Hydrogen atom scattering at the Al2O3(0001) surface: a combined experimental and theoretical study.

Investigating atom-surface interactions is the key to an in-depth understanding of chemical processes at interfaces, which are of central importance in many fields - from heterogeneous catalysis to corrosion. In this work, we present a joint experimental and theoretical effort to gain insights into the atomistic details of hydrogen atom scattering at the α-Al2O3(0001) surface. Surprisingly, this system has been hardly studied to date, although hydrogen atoms as well as α-Al2O3 are omnipresent in catalysis as reactive species and support oxide, respectively. We address this system by performing hydrogen atom beam scattering experiments and molecular dynamics (MD) simulations based on a high-dimensional machine learning potential trained to density functional theory data. Using this combination of methods we are able to probe the properties of the multidimensional potential energy surface governing the scattering process. Specifically, we compare the angular distribution and the kinetic energy loss of the scattered atoms obtained in experiment with a large number of MD trajectories, which, moreover, allow to identify the underlying impact sites at the surface.

A population-based study on dementia and stroke in 97 year olds.

BACKGROUND: the number of nonagenarians increases dramatically worldwide. OBJECTIVES: to examine the prevalence of stroke/transient ischaemic attack (TIA) and dementia, their inter-relationship and their relation to 2-year mortality and institutionalisation in 97 year olds. METHODS: a population-based sample of 97 year olds (n=591) was examined. Information on stroke/TIA was obtained from self-reports, key informants and hospital discharge registers. Dementia was diagnosed according to DSM-III-R criteria. RESULTS: the response rate was 65%. The prevalence of dementia was 32.7% in men and 59.3% in women (P<0.001). The prevalence of stroke/TIA was 21.5% (17.8% in men, 22.3% in women). Stroke/TIA was related to dementia in women (odds ratio=1.9, 95% CI: 1.2-3.0), but not in men. Dementia, but not stroke/TIA, was related to 2-year mortality and institutionalisation in logistic regression models. CONCLUSION: dementia was very common in this age group, and related to mortality and institutionalisation. Stroke/TIA in 97 year olds showed less association with dementia, mortality and institutionalisation than reported in studies of younger elderly populations. The finding that stroke was not associated with dementia in men needs to be taken cautiously due to the small number of men. The findings also emphasise that more studies are needed to scrutinise the aetiology of dementia in nonagenarians.

Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients.

BACKGROUND: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. OBJECTIVE: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. METHODS: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). RESULTS: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. CONCLUSION: This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

Depression as a risk factor for the incidence of first-ever stroke in 85-year-olds.

BACKGROUND AND PURPOSE: Depression may increase the risk for stroke. Few studies have examined whether depression increases the risk for stroke in the very old and among the demented. We examined the relation between depression in 85-year-olds and the 3-year incidence of first-ever stroke. METHODS: A representative sample of 494 85-year-olds (147 demented, 347 nondemented) in Gothenburg, Sweden, was examined with psychiatric examinations and key informant interviews. Diagnoses of depression and dementia were made according to the Diagnostic and Statistical Manual of Mental Disorders, Third Revision. The sample was followed for 3 years regarding the incidence of stroke. Information on stroke was obtained from the Swedish Hospital Discharge Register, death certificates, self-reports, and key informants. Those with known stroke history at baseline (n=93) were excluded from the incidence study. RESULTS: The prevalence of depression at age 85 was 19%. Depression at baseline (hazard ratio, 2.7; 95% CI, 1.5 to 4.7; P=0.0006) and systolic blood pressure (hazard ratio, 1.014 per 1 mm Hg; 95% CI, 1.00 to 1.03; P=0.019) were related to increased incidence of first-ever stroke during follow-up. Depression increased stroke risk both among demented and nondemented individuals. Among the symptoms of depression, only depressed mood was an independent predictor of incidence first-ever stroke in multivariate analyses. Stroke history at age 85 was not associated with clinical depression. CONCLUSIONS: Depression and stroke are both common in elderly populations. The finding that depression increases risk for first-ever stroke indicates that detection and treatment of depression may have implications for stroke prevention.

Influence of the duration of ischemia and reperfusion on infarct volume and microvascular damage in mice.

