- Where are we? The anatomy of the murine cortical meninges revisited for intravital imaging, immunology, and clearance of waste from the brain. [Review]
- PNProg Neurobiol 2017; 156:107-148
- Rapid progress is being made in understanding the roles of the cerebral meninges in the maintenance of normal brain function, in immune surveillance, and as a site of disease. Most basic research on …
Rapid progress is being made in understanding the roles of the cerebral meninges in the maintenance of normal brain function, in immune surveillance, and as a site of disease. Most basic research on the meninges and the neural brain is now done on mice, major attractions being the availability of reporter mice with fluorescent cells, and of a huge range of antibodies useful for immunocytochemistry and the characterization of isolated cells. In addition, two-photon microscopy through the unperforated calvaria allows intravital imaging of the undisturbed meninges with sub-micron resolution. The anatomy of the dorsal meninges of the mouse (and, indeed, of all mammals) differs considerably from that shown in many published diagrams: over cortical convexities, the outer layer, the dura, is usually thicker than the inner layer, the leptomeninx, and both layers are richly vascularized and innervated, and communicate with the lymphatic system. A membrane barrier separates them and, in disease, inflammation can be localized to one layer or the other, so experimentalists must be able to identify the compartment they are studying. Here, we present current knowledge of the functional anatomy of the meninges, particularly as it appears in intravital imaging, and review their role as a gateway between the brain, blood, and lymphatics, drawing on information that is scattered among works on different pathologies.
- The mouse cortical meninges are the site of immune responses to many different pathogens, and are accessible to intravital imaging. [Review]
- MMethods 2017 08 15; 127:53-61
- A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation…
A wide range of viral and microbial infections are known to cause meningitis, and there is evidence that the meninges are the gateway to pathogenic invasion of the brain parenchyma. Hence observation of these regions has wide application to understanding host-pathogen interactions. Interactions between pathogens and cells of the immune response can be modified by changes in their environment, such as suppression of the flow of blood and lymph, and, particularly in the case of the meninges, with their unsupported membranes, invasive dissection can alter the tissue architecture. For these reasons, intravital imaging through the unperforated skull is the method of choice. We give a protocol for a simple method of two-photon microscopy through the thinned cortical skull of the anesthetized mouse to enable real-time imaging with sub-micron resolution through the meninges and into the superficial brain parenchyma. In reporter mice in which selected cell types express fluorescent proteins, imaging after infection with fluorescent pathogens (lymphocytic choriomeningitis virus, Trypanosoma brucei or Plasmodium berghei) has shown strong recruitment to the cortical meninges of immune cells, including neutrophils, T cells, and putative dendritic cells and macrophages. Without special labeling, the boundaries between the dura mater, the leptomeninx, and the parenchyma are not directly visualized in intravital two-photon microscopy, but other landmarks and characteristics, which we illustrate, allow the researcher to identify the compartment being imaged. While most infectious meningitides are localized mainly in the dura mater, others involve recruitment of immune cells to the leptomeninx.
- [Efferent innervation of the arteries of human leptomeninx in arterial hypertension]. [Journal Article]
- MMorfologiia 2009; 135(3):35-41
- Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diam…
Structure of the efferent nerve plexuses (adrenergic, acetylcholinestherase- and cholinacetyltranspherase-positive, NO-dependent), was studied in the arteries of human leptomeninx with different diameters. Material was obtained from the corpses of the healthy people and of the patients with initial stages of arterial hypertension (AH). It was shown that the concentrations of cholinergic and adrenergic nerve fibers and varicosities in axon terminal part, innervating the arteries with the diameters ranging from 450 till 100 microm, were not significantly different. In these arteries, NO-ergic plexuses were also detected. In patients with AH, regardless the arterial diameters, the significant increase (up to 15-20%) of adrenergic nerve fiber and varicosity concentrations was found. The changes in cholinergic nerve fiber concentration were found to depend on the vessel diameter: the significant decrease of these parameter was observed only in arteries with the diameter of 100-200 microm. No significant changes in nerve plexus concentration was noticed in the arteries with greater or smaller diameter. In NO-ergic neural conductors, the enzyme activity decreased only in the large arteries, and remained almost unchanged in the small vascular branches. The changes in the vasomotor innervation described in AH, are interpreted as a vasomotor innervation dysfunction of the leptomeninx arteries that may result in the hemodynamic disturbances.
