Bartosz Karaszewski

The relationship between stroke severity (NIHSS) and lactate in brain sub-regions in acute ischemic stroke.

Cerebrolysin (Cere) is a compound with neurotrophic activity shown to be effective in Alzheimers disease in earlier trials. The efficacy and safety of three dosages of Cere were investigated in this randomized, double‐blind, placebo‐controlled, study. Two hundred and seventy‐nine patients were enrolled (69 Cere 10 ml; 70 Cere 30 ml; 71 Cere 60 ml and 69 placebo). Patients received iv infusions of 10, 30, 60 ml Cere or placebo 5 days/week for the first 4 weeks and thereafter, two iv infusions per week for 8 weeks. Effects on cognition and clinical global impressions were evaluated 4, 12 and 24 weeks after the beginning of the infusions using the CIBIC+ and the modified Alzheimers Disease Assessment Scale (ADAS)‐cog. At week 24, significant improvement of cognitive performance on the ADAS‐cog (P = 0.038) and global function (CIBIC+; P > 0.001) was observed for the 10 ml dose. The 30 and 60 ml doses showed significant improvement of the global outcome but failed to show significant improvement of cognition. The results are consistent with a reversed U‐shaped dose–response relationship for Cere. The percentage of patients reporting adverse events was similar across all study groups. Cere treatment was well tolerated and led to significant, dose‐dependent improvement of cognition and global clinical impression.

Measurement of brain temperature with magnetic resonance spectroscopy in acute ischemic stroke.

Pyrexia is associated with poor outcome after stroke, but the temperature changes in the brain after stroke are poorly understood. We used magnetic resonance spectroscopic imaging (water‐to‐N‐acetylaspartate frequency shift) to measure cerebral temperature noninvasively in stroke patients.

Improving the resolution of neuropeptides in rat brain with on-line HILIC-RP compared to on-line SCX-RP.

Our two already established on-line 2-D LC systems, a strong cation exchange-RP chromatography (SCX-RP) system and a hydrophilic interaction LC (HILIC)-RP 2-D LC system, were compared to explore which system is best suited for our further studies of differences in cerebral neuropeptide expression as a function of hypoxia-caused stress. The same mass spectrometer and database search parameters were applied in both systems. In total, 19 first dimension fractions were collected with the novel on-line HILIC-RP system, including a Hypercarb SPE column that was applied to trap the compounds not retained on a Kromasil C18 enrichment column. In contrast, six fractions were collected in the SCX-RP method, due to practical limitations of this traditional on-line 2-D LC system. With the on-line HILIC-RP system three times more peaks were detected. It was observed that most of the compounds eluted in the first two fractions in the SCX-RP method, while in the 2-D HILIC-RP method there seemed to be no correlation between peaks detected and fraction number. Thus, from this systematic study it seems that on-line HILIC-RP chromatography is the method of choice for comparative peptidomics of cerebral neuropeptides in future studies.

Relationships Between Brain and Body Temperature, Clinical and Imaging Outcomes after Ischemic Stroke

Pyrexia soon after stroke is associated with severe stroke and poor functional outcome. Few studies have assessed brain temperature after stroke in patients, so little is known of its associations with body temperature, stroke severity, or outcome. We measured temperatures in ischemic and normal-appearing brain using 1 H-magnetic resonance spectroscopy and its correlations with body (tympanic) temperature measured four-hourly, infarct growth by 5 days, early neurologic (National Institute of Health Stroke Scale, NIHSS) and late functional outcome (death or dependency). Among 40 patients (mean age 73 years, median NIHSS 7, imaged at median 17 hours), temperature in ischemic brain was higher than in normal-appearing brain on admission (38.6°C-core, 37.9°C-contralateral hemisphere, P = 0.03) but both were equally elevated by 5 days;both were higher than tympanic temperature. Ischemic lesion temperature was not associated with NIHSS or 3-month functional outcome;in contrast, higher contralateral normal-appearing brain temperature was associated with worse NIHSS, infarct expansion and poor functional outcome, similar to associations for tympanic temperature. We conclude that brain temperature is higher than body temperature;that elevated temperature in ischemic brain reflects a local tissue response to ischemia, whereas pyrexia reflects the systemic response to stroke, occurs later, and is associated with adverse outcomes.