OBJECTIVES: Focal cerebral ischemia is responsible for alterations of vascular permeability, and the loss of microvascular integrity is a primary source of subsequent hemorrhages. We evaluated the influence of different durations of ischemia and reperfusion on infarction size and microvascular damage after focal cerebral ischemia in the mouse. METHODS: C57BL/6 mice (n=39) were subjected to focal cerebral ischemia (I) and reperfusion (R). Consecutive brain sections were analysed for infarction volumes (Nissl-staining) and for collagen type IV (immunohistochemistry and western blot). RESULTS: Infarction size (percentage of the infarction volume versus ipsilateral hemisphere) increased with total time of ischemia and reperfusion: 19+/-2% (I3R0), 30+/-2% (I3R3), 36+/-4% (I3R12), 41+/-4% (I1R24), 45+/-6% (I2R24) and 58+/-2% (I3R24). The ischemic hemispheres showed a significant progressive reduction of collagen type IV positive vessels (ischemic versus non-ischemic contralateral area): 90+/-3% (I3R0), 88+/-1% (I3R3), 82+/-3% (I3R12), 85+/-3% (I1R24), 79+/-3% (I2R24), 72+/-2% (I3R24). CONCLUSIONS: Both prolonged ischemia and reperfusion lead to an increased infarction volume, as well as progressive microvascular damage.

Matrix metalloproteinase induction by EMMPRIN in experimental focal cerebral ischemia.

Focal cerebral ischemia leads to the gradual disruption of the extracellular matrix. A key role in the turnover of the extracellular matrix is played by the system of matrix metalloproteinases (MMPs). In this study we describe changes of the MMP inducer protein (EMMPRIN) following experimental cerebral ischemia (induced for 3 h and followed by 24 h reperfusion, suture model) in rats. Extracellular EMMPRIN was measured by Western blot of the ischemic and nonischemic basal ganglia and cortex separately. Compared with the contralateral nonischemic area, the ischemic hemisphere showed a significant increase in EMMPRIN: basal ganglia, 158% +/- 4% (P < 0.05); cortex, 128% +/- 25% (P < 0.05). Immunohistochemistry was used to localize EMMPRIN on cerebral microvessels. EMMPRIN-positive microvascular structures were quantified by automatic morphometric video-imaging analysis and a significant increase in the number of cerebral microvessels staining positive for EMMPRIN in the ischemic basal ganglia was shown. The significant loss of microvascular basal lamina antigen collagen type IV in ischemic cortex and basal ganglia was calculated by Western blot. Measured by gelatin zymography, we demonstrated an MMP-2 and MMP-9 increase in the ischemic brain regions (P < 0.05). For the first time the MMP activation system EMMPRIN was shown to be relevant in cerebral ischemia. These results raise the possibility that the increased expression of EMMPRIN, the increase in MMPs and the damage of the basal lamina following cerebral ischemia are connected and part of a network of related changes.

A new approach to reduce the number of animals used in experimental focal cerebral ischemia models.

We describe a novel experimental set-up that allows biochemical, immunohistochemical and morphometric recording of multiple parameters from a single rat brain. The whole brain was cut (coronal sectioning) in a volumetric manner, and 100 cryo-sections (10 microm) were collected from the region of infarction. By use of a scalpel to dissect the cryosection, crude brain material was obtained from the cortical and basal ganglia areas of ischemic and non-ischemic hemispheres. Material from four 10 microm thick sections of the same animal was pooled. About 30 microg protein lysate was extracted per four sections with various lysis buffers; this sufficed for one biochemical or enzymatic test called "micro-Western-blots" or "micro-zymographies". Scraping brain material from cryosections allows the detection of up to 25 parameters from adjacent brain sections of one single rat brain. Different analysis are possible, we have chosen, e.g. to compare factors affecting the basal lamina of cerebral microvessels like the content of the metalloproteinases-2/-9, their tissue inhibitors, the plasminogen activators, collagen type IV, parameters to test the blood-brain barrier: hemoglobin and the protein of the perfusion solution BSA and the infarction volume. On the basis of these parameters it was possible to compare the interactions of the complex processes in the ischemic brain in the same animal in adjacent sections. Thus, this method increases the validity of data comparisons and reduces significantly the number of animals needed in various experimental settings.

