- MeSH
- centrální nervový systém * anatomie a histologie diagnostické zobrazování MeSH
- diencefalon anatomie a histologie MeSH
- lidé MeSH
- limbický systém anatomie a histologie MeSH
- mícha anatomie a histologie diagnostické zobrazování MeSH
- mozek anatomie a histologie diagnostické zobrazování krevní zásobení MeSH
- mozkový kmen anatomie a histologie MeSH
- telencefalon anatomie a histologie MeSH
- velký mozek anatomie a histologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Tuberous sclerosis complex (TSC) is a genetic disorder characterized by frequent noncancerous neoplasia in the brain, which can induce a range of severe neuropsychiatric symptoms in humans, resulting from out of control tissue growth. The causative spontaneous loss-of-function mutations have been also identified in rats. Herein, we studied histopathological and molecular changes in brain lesions of the Eker rat model carrying germline mutation of the tsc2 gene, predisposed to multiple neoplasias. Predominant subcortical tumors were analyzed, along with a rare form occurring within the pyriform lobe. The uniform composition of lesions supports the histochemical parity of malformations, with immunofluorescence data supporting their neuro-glial origin. Massive depletion of mature neurons and axonal loss were evident within lesions, with occasional necrotic foci implying advanced stage of pathology. Enrichment of mesenchymal-derived cell markers with hallmarks of neurogenesis and active microglia imply enhanced cell proliferation, with local immune response. The depletion of capillaries within the core was complemented by the formation of dense mesh of nascent vessels at the interface of neoplasia with healthy tissue, implying large-scale vascular remodeling. Taken as a whole, these findings present several novel features of brain tumors in Eker rat model, rendering it suitable for studies of the pathobiology and progression of primary brain tumors, with therapeutic interventions.
- MeSH
- astrocyty patologie MeSH
- axony patologie MeSH
- mikroglie patologie MeSH
- mozek krevní zásobení patologie MeSH
- nádory mozku krevní zásobení etiologie patologie MeSH
- neurony patologie MeSH
- potkani Long-Evans MeSH
- remodelace cév * MeSH
- tuberin genetika MeSH
- tuberózní skleróza komplikace patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Cerebral venous thrombosis is a serious cerebrovascular disease. Due to the variability of clinical symptoms and the scarcity of occurrence, this diagnosis is often delayed. The aim of the study was to describe the risk factors, the initial findings and the imaging methods that lead to the diagnosis. METHODS: We included 34 patients treated for cerebral venous thrombosis in the years 2004-2016. We retrospectively analyzed demographic data, initial clinical symptoms, baseline D-dimer levels, risk factors, time to diagnosis, and MR findings. RESULTS: The most common initial clinical symptom was headache (28 patients, 82.4%). Focal neurological symptoms or signs of encephalopathy developed in 22 patients (64.7%). In 26 patients, we identified at least one risk factor in their history. In women of childbearing potential, 68% of patients (15/22) were taking hormonal contraceptives; in six people the diagnosis was immediately preceded by inflammation. In all patients, the diagnosis was confirmed by MR venography. Positive hereditary thrombophilic conditions were identified in 68% and acquired in 8% of 25 examined patients. In 22 cases, baseline D-dimer levels were examined and found to be increased in 86% of them. The mean time from the first onset of symptoms to diagnosis was 6.9 days. CONCLUSION: Cerebral venous thrombosis has a variable clinical course and the diagnosis is determined a relatively long time after the onset of symptoms. Atypical headache in the patient's history and a set of risk factors are the key findings for indication of imaging methods and confirmation of the diagnosis.
- MeSH
- dospělí MeSH
- intrakraniální trombóza komplikace diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mozek krevní zásobení diagnostické zobrazování MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- žilní trombóza komplikace diagnóza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
To provide basic data on the local differences in density of microvessels between various parts of the human brain, including representative grey and white matter structures of the cerebral hemispheres, the brain stem and the cerebellum, we quantified the numerical density NV and the length density LV of microvessels in two human brains. We aimed to correlate the density of microvessels with previously published data on their preferential orientation (anisotropy). Microvessels were identified using immunohistochemistry for laminin in 32 samples harvested from the following brain regions of two adult individuals: the cortex of the telencephalon supplied by the anterior, middle, and posterior cerebral artery; the basal ganglia (putamen and globus pallidus); the thalamus; the subcortical white matter of the telencephalon; the internal capsule; the pons; the cerebellar cortex; and the cerebellar white matter. NV was calculated from the number of vascular branching points and their valence, which were assessed using the optical disector in 20-μm-thick sections. LV was estimated using counting frames applied to routine sections with randomized cutting planes. After correction for shrinkage, NV in the cerebral cortex was 1311±326mm-3 (mean±SD) and LV was 255±119mm-2. Similarly, in subcortical grey matter (which included the basal ganglia and thalamus), NV was 1350±445mm-3 and LV was 328±117mm-2. The vascular networks of cortical and subcortical grey matter were comparable. Their densities were greater than in the white matter, with NV=222±147mm-3 and LV=160±96mm-2. NV was moderately correlated with LV. In parts of brain with greater NV, blood vessels lacked a preferential orientation. Our data were in agreement with other studies on microvessel density focused on specific brain regions, but showed a greater variability, thus mapping the basic differences among various parts of brain. To facilitate the planning of other studies on brain vascularity and to support the development of computational models of human brain circulation based on real microvascular morphology; stereological data in form of continuous variables are made available as supplements.
