Stroke triggers an intense inflammatory response that could be a consequence of Toll-like receptors (TLRs) activation. However, the clinical significance and the therapeutic possibilities of TLR in stroke is not completely clear. In this study, we analyze the association between the expression of TLR2 and TLR4, inflammatory molecules and endogenous ligands, and clinical outcome of ischemic stroke patients, and we test the potential of TLR2/TLR4 and their endogenous ligands as therapeutic targets. For this purpose, we included 110 patients with ischemic stroke finding that TLR2 and TLR4 are independently associated to poor outcome and correlated with higher serum levels of interleukin (IL)1b, IL6, tumor necrosis factor a, and VCAM1, and that TLR4 was independently associated to lesion volume. In addition, we have developed an in vitro model to test the potential therapeutic value of blocking TLR2/TLR4 or their endogenous ligands. Cultured cells (monocytes and human umbilical vein endothelial cells) were treated with serum from ischemic stroke patients, showing a strong inflammatory response that was blocked when TLR2/4 or cellular fibronectin (cFN) or HSP60 were blocked. In conclusion, TLR2 and TLR4 are associated to outcome in stroke patients and TLR2/ 4 or their endogenous ligands, cFN/HSP60 could be new therapeutic targets for ischemic stroke.

Ischaemic stroke is associated with an excessive release of glutamate in brain. GOT (glutamate-oxaloacetate transaminase) and GPT (glutamate-pyruvate transaminase) are two enzymes that are able to metabolize blood glutamate facilitating the lowering of extracellular levels of brain glutamate. Our aim was to study the association between blood levels of both enzymes and stroke outcome in patients with acute ischaemic stroke. We prospectively studied 365 patients with first ischaemic stroke<12 h. Glutamate, GOT and GPT levels were determined in blood samples obtained at admission. We considered functional outcome at 3 months [good outcome: mRS (modified Rankin Scale)≤2; poor outcome mRS >2], END (early neurological deterioration) in the first 72 h [increment ≥4 points in NIHSS (National Institutes of Health Stroke Scale)] and infarct volume [CT (computed tomography) at 36-72 h] as end points. We have found an inverse correlation between GOT and GPT levels and blood glutamate levels. Patients with poor outcome showed lower levels of GOT (11.9±8.2 compared with 22.7±10.2 m-units/ml, P<0.0001) and GPT (19.5±14.3 compared with 24.7±20.3 m-units/ml; P=0.004). A negative correlation has been found between GOT (Pearson coefficient=-0.477, P<0.0001) and GPT (Pearson coefficient=-0.116; P=0.027) levels and infarct volume. Patients with END showed higher levels of blood glutamate (381.7±97.9 compared with 237.6±114.0 μmol/l, P<0.0001) and lower levels of GOT (10.8±6.7 compared with 18.1±10.8 m-units/ml; P<0.0001). This clinical study shows an association between high blood GOT and GPT levels and good outcome in ischaemic stroke patients, this association being stronger for GOT than GPT levels.

Our study showed an increased production of MMP-9 during migraine attacks. These data suggest a possible role of inflammation or blood-brain barrier disruption during the migraine attack.

In experimental models, growth factors (GFs) such as vascular endothelial growth factor (VEGF), Angiopoietin 1 (Ang-1), or granulocyte-colony stimulating factor (G-CSF) mediate brain recovery after intracerebral hemorrhage (ICH). Our aim was to study the association between serum levels of GF and clinical outcome in patients with ICH. A total of 95 patients with primary ICH (male, 66.3%; mean age, 67.8 ± 9.8 years) were prospectively included in the study within 12 h from symptoms onset. The main outcome variable was good functional outcome at 3 months (modified Rankin scale p2). Median serum levels of GF at 72 h from stroke onset were significantly higher in patients with good outcome (n = 39) compared with those with poor outcome (all P < 0.0001). Serum levels of VEGF X330 pg/mL, G-CSF X413 pg/mL, and Ang-1 X35 ng/mL at 72 h were independently associated with good functional outcome (odds ratio (OR), 11.2; 95% confidence interval (CI): 2.9 to 43.0; OR, 19.6; 95% CI: 3.9 to 97.9; and OR, 14.7; 95% CI: 3.6 to 60.0, respectively), neurologic improvement (all P < 0.0001) and reduced residual cavity at 3 months (all P < 0.01). These results illustrate that high serum levels of GF are associated with good functional outcome and reduced lesion volume in ICH.

Chronic periodontitis was independently associated with the presence of LI after adjusting for well-known vascular risk factors for lacunar stroke. Further observational studies are necessary to investigate the pathophysiological mechanisms that can explain this relationship.

Bone marrow-derived stem/progenitor cells (CD34(+) progenitor cells) were demonstrated to play an important role in the regeneration of damaged brain tissue. Our aim was to study the influence of CD34(+) progenitor cells in the outcome of intracerebral hemorrhage (ICH). Thirty-two patients with primary ICH (64.0% male, mean age 67.1 ± 10.8 years) were prospectively included in the study within 12 hr of symptom onset. The main outcome variable was good functional outcome at 3 months (modified Rankin scale ≤ 2). Circulating CD34(+) progenitor cell levels were measured by flow cytometry at admission and at 7 ± 1 days, and serum levels of growth factors (determined by ELISA) were measured at admission and at 24 and 72 hr. Circulating levels of CD34(+) progenitor cells at day 7 were independently associated with good functional outcome at 3 months (OR 1.17, CI95% 1.06-1.39, P = 0.012). On the other hand, CD34(+) progenitor cells at day 7 were negatively correlated with residual cavity volume at 3 months (r = -0.607, P = 0.001). Serum levels of vascular endothelial growth factor (r = 0.386), angiopoietin 1 (r = 0.518), brain-derived neurotrophic factor (r = 0.484), and stromal cell-derived factor-1α (r = 0.837) but not granulocyte-colony stimulating factor (r = -0.038) at 72 hr showed a strong correlation with CD34(+) progenitor cell levels at day 7. These findings suggest that CD34(+) progenitor cells may participate in the functional recovery of ICH patients.

Probiotics have provided benefits to general health, but they are still insufficient to dental health.Objective:This study aimed to evaluate milk supplemented with probiotic bacteria and standard milk, measured by levels of Streptococcus mutans (S. mutans) and Lactobacillus spp., in 3-4-year-old children after 9 months of intervention.Material and Methods:The study was a triple-blind, placebo-controlled, randomized trial. The sample was composed of 363 preschoolers attending five child development centers in Cali, Colombia. They were randomized to two groups: children in the intervention group drank 200 mL of milk with Lactobacillus rhamnosus 5x10 6 and Bifidobacteruim longum 3x10 6 , and children in the control group drank 200 mL of standard milk. Interventions occurred on weekdays and information was gathered through scheduled clinical examination. The primary result was the number of colony forming units (CFU) of S. mutans and Lactobacillus spp. in the saliva. Secondary results were dental caries, rated by the International Caries Detection and Assessment System (ICDAS), dental plaque, pH, and salivary buffer capacity.Results:The proportion of S. mutans was lower in the intervention group compared with the control group after 9 months; however, the differences did not reach statistical significance (p=0.173); on the other hand, statistically significant differences between groups were found in the CFU/mL of Lactobacillus spp. (p=0.002). There was not statistically significant difference in the prevalence of dental caries for both groups (p=0.767). Differences between groups were found in the salivary buffering capacity (p=0.000); neither salivary pH nor dental plaque were significantly different.Conclusions:Regular consumption of milk containing probiotics bacteria reduced CFU/mL of Lactobacillus spp. and increased salivary buffering capacity at 9 months of consumption.

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