Ramipril prevents extracellular matrix accumulation in cerebral microvessels.

OBJECTIVES: The stroke-prone spontaneously hypertensive rat is a genetic model of severe hypertension with secondary vascular alterations. The aim of this study was to determine the influence of chronic hypertension and ramipril treatment on the extracellular matrix in the cerebral microvasculature. METHODS: The study consisted of three groups: six normotensive Wistar rats, six untreated spontaneously hypertensive rats, and six hypertensive rats treated with an antihypertensive dose of ramipril (1 mg kg(-1)day(-1)) for 6 months. Alterations in the extracellular matrix were examined by western blot, immunohistochemistry, and immunofluorescence using an antibody against collagen type IV. RESULTS: Western blotting showed a reduction of the total amount of collagen type IV by 50% in the ramipril group compared with the untreated hypertensive group (51.0+/-9.3% reduction, p = 0.0004). Compared with the untreated hypertensive rats, ramipril treatment prevented a loss of vessel density in the cortex (23.4+/-1.0 versus 20.4+/-2.0, p < 0.0001) and revealed a reduction of the amount of collagen per vessel (0.54+/-0.04 versus 0.60+/-0.08, p = 0.037). The ratio between the vessel wall and the lumen (0.69+/-0.08 versus 1.31+/-0.13) and the relative collagen intensity was lowered in the ramipril group (18.1+/-4.7% reduction, p < 0.0001). Using these methods the ramipril group showed similar results than the normotensive group. DISCUSSION: Ramipril treatment completely prevented these hypertensive vascular changes. These results may stimulate a therapeutic approach with angiotensin converting enzyme inhibition in human hypertensive small vessel disease.

Increasing use of intravenous rt-PA does not affect safety in acute stroke.

BACKGROUND: Intravenous thrombolysis with rt-PA improves outcome in acute ischemic stroke. In a prospective study we analyzed the annual frequency of rt-PA treatment, its safety, and early clinical outcome. METHODS: All patients admitted to our stroke unit (SU) from 1998 to 2003 were registered in a prospective data base. Documented data included patient age, sex, time interval until admission, initial therapy (e. g., thrombolysis), death, intracerebral hemorrhage, other complications, and score on the National Institute of Health Stroke Scale (NIHSS). RESULTS: From 1998 to 2003, a total of 112 patients were treated with systemic thrombolysis. The number of acute stroke patients admitted within 2.5 hours and therefore eligible for thrombolysis did not substantially change between 1998 and 2003. From 1998 to 2001 the percentage of acute stroke patients that received rt-PA was stable (12.6-16.9 %). This percentage increased in 2002 (29.6%, p<0.05) and, again, in 2003 (42.1%, p<0.01). Of all treated patients, two developed symptomatic intracerebral hemorrhage (1.8%) and five died three to seven days after thrombolysis (4.5 %). The NIHSS score of patients receiving rt-PA significantly decreased during the acute treatment phase (14.2+/-5.1 to 8.0+/-5.9, p<0.001). A comparison of single years revealed that this NIHSS score reduction was stable. CONCLUSION: In our selected patients, the proportion of acute stroke patients treated with systemic thrombolysis increased almost three-fold from 1998 to 2003. This may be explained by protocol modifications and growing experience with the use of rt-PA. Our data demonstrate that increased use of rt-PA in acute stroke patients can be achieved without adversely affecting safety or clinical benefit.

Calpain inhibitor A-558693 in experimental focal cerebral ischemia in rats.

OBJECTIVES: Calpains are intracellular proteases, which are activated in various cerebral injuries. We studied the expression of mu-calpain in a model of focal cerebral ischemia/reperfusion and the efficacy of the calpain inhibitor A-558693. METHODS: A transient occlusion of the middle cerebral artery was produced in male Wistar rats by using the suture model with 3 hours of ischemia and 24 hours of reperfusion. Six animals were given the calpain inhibitor and six animals were treated with placebo. The infarct size was determined by the loss of the calpain substrate microtubule-associated protein-2 (MAP-2) immunohistochemistry using volumetry in serial slices of the brains. Furthermore mu-calpain positive-stained cells were detected by immunohistochemistry and western blotting. RESULTS: In placebo-treated animals the mu-calpain expression was significantly increased in the ischemic hemisphere compared with the contralateral non-ischemic hemisphere (88.6 versus 10.5% in the basal ganglia, 60.7 versus 10.7% in the cortex, p < 0.001, respectively) with a subsequent loss its substrate MAP-2. However, the use of the calpain inhibitor A-558693 did not significantly change the mu-calpain expression, nor significantly reduce the infarct volume. DISCUSSION: The present data indicate that mu-calpain proteolysis plays an important role in the chain of events following cerebral ischemia. However, the calpain inhibitor A-558693 failed to prevent these changes.

ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats.

The spontaneously hypertensive stroke-prone rat (SHR-SP) is an experimental model of malignant hypertension which lead to secondary alterations of the extracellular matrix. Our aim was to determine ACE-inhibitor related changes of proteases involved in the reconstruction of the extracellular matrix in the brain. Twelve SHR-SP rats were randomized into two groups. Each group was treated with either an antihypertensive dose of ramipril or placebo for 6 months. Brain tissue plasminogen activator (t-PA) and urokinase (u-PA) were quantified by using casein-dependent plasminogen zymography, matrix metalloproteinase (MMP)-2 and MMP-9, by MMP-zymography, and tissue inhibitor of MMP (TIMP)-1 and -2, by reverse zymography. The amounts of u-PA, t-PA, and MMPs were significantly reduced in animals treated with ACE inhibitor. Plasminogen zymography showed a 39% reduction of u-PA in the basal ganglia (p < 0.0001); t-PA expression was reduced by 26% in the cortex and by 33% in the basal ganglia (p < 0.0001). MMP-2 expression was reduced by 15% in the cortex (p < 0.05) and by 10% in the basal ganglia (p < 0.05); MMP-9 expression significantly decreased by 37% in the cortex and by 25% in the basal ganglia (p < 0.0001 each). No differences were observed in the amount of TIMP-1 or TIMP-2. These findings provide new insights into the biochemical mechanisms underlying extracellular matrix proliferation and its modulation by ACE inhibitors. Therapeutic alterations that influence the proteolytic systems might prove important in the prevention of extracellular matrix accumulation and secondary microvascular vessel wall changes.

Aging is associated with increased collagen type IV accumulation in the basal lamina of human cerebral microvessels.

BACKGROUND: Microvascular alterations contribute to the development of stroke and vascular dementia. The goal of this study was to evaluate age and hypertension related changes of the basal lamina in cerebral microvessels of individuals, who died from non-cerebral causes. RESULTS: We examined 27 human brains: 11 young and 16 old patients. Old patients were divided into two subgroups, those with hypertension (n = 8) and those without hypertension (n = 8). Basal lamina changes of the cerebral microvessels were determined in the putamen using antibodies against collagen type IV and by quantitative analysis of vessel number, total stained area of collagen, thickness of the vessel wall and lumen, and relative staining intensity using immunofluorescence. The total number of collagen positive vessels per microscopic field was reduced in old compared to young subjects (12.0+/-0.6 vs. 15.1+/-1.2, p = 0.02). The relative collagen content per vessel (1.01+/-0.06 vs. 0.76+/-0.05, p = 0.01) and the relative collagen intensity (233.1+/-4.5 vs. 167.8+/-10.6, p < 0.0001) shown by immunofluorescence were higher in the older compared to the younger patients with a consecutive reduction of the lumen / wall ratio (1.29+/-0.05 vs. 3.29+/-0.15, p < 0.0001). No differences were observed for these parameters between old hypertensive and non-hypertensive patients. CONCLUSIONS: The present data show age-related changes of the cerebral microvessels in sections of human putamen for the first time. Due to the accumulation of collagen, microvessels thicken and show a reduction in their lumen. Besides this, the number of vessels decreases. These findings might represent a precondition for the development of vascular cognitive impairment. However, hypertension was not proven to modulate these changes.

Silent and symptomatic infarcts on cranial computerized tomography in relation to dementia and mortality: a population-based study in 85-year-old subjects.