BACKGROUND: Neuroanatomic substrates responsible for development of post-stroke spasticity are still poorly understood. The study is focused on identification of brain regions within the territory of the middle cerebral artery associated with spasticity development. METHODS: This is a single-center prospective cohort study of first documented anterior circulation ischemic strokes with a neurologic deficit lasting >7 days (from March 2014 to September 2016, all patients are involved in a registry). Ischemic cerebral lesions within the territory of middle cerebral artery were evaluated using the Alberta Stroke Program Early CT Score (ASPECTS) on control 24-hour computed tomography or magnetic resonance imaging. Spasticity was assessed with modified Ashworth scale. RESULTS: Seventy-six patients (mean age 72 years, 45% females; 30% treated with IV tissue plasminogen activator, 6.5% mechanical thrombectomy) fulfilled the study inclusion criteria. Forty-nine (64%) developed early elbow or wrist flexor spasticity defined as modified Ashworth scale >1 (at day 7-10), in 44 (58%) the spasticity remained present at 6 months. There were no differences between the patients who developed spasticity and those who did not when comparing admission stroke severity (National Institutes of Health Stroke Scale 5 [interquartile range {IQR} 4-8] versus 6 [IQR 4-10]) and vascular risk factors (hypertension, diabetes mellitus, dyslipidemia, atrial fibrillation, coronary artery disease). Nor was there a difference in 24-hour ASPECTS score (9 [IQR 8-10] versus 9 [IQR 7-10]). No differences were found between the groups with and without the early upper limb flexor spasticity of particular regions (M1, M2, M3, M4, M5, M6, lentiform, insula, caudate, internal capsule) and precentral-postcentral gyrus, premotor cortex, supplementary motor area, posterior limb of internal capsule, and thalamus were compared. CONCLUSIONS: We did not find any middle cerebral artery territory associated with post-stroke spasticity development by detailed evaluation of ASPECTS.
- MeSH
- časná diagnóza MeSH
- časové faktory MeSH
- difuzní magnetická rezonance MeSH
- horní končetina inervace MeSH
- infarkt arteria cerebri media komplikace diagnostické zobrazování patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody pro podporu rozhodování * MeSH
- mozek krevní zásobení diagnostické zobrazování MeSH
- mozkový krevní oběh MeSH
- multidetektorová počítačová tomografie * MeSH
- pohybová aktivita MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- prospektivní studie MeSH
- registrace MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- svalová spasticita diagnóza etiologie patofyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. OBJECTIVE: We hypothesize microvascular impairment could be present already in mild cognitive impairment (MCI) and can be revealed using transcranial color-coded sonography (TCCS) and the breath-holding maneuver. METHODS: Three groups of subjects (AD in the stage of dementia, MCI, and cognitively normal controls) with detailed neuropsychological testing and low cerebrovascular burden (no history of stroke, no intra- or extracranial artery stenoses, and no severe vascular lesions on brain MRI), underwent a TCCS assessment of peak systolic (PSV), mean flow (MFV), and end diastolic velocities (EDV) and resistance and pulsatility indices (RI, PI) in large intracranial vessels bilaterally. Cerebrovascular reserve capacity was assessed using the breath-holding index (BHI) in middle cerebral artery (MCA) bilaterally. The ultrasound parameters were compared between the groups, correlated with neuropsychological tests, and compared between amnestic and non-amnestic MCI subtypes. RESULTS: Fourteen AD (3 males, 67.9±11.1 years, MMSE 18.0±4.6), 24 MCI (13 males, 71.9±7.3 years, MMSE 28.0±1.6), and 24 risk factor-matched controls (14 males, 67.8±6.4 years, MMSE 29.1±1.2) were enrolled. Significant differences were found between AD and controls in MFV, EDV, RI, PI in right MCA after breath holding, in PSV, MFV, EDV in left MCA after breath holding, and in BHI on the left side. The left BHI correlated positively with verbal memory test. CONCLUSION: Results show decreased cerebrovascular reserve capacity in AD as a sign of impaired cerebral hemodynamic status without severe underlying atherosclerosis. This can be identified using TCCS and BHI.