Brain choline concentration Early quantitative marker of ischemia and infarct expansion

Objective: Better prediction of tissue prognosis in acute stroke might improve treatment decisions. We hypothesized that there are metabolic ischemic disturbances measurable noninvasively by proton magnetic resonance spectroscopy (1H MRS) that occur earlier than any structural changes visible on diffusion-tensor imaging (DTI), which may therefore serve for territorial identification of tissue at risk. Methods: We performed multivoxel 1H MRS plus DTI within a maximum of 26 hours, and DTI at 3–7 days, after ischemic stroke. We compared choline, lactate, N-acetylaspartate, and creatine concentrations in normal-appearing voxels that became infarcted (infarct expansion) with normal-appearing voxels around the infarct that remained “healthy” (nonexpansion) on follow-up DTI. Each infarct expansion voxel was additionally classified as either complete infarct expansion (infarcted tissue on follow-up DTI covered ≥50% of the voxel) or partial infarct expansion (<50% of voxel). Results: In 31 patients (NIH Stroke Scale score 0–28), there were 108 infarct nonexpansion voxels and 113 infarct expansion voxels (of which 80 were complete expansion and 33 partial expansion voxels). Brain choline concentration increased for each change in expansion category from nonexpansion, via partial expansion to complete expansion (2,423, 3,843, 4,158 IU; p < 0.05). Changes in lactate, N-acetylaspartate, and creatine concentrations in expansion category were insignificant although for lactate there was a tendency to such association. Conclusions: Choline concentration measurable with 1H MRS was elevated in peri-ischemic normal-appearing brain that became infarcted by 3–7 days. The degree of elevation was associated with the amount of infarct expansion. 1H MRS might identify DTI-normal-appearing tissue at risk of conversion to infarction in early stroke.

Temporal profile of body temperature in acute ischemic stroke: relation to stroke severity and outcome

BackgroundPyrexia after stroke (temperature ≥37.5°C) is associated with poor prognosis, but information on timing of body temperature changes and relationship to stroke severity and subtypes varies.MethodsWe recruited patients with acute ischemic stroke, measured stroke severity, stroke subtype and recorded four-hourly tympanic (body) temperature readings from admission to 120 hours after stroke. We sought causes of pyrexia and measured functional outcome at 90 days. We systematically summarised all relevant previous studies.ResultsAmongst 44 patients (21 males, mean age 72 years SD 11) with median National Institute of Health Stroke Score (NIHSS) 7 (range 0–28), 14 had total anterior circulation strokes (TACS). On admission all patients, both TACS and non-TACS, were normothermic (median 36.3°C vs 36.5°C, p=0.382 respectively) at median 4 hours (interquartile range, IQR, 2–8) after stroke; admission temperature and NIHSS were not associated (r2=0.0, p=0.353). Peak temperature, occurring at 35.5 (IQR 19.0 to 53.8) hours after stroke, was higher in TACS (37.7°C) than non-TACS (37.1°C, p<0.001) and was associated with admission NIHSS (r2=0.20, p=0.002). Poor outcome (modified Rankin Scale ≥3) at 90 days was associated with higher admission (36.6°C vs. 36.2°C p=0.031) and peak (37.4°C vs. 37.0°C, p=0.016) temperatures. Sixteen (36%) patients became pyrexial, in seven (44%) of whom we found no cause other than the stroke.ConclusionsNormothermia is usual within the first 4 hours of stroke. Peak temperature occurs at 1.5 to 2 days after stroke, and is related to stroke severity/subtype and more closely associated with poor outcome than admission temperature. Temperature-outcome associations after stroke are complex, but normothermia on admission should not preclude randomisation of patients into trials of therapeutic hypothermia.

