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Background: It remains unclear how intracranial pressure (ICP) measures are associated with brain biopsies and radiological markers. Here, we aim to investigate associations between ICP and radiological findings, brain biopsies, and shunt surgery outcome in patients with suspected idiopathic normal pressure hydrocephalus (iNPH)., Method: In this study, we retrospectively analyzed data from 73 patients admitted with suspected iNPH to Kuopio University Hospital. Of these patients, 71% underwent shunt surgery. The NPH registry included data on clinical and radiological examinations, 24-h intraventricular pressure monitoring, and frontal cortical biopsy., Results: The mean ICP and mean ICP pulse wave amplitude were not associated with the shunt response. Aggregations of Alzheimer's disease (AD)-related proteins (amyloid-β, hyperphosphorylated tau) in frontal cortical biopsies were associated with a poor shunt response (P = 0.014). High mean ICP was associated with Evans' index (EI; P = 0.025), disproportional sylvian and suprasylvian subarachnoid spaces (P = 0.014), and focally dilated sulci (P = 0.047). Interestingly, a high pulse wave amplitude was associated with AD-related biopsy findings (P = 0.032), but the mean ICP was not associated with the brain biopsy. The ICP was not associated with medial temporal lobe atrophy, temporal horn widths, or white matter changes. ICP B waves were associated with less atrophy of the medial temporal lobe (P = 0.018) and more severe disproportionality between the sylvian and suprasylvian subarachnoid spaces (P = 0.001)., Conclusions: The EI and disproportional sylvian and suprasylvian subarachnoid spaces were associated with mean ICP. Disproportionality was also associated with ICP B waves. These associations, although rather weak, with elevated ICP in 24-h measurements, support their value in iNPH diagnostics and suggest that these radiological markers are potentially related to the pathogenesis of iNPH. Interestingly, our results suggested that elevated pulse wave amplitude might be associated with brain amyloid accumulation.

Background and Aims: The aim of the present study was to assess soluble CD40 Ligand (sCD40L) levels in relation to impaired glucose tolerance (IGT) at population level., Methods: This study is part of a prospective, population-based cohort study, carried out from 1990 to 2008 in northern Finland. Study members, born in 1935 and living in the City of Oulu, underwent oral glucose tolerance test (OGTT) and measurement of plasma sCD40L at three different time points during the 15-year follow-up. The total number of study members who underwent OGTT was 768 at the baseline, 557 at the first and 467 at the second follow-up. SCD40L levels in patients with IGT were compared with those in subjects with normal glucose tolerance or impaired fasting glucose (non-IGT)., Results: Geometric mean level of sCD40L was significantly higher in the IGT group compared with the non-IGT group at the baseline (0.42 vs. 0.27 ng/mL) and at the first follow-up (1.50 vs. 0.36 ng/mL) (repeated measures mixed models ANOVA, p < 0.05). At the second follow-up (age 72-73 years), however, the difference was not statistically significant (9.44 vs. 7.24 ng/mL). During the entire follow-up, the levels of sCD40L increased significantly both in IGT and non-IGT groups., Conclusion: We found that plasma sCD40L level increases with age as well as there are elevated levels of plasma sCD40L in subjects with IGT compared with non-IGT. This may indicate an increased cardiovascular risk in older age and in subjects with IGT.

Encephalopsin belongs to the family of extraretinal opsins having a putative role in CNS tissue photosensitivity. Encephalopsin mRNA has earlier been localized in rodent brains, but expression and localization of the protein has not yet been reported. In this study, we aimed to define encephalopsin protein abundance and localization in the rodent brain. The distribution and localization of encephalopsin protein in a mouse brain and selected peripheral tissues were analysed in ten mice, using Western blotting and immunohistochemistry. The specificity of immunoreaction was validated by primary antibody omitting and immunizing peptide blocking experiment. We found encephalopsin protein abundant in the mouse brain, but not in the periphery. Encephalopsin protein was present in neurons of the mouse cerebral cortex, paraventricular area, and cerebellar cells. Our results show that encephalopsin is expressed at the protein level in different brain areas of the mouse. Therefore, the suggested idea that encephalopsin plays a role in non-visual photic processes seems to be applicable. Evidently, further investigations are needed to find out the signalling mechanisms, and the potential physiological role of encephalopsin in phototransduction due to the changes in ambient light.