BACKGROUND AND PURPOSE: Incidental findings of infarcts on brain imaging are common, but their clinical significance is not clear. We examined the prevalence of symptomatic and silent infarcts on cranial computerized tomography (cCT) and their relation to dementia and mortality in a representative sample of 239 85-year-olds living in Gothenburg Sweden. METHODS: Information on stroke was obtained from an inpatient hospital linkage system, self-reports, and key informants. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd revision. Cortical and lacunar infarcts were diagnosed on cCT. RESULTS: The prevalence of cerebral infarcts was 17.1%, and half of those were clinically silent (8.6%). The frequency of dementia was increased in those with symptomatic (OR, 5.5; 95% CI, 2.1 to 14.1) and silent infarcts (OR, 2.7; 95% CI, 1.1 to 6.7). Infarcts increased the risk for dementia and its severity in women but not in men. The 3-year mortality rate was increased in those with symptomatic (OR, 4.0; 95% CI, 1.6 to 9.6) and silent infarcts (OR, 3.4; 95% CI, 1.4 to 8.5). CONCLUSIONS: Almost one fifth of 85-year-olds have infarcts on cCT, and half of those are clinically silent. These infarcts are related to an increased rate of dementia and 3-year mortality. Cerebrovascular disease as a cause of dementia may be underrated because of silent infarcts. It has to be elucidated whether treatment of risk factors for stroke may reduce the consequences of silent infarcts.

Delayed moderate hypothermia reduces calpain activity and breakdown of its substrate in experimental focal cerebral ischemia in rats.

Calpains, intracellular proteases, are involved in various cerebral disorders. To determine the effect of moderate hypothermia on calpain activity, transient middle cerebral artery occlusion in rats was performed. For the reperfusion period normothermic temperature was compared to post-ischemic hypothermia (32 degrees C). Calpain expression was measured by Western blot analysis and immunohistochemistry. The loss of calpain substrate was determined by immunohistochemistry against the anti-microtubule-associated protein-2 (MAP-2). The increase of calpains in the ischemic as compared to the non-ischemic contralateral hemisphere and the loss of MAP-2 were reduced by hypothermia. These data indicate that calpain activity and calpain-induced proteolysis play an important role in the network of events following cerebral ischemia and can be reduced by hypothermia. Moderate hypothermia may be a useful tool to limit secondary injury induced by intracellular calpain degradation.

Mild to moderate hypothermia prevents microvascular basal lamina antigen loss in experimental focal cerebral ischemia.

BACKGROUND AND PURPOSE: Microvascular basal lamina damage occurs after cerebral ischemia and is important for the development of hemorrhage. The aim of this study was to determine whether hypothermia could maintain microvascular integrity in ischemic stroke. METHODS: Using the suture model, we subjected 12 rats to 3 hours of focal ischemia and 24 hours of reperfusion. Six rats received postischemic normothermia (37 degrees C) and 6 received hypothermia (32 degrees C to 34 degrees C) for the reperfusion period; a group of 6 sham-operated animals without ischemia was used as control. Collagen type IV and hemoglobin were measured by Western blot analysis, matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography, and urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) by plasminogen-casein zymography. RESULTS: Hypothermia reduced basal lamina collagen type IV loss: 87+/-16% (hypothermia) versus 43+/-4% (normothermia) in basal ganglia and 74+/-16% versus 64+/-4% in cortex; hypothermia reduced hemorrhage from 431+/-65% (normothermia) to 241+/-28% (basal ganglia) (P<0.05). Hypothermia also reduced MMP-2, MMP-9, uPA, and tPA (basal ganglia: MMP-2: 71+/-20% [hypothermia] versus 109+/-3% [normothermia]; MMP-9: 38+/-12% versus 115+/-4%; uPA activity: 310+/-86% versus 1019+/-22%; tPA activity: 61+/-17% versus 111+/-13%; cortex: MMP-2: 53+/-6% versus 116+/-1%; MMP-9: 16+/-4% versus 123+/-3%; uPA: 180+/-27% versus 176+/-10%; tPA: 91+/-15% versus 101+/-8%; each difference: P<0.001) (nonischemic control side=100%). CONCLUSIONS: Hypothermia maintains microvascular integrity and reduces hemorrhage and the activities of MMP-2, MMP-9, uPA, and tPA.