Do acute phase markers explain body temperature and brain temperature after ischemic stroke

Objective: Both brain and body temperature rise after stroke but the cause of each is uncertain. We investigated the relationship between circulating markers of inflammation with brain and body temperature after stroke. Methods: We recruited patients with acute ischemic stroke and measured brain temperature at hospital admission and 5 days after stroke with multivoxel magnetic resonance spectroscopic imaging in normal brain and the acute ischemic lesion (defined by diffusion-weighted imaging [DWI]). We measured body temperature with digital aural thermometers 4-hourly and drew blood daily to measure interleukin-6, C-reactive protein, and fibrinogen, for 5 days after stroke. Results: In 44 stroke patients, the mean temperature in DWI-ischemic brain soon after admission was 38.4°C (95% confidence interval [CI] 38.2–38.6), in DWI-normal brain was 37.7°C (95% CI 37.6–37.7), and mean body temperature was 36.6°C (95% CI 36.3–37.0). Higher mean levels of interleukin-6, C-reactive protein, and fibrinogen were associated with higher temperature in DWI-normal brain at admission and 5 days, and higher overall mean body temperature, but only with higher temperature in DWI-ischemic brain on admission. Conclusions: Systemic inflammation after stroke is associated with elevated temperature in normal brain and the body but not with later ischemic brain temperature. Elevated brain temperature is a potential mechanism for the poorer outcome observed in stroke patients with higher levels of circulating inflammatory markers.

Two-dimensional LC-MS/MS in detection of peptides in hypothalamus of the rat subjected to hypoxic stress

A capillary 2-D LC method coupled with IT MS has been used for separation and identification of peptides in rat hypothalamus. Animals of two different age groups (8 and 50 wk) were exposed to two different rates of CO(2 )in inhaled air to investigate the influence of different hypoxia/hypercapnia levels and their stress-related factor on the peptide excretion. Peptide compounds were fractionated (strong cation exchange chromatography), trapped, and separated (RP chromatography), and MS/MS mass spectra were used for identification. About 107 peptide compounds were identified and 88 of them were semiquantified. Among the characterized peptides, there were fragments from proteins such as proenkephalin A, proSAAS, prosomatostatin, prooxytocin, vasopressin, etc. Explorative principal component analysis (PCA) combined with hypothesis testing was applied to the obtained data to investigate the impact of age and hypoxic stress factors on the peptide pattern. Twenty-six peptides revealed significant differences in concentrations between the animal groups influenced by age and influx rate.

High magnesium or potassium hair accumulation is not associated with ischemic stroke risk reduction: A pilot study

OBJECTIVES Various studies suggest that deficiency of magnesium and potassium may be associated with increased risk of ischemic stroke. However, single time-point serum measurements may not be suitable for assessing long-term tissue levels. PATIENTS AND METHODS We investigated Mg and K levels in hair of patients with acute ischemic stroke. The elements hair accumulation analysis might provide historical information on their concentrations over a longer period of time and probably reflects the corresponding nutritional condition. The concentrations of Mg and K in hair of 48 men with acute ischemic stroke and a control group were measured using spectroscopic methods. RESULTS The mean Mg and K concentrations in hair of patients were significantly higher than in the controls. CONCLUSIONS This analysis does not seem to confirm the results of the previous studies suggesting that Mg or K high levels (or their diet supplementation) might protect humans against ischemic stroke.

A chamber for testing the release of volatile substances secreted by animals, especially mammals, as exemplified by substances released by rats in response to stress

Abstract The success of the testing of volatile organic compounds emitted by animals is dependent on the creation of appropriate conditions for air sampling subsequently used to assay and identify the compounds. These conditions play a particularly important role in the investigation of pheromones, which are secreted in extremely low concentrations. The authors have not come across any previous work which offers constructional solutions, which would allow avoidance of contamination of the air samples containing volatile substances secreted by animals. A constructional solution was developed, which provides optimal conditions for their sampling and isolation. Its main advantages are as follows: the exposure chamber (the chamber in which the animal is studied) is filled with synthetic air; the exposure chamber is separated from the atmospheric air with a synthetic air “jacket”; the exposure chamber has been constructed using materials which do not release chemicals and absorb them in trace quantities.