In diabetic patients, proton magnetic resonance spectroscopy (¹H MRS) has revealed increased brain glucose concentration and metabolite alterations that indicate neuronal damage and glial cell activation. Cerebellum is known to be more resistant to hypoglycemia than cerebrum, but the effects of both chronic and acute hyperglycemia on the cerebellum are less well known. ¹H MRS was used to quantify brain glucose and metabolite levels in the cerebellum, cerebral cortex, cerebral white matter, and the thalamus of diabetic and nondiabetic men after an overnight fast and during a hyperglycemic normoinsulinemic clamp with blood glucose 12 mmol/l above baseline. Fasting glucose levels were twice as high in the cerebellum than in the cerebrum. During acute hyperglycemia, the cerebellar glucose concentration increased by 3.0 mmol/l, which equals that in the cortex, but is 35% more than in the thalamus and 173% more than in the white matter. Acute hyperglycemia also increased the cerebellar tissue water content by 10%. There were no differences between diabetic and nondiabetic participants. Notably, the patients with complication free type 1 diabetes showed brain metabolite alterations in the cerebral cortex and the white matter but not in the cerebellum. Our study suggests that diabetes does not alter glucose content or uptake in the cerebellum. The increase in tissue water during acute hyperglycemia may serve to protect the cerebellum from the potentially deleterious effects of the excess glucose.

Acute hyperglycaemia impairs cognitive function. It is however not known, whether different brain regions are equally exposed to glucose during acute hyperglycemia or whether the brain is able to adjust its glucose uptake or metabolism in response to blood glucose fluctuation. We studied the effect of acute hyperglycaemia on the brain glucose concentration in seven men with type 1 diabetes with daily glucose fluctuations of 11 +/- 3 mmol/l, and in eleven age-matched non-diabetic men. Glucose was quantified with proton magnetic resonance spectroscopy in three different brain regions at baseline (fasting glycaemia) and twice during a 2 h hyperglycaemic clamp with plasma glucose increase of 12 mmol/l. The increase in brain glucose during acute hyperglycaemia in the non-diabetic group was: cortex (2.7 +/- 0.9 mmol/l) > thalamus (2.3 +/- 0.7 mmol/l) > white matter (1.7 +/- 0.7 mmol/l, P = 0.021 vs. cortex) and in the diabetic group: cortex (2.0 +/- 0.7 mmol/l) > white matter (1.3 +/- 0.7 mmol/l) > thalamus (1.1 +/- 0.4 mmol/l, P = 0.010 vs. cortex). In the diabetic group, the glucose increase in the thalamus was attenuated compared to the non-diabetic participants (P = 0.011). In conclusion, the increase of glucose during acute hyperglycaemia seems to be dependent on the brain tissue type. The high exposure of cortex to excess glucose and the altered glucose uptake or metabolism in the thalamus may thus contribute to hyperglycaemia related cognitive dysfunction.

Risk factors for the metabolic syndrome (MetS) affect brain function and associate with asymptomatic brain infarctions in healthy individuals. We studied whether MetS risk factors alter cerebral metabolism. Eighteen non-smoking men (36 +/- 6years) were stratified into two groups according to their risk of developing the MetS. Individuals in the Risk group had a family history of type 2 diabetes, were pre-obese, had mild hypertension and higher fasting plasma glucose and serum insulin compared to the Control group with no risk factors. N-acetyl aspartate, choline, total creatine (tCr), myo-inositol, and glucose were studied in the thalamus, frontal cortex, and frontal white matter with proton magnetic resonance spectroscopy. The plasma glucose was 13% higher (p < 0.01) in the Risk group, but the brain glucose levels were comparable between the groups. In the Control group, the thalamic tCr correlated with the thalamic glucose level (r = 0.81, p = 0.015). In the Risk group, the tCr was 17% higher (p = 0.006) and correlated with the fasting plasma glucose concentration (r = 0.78, p = 0.013), but not with the thalamic glucose level. In conclusion, the increased tCr level in the Risk group suggests that a family history of type 2 diabetes together with MetS risk factors alters thalamic energy metabolism.