Microvascular Basal lamina damage after embolic stroke in the rat: relationship to cerebral blood flow.

Microvascular basal lamina damage has been demonstrated after balloon occlusion of the middle cerebral artery in the nonhuman primate and after intravascular filament occlusion in the rat. The aim of the present study was to investigate in the rat whether microvascular damage can be found in the stroke model of intracarotid clot injection as early as 3 hours after clot injection and whether microvascular damage relates to the level of regional cerebral blood flow (rCBF). Microvascular densities and total stained microvascular areas were determined by immunohistochemistry of collagen type IV in cortex and basal ganglia and automatic video-imaging analysis. rCBF was measured by autoradiography in the same brain areas. Compared with the corresponding areas in the nonischemic hemisphere, a significant loss of microvascular density (-16%) and total stained microvascular areas (-10%) was observed in these areas. The reduction of microvascular basal lamina staining was comparable in all animals and was not related to the value of rCBF when measured 3 hours after onset of embolic stroke. In conclusion, microvascular damage occurs as soon as 3 hours after intracarotid clot injection, even in brain areas in which rCBF has returned to normal values.

Stroke in 85-year-olds: prevalence, incidence, risk factors, and relation to mortality and dementia.

BACKGROUND AND PURPOSE: Stroke and dementia are major health problems in the elderly. We examined the prevalence and incidence of stroke and their relation to dementia in a representative sample of 494 subjects 85 years of age from Gothenburg, Sweden, who were followed up to 88 years of age. METHODS: Information on stroke was obtained from an inpatient hospital linkage system, death certificates, self-reports, and key informants. Dementia was defined according to the Diagnostic and Statistical Manual of Mental Disorders, third revision. RESULTS: The prevalence of stroke at 85 years of age was 18.8% (self-reports, 10.7%; key informants, 13.2%; register data, 13.0%). The incidence of stroke between 85 and 88 years of age was 57.2/1000 person-years (men, 32.5/1000 person-years; women. 66.9/1000 person-years; self-reported, 30.8/1000 person-years; key informants, 38.5/1000 person-years; register data, 45.4/1000 person-years). Female sex (risk ratio [RR], 2.1; 95% confidence interval [CI], 1.0 to 4.8) and higher systolic blood pressure (per 10 mm Hg: RR, 1.14; 95% CI, 1.02 to 1.28) were associated with higher incidence of stroke. Baseline stroke was related to increased mortality in women and higher prevalence but not incidence of dementia. There was an association between incidence strokes and incidence dementia between 85 and 88 years of age (RR, 3.8; 95% CI, 2.2 to 6.7). CONCLUSIONS: One fifth of 85-year-olds had stroke, and half of those were demented. In this age, it is important to use several sources of information to detect stroke because of the high number of demented. High blood pressure increases stroke risk also in the very old, which is important in relation to prevention.

Increased calpain expression following experimental cerebral venous thrombosis in rats.

INTRODUCTION: Calpains are intracellular proteases that are activated by increased intracellular calcium with proteolytic activity mainly against the cytoskeleton. We tested the expression of calpains and their substrates in an animal model of experimental cerebral venous thrombosis. MATERIALS AND METHODS: Cerebral venous thrombosis was induced in seven male rats by rostral and caudal ligation of the superior sagittal sinus and injection of a thrombogenic cephalin suspension. Each animal survived 3 h of thrombosis. Using a polyclonal antibody against the 80 kD subunit of micro-calpain, immunohistochemistry of the region of interest (venous infarction) showed a loss of microtubule-associated protein-2. The micro-calpain-positive cells in the region of interest and normal tissue were measured using a video-imaging microscopy unit with magnification power of 400x. A cell was considered calpain positive when the nucleus and the periplasma were stained by the micro-calpain antibody. RESULTS: The mean infarct size was 13.4+/-3.7% of one whole coronal section. A total of 57+/-14% of the cells were found to be calpain positive in the region of interest, whereas 5+/-2% of all cellular elements in unaffected tissue were calpain positive (p<0.001). CONCLUSIONS: In conclusion, cerebral venous thrombosis causes an increase in calpain expression in affected tissue which is manifested by a loss of microtubule-associated protein-2. This increase might mediate secondary neuronal injury.