- MeSH
- Alzheimerova nemoc diagnostické zobrazování patofyziologie MeSH
- hemodynamika * MeSH
- kognitivní dysfunkce diagnostické zobrazování patofyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek krevní zásobení diagnostické zobrazování patofyziologie MeSH
- mozkový krevní oběh MeSH
- neuropsychologické testy MeSH
- senioři MeSH
- ultrasonografie dopplerovská transkraniální MeSH
- zadržování dechu MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- demence * etiologie MeSH
- diabetes mellitus 2. typu epidemiologie patofyziologie MeSH
- dyslipidemie epidemiologie patofyziologie MeSH
- hodnocení rizik MeSH
- hypertenze epidemiologie patofyziologie MeSH
- ischemie mozku epidemiologie etiologie komplikace MeSH
- lidé MeSH
- mozek krevní zásobení patologie MeSH
- obezita epidemiologie patofyziologie MeSH
- rizikové faktory MeSH
- stárnutí MeSH
- zdravotně rizikové chování MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- aneurysma diagnostické zobrazování epidemiologie patologie MeSH
- cévní mozková příhoda * diagnostické zobrazování etiologie klasifikace komplikace MeSH
- diagnostické techniky neurologické klasifikace MeSH
- dospělí MeSH
- ischemie mozku diagnostické zobrazování etiologie patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek krevní zásobení patologie MeSH
- neurobehaviorální symptomy klasifikace MeSH
- neurochirurgické výkony škodlivé účinky MeSH
- neurologické vyšetření klasifikace metody MeSH
- neuropsychologické testy MeSH
- poruchy osobnosti etiologie MeSH
- subarachnoidální krvácení diagnostické zobrazování epidemiologie komplikace patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Clinical and experimental studies indicate that muscarinic acetylcholine receptors are potential pharmacological targets for the treatment of neurological diseases. Although these receptors have been described in human, bovine and rat cerebral microvascular tissue, a subtype functional characterization in mouse brain endothelium is lacking. Here, we show that all muscarinic acetylcholine receptors (M1-M5) are expressed in mouse brain microvascular endothelial cells. The mRNA expression of M2, M3, and M5 correlates with their respective protein abundance, but a mismatch exists for M1 and M4 mRNA versus protein levels. Acetylcholine activates calcium transients in brain endothelium via muscarinic, but not nicotinic, receptors. Moreover, although M1 and M3 are the most abundant receptors, only a small fraction of M1 is present in the plasma membrane and functions in ACh-induced Ca2+ signaling. Bioinformatic analyses performed on eukaryotic muscarinic receptors demonstrate a high degree of conservation of the orthosteric binding site and a great variability of the allosteric site. In line with previous studies, this result indicates muscarinic acetylcholine receptors as potential pharmacological targets in future translational studies. We argue that research on drug development should especially focus on the allosteric binding sites of the M1 and M3 receptors.
- MeSH
- acetylcholin farmakologie MeSH
- alosterické místo MeSH
- cévní endotel cytologie metabolismus MeSH
- endoteliální buňky účinky léků metabolismus MeSH
- mikrocévy metabolismus MeSH
- mozek krevní zásobení MeSH
- myši inbrední BALB C MeSH
- nikotinové receptory metabolismus MeSH
- receptory muskarinové chemie metabolismus MeSH
- vápníková signalizace účinky léků MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Alteration of the blood-brain barrier (BBB) is a hallmark of tick-borne encephalitis (TBE), a life-threating human viral neuroinfection. However, the mechanism of BBB breakdown during TBE, as well as TBE virus (TBEV) entry into the brain is unclear. Here, primary human microvascular endothelial cells (HBMECs) were infected with TBEV to study interactions with the BBB. Although the number of infected cells was relatively low in culture (<5%), the infection was persistent with high TBEV yields (>10(6)pfu/ml). Infection did not induce any significant changes in the expression of key tight junction proteins or upregulate the expression of cell adhesion molecules, and did not alter the highly organized intercellular junctions between HBMECs. In an in vitro BBB model, the virus crossed the BBB via a transcellular pathway without compromising the integrity of the cell monolayer. The results indicate that HBMECs may support TBEV entry into the brain without altering BBB integrity.
