The supposition of the mechanism of escitalopram makes a dopamine nerve activity rise by inhibiting corticotropinreleasing factor to the non-organic-pain ～A SSRI application is desirable for a non-organic-pain～

Although escitalopram (ESC) is no having dopamine (DA) transporter (DAT) inhibitory-action, having dopamine nerve (A10 nerve) stimulus operation by the ESC used basic experiment is reported. We supposed the mechanism that the DA increases and it supposed the mechanism that makes a non-organic pain disappear with ①5-HT reinforcement of the descending pain modulatory system, ②the opioid receptor activation with the descending pain modulatory system, ③negative emotion block from the amygdala and the hippocampus to the nucleus accumbens, ④5-HT1A receptor stimulation from the activation of the amygdala, ⑤DA-phasic activity activation. As a result ④ and ⑤ two items were an operation with a main restraint mechanism of a nonorganic-pain. ESC is different from other SSRIs, and we know that ESC make a DA increase at the VTA. We supposed amygdala that a functional depression declined by corticotropin-releasing factor (CRF) is improved with ④ and ③. After DA stimulate by A10 nerve, DA is undergone metabolic change to, and the endogenous opioid peptide (βendorphin) is made

Relevance of distinct monocyte subsets to clinical course of ischemic stroke patients.

BACKGROUND AND PURPOSE: The most common strategy for treating patients with acute ischemic stroke is thrombolytic therapy, though only a few patients receive benefits because of the narrow time window. Inflammation occurring in the central nervous system (CNS) in association with ischemia is caused by immune cells including monocytes and involved in lesion expansion. If the specific roles of monocyte subsets in stroke can be revealed, they may become an effective target for new treatment strategies. METHODS: We performed immunological examinations of 36 consecutive ischemic stroke patients within 2 days of onset and compared the results with 24 age-matched patients with degenerative disorders. The stroke patients were repeatedly tested for the proportions of monocyte subsets in blood, and serum levels of pro- and anti-inflammatory cytokines immediately after admission, on days 3-7 and 12-16 after stroke onset, and on the day of discharge. In addition, immunological measurements were analyzed for relationships to stroke subtypes and complications, including progressive infarction (PI) and stroke-associated infection (SAI). RESULTS: Monocyte count was significantly increased from 0-16 days after stroke as compared to the controls (p<0.05). CD14(high)CD16(-) classical and CD14(high)CD16(+) intermediate monocytes were significantly increased from 0-7 and 3-16 days after stroke, respectively (p<0.05), whereas CD14 (dim)CD16(high) non-classical monocytes were decreased from 0-7 days (p<0.05). Cardioembolic infarction was associated with a persistent increase in intermediate monocytes. Furthermore, intermediate monocytes were significantly increased in patients with PI (p<0.05), while non-classical monocytes were decreased in those with SAI (p<0.05). IL-17A levels were positively correlated with monocyte count (r=0.485, p=0.012) as well as the percentage of non-classical monocytes (r=0.423, p=0.028), and negatively with that of classical monocytes (r=-0.51, p=0.007) during days 12-16. CONCLUSIONS: Our findings suggest that CD14(high)CD16(+) intermediate monocytes have a role in CNS tissue damage during acute and subacute phases in ischemic stroke especially in relation to cardioembolism

Time courses of monocyte subsets after stroke.

<p>(<b>A</b>) The overall number of circulating monocytes was increased. The percentages of (<b>B</b>) classical and (<b>C</b>) intermediate Mo were increased, whereas that of (<b>D</b>) non-classical Mo was decreased. Bars show the mean ± SEM. *p<0.05, t-test, compared to control. Control, n=24; day 0-2, n=36; day 3-7, n=35; day 12-16; n=33; day of hospital discharge, n=26.</p

Analysis of monocyte subsets.

<p>(<b>A</b>) Monocytes were gated in a circle using forward scatter (FSC) and side scatter (SSC) plots. (<b>B</b>) Classical monocytes were identified by high expression of CD14 and no expression of CD16 (CD14^highCD16^-), intermediate monocytes by high expression of CD14 and various levels of positivity for the CD16 molecule (CD14^highCD16⁺), and non-classical monocytes by scant expression of CD14 and high expression of CD16 (CD14 ^dimCD16^high). The proportions of each subset were evaluated by comparing the number of cells (dots) in the individual compartment to the total number of monocytes enclosed in the circle designated as P1.</p

Stroke subtypes and intermediate monocytes after hyperacute phase of stroke.

<p>(<b>A</b>–<b>C</b>) A significantly elevated percentage of intermediate Mo in the CE group persisted until the day of discharge. *p<0.05, t-test, as compared to control. C: control; LAA: large artery atherosclerosis; CE: cardioembolism; SAO: small artery occlusion.</p

Dynamics of pro-inflammatory cytokines after stroke.

<p>(<b>A</b>) In the SAI group (closed diamond), serum IL-6 levels were elevated from 0–7 days after stroke, (<b>B</b>) while serum IL-17A levels were elevated in the PI group without SAI (closed square) from 3–7 days after stroke.</p

Stroke subtype and monocyte subsets from day 0-2 (hyperacute phase).

<p>(<b>A</b>) The overall monocyte counts in the LAA and CE groups were significantly increased as compared to the control. (<b>B</b>, <b>C</b>, <b>D</b>) The percentages for the monocyte subsets in the CE group were significantly changed as compared to the control. Bars show the mean ± SEM. *p<0.05, t-test, compared to control. †p<0.05, ANOVA, compared to CE. C: control; LAA: large artery atherosclerosis; CE: cardioembolism; SAO: small artery occlusion.</p

Time courses of monocyte subsets regarding stroke complications.

<p>Classical and intermediate Mo were increased, while non-classical Mo were decreased. Patients were divided into (<b>A</b>) with or without PI, (<b>B</b>) excluding SAI, (<b>C</b>) and with or without SAI. *p<0.05, t test, compared to control. †p<0.05, t test, compared to other group in category. PI = progressing infarction, SAI = stroke-associated infection.</p