipsilateral second somatosensory cortex (SII) a year later. We also made tracer injections to verify the lesion boundaries and to study the connections of SII after the lesion of SI. Similar to the report of Pons et al. (Science 237:417-420, '87), we found that substantial portions of the SII hand area were unresponsive to cutaneous stimulation of the hand in both age groups. Particularly, there were no cutaneous receptive fields restricted to the digits. Some responses were elicited in each animal by mechanical stimulation of the hand, including a proportion related to cutaneous receptive fields. This proportion was higher in the infants than in the juveniles, which may explain the greater capacity of the infants for recovery of tactile function after SI lesions. The residual somatic drive in the SII hand area of the juveniles was attributable to sparing of parts of areas 3a and 3b. However, in the infants, this explanation was not tenable since the responses noted in SII occurred even after total ablations of the postcentral gyrus. The pattern of corticocortical connections revealed by injections of HRP into the medial margin of the SI lesion and of Fast Blue into SII in one infant confirmed the absence of SI inputs to the region of SII where responses were recorded from the hand. Representations of body parts other than the hand were normally responsive, and their location was consistent with normal somatotopy in SII.