- Autopsy case of Gaucher disease type I in a patient on enzyme replacement therapy. Comments on the dynamics of persistent storage process. [Case Reports]
- JIJ Inherit Metab Dis 2009; 32(4):551-9
- We report a female patient with Gaucher disease (GD) type I on ERT (imiglucerase) for 5 years, which led to a significant general improvement. Aged 59 years she underwent an episode of altitude sickn…
We report a female patient with Gaucher disease (GD) type I on ERT (imiglucerase) for 5 years, which led to a significant general improvement. Aged 59 years she underwent an episode of altitude sickness followed by sepsis, disseminated intravascular coagulation, and multiorgan failure. She succumbed to a cerebral haemorrhage. Autopsy revealed liver cholestatic cirrhosis and multifocal liver carcinoma with immunophenotype compatible with cholangiocarcinoma. Analysis of the storage process revealed its absence or very low levels in the majority of liver and spleen macrophages. Gaucher cells (GCs) were seen only as occasional aggregates of various sizes in these organs. GCs were seen also in the leptomeninx of the cerebellum and as infrequent perivascular clusters in both the grey and white cerebral matters. Bone marrow was heavily infiltrated with GCs, especially in the adipocyte-rich part. GCs in this location displayed varied degrees of cytoplasmic vacuolation unrelated to the lysosomal compartment, caused by droplets of triglyceride, and interpreted as due to resorption of fragments of altered white adipocytes. All these observations point to the relative efficacy of ERT in covering the standard substrate load, which should not be exceeded as it would lead to the evolution of mature GCs. The results are discussed in relation to our recently published hypothesis on GD cell pathology.
- Vinblastine and doxorubicin administration to pregnant mice affects brain development and behaviour in the offspring. [Journal Article]
- NNeurotoxicology 2009; 30(4):647-57
- CONCLUSIONS: The current preclinical data reveal subtle changes in behaviour and transiently also in brain morphology in the mice that were prenatally exposed to vinblastine or doxorubicin.
- Intradural squamous cell carcinoma in the sacrum. [Case Reports]
- WJWorld J Surg Oncol 2009 Feb 11; 7:16
- CONCLUSIONS: We report the first case of a patient with intradural squamous cell carcinoma with unknown origin that developed independently in the sacrum.
- Primary diffuse leptomeningeal gliomatosis in a 2-year-old girl. [Case Reports]
- SNSurg Neurol 2009; 71(6):713-9, discussion 719
- CONCLUSIONS: Primary diffuse leptomeningeal gliomatosis must be included in the differential diagnosis of diffuse leptomeningeal contrast enhancement in young children. There are promising treatment options that need to be carefully evaluated.
- [Intravascular lymphomatosis complicated with marked tumoral thrombosis of the brain venous system including dural sinuses. An autopsy case report with 5 months' follow-up and fatal outcome]. [Case Reports]
- RSRinsho Shinkeigaku 2006; 46(10):707-11
- A 55-year-old man presented with mist, ptosis, and headache. Repeated imaging studies of the brain showed wandering lesions with small hemorrhage and/or infarct-like change. Leptomeningeal enhancemen…
A 55-year-old man presented with mist, ptosis, and headache. Repeated imaging studies of the brain showed wandering lesions with small hemorrhage and/or infarct-like change. Leptomeningeal enhancement was noted. Angiography revealed filling defects in dural sinuses, particularly in the left cavernous sinus. Under the diagnosis of dural sinus thrombosis accompanied with rhinitis, antibiotics and anticlotting drugs were administered. Rhinitis was improved, however, the cavernous sinus lesion remained and grew. Autopsy revealed that large B-cell lymphoma occupied the cavernous sinuses and made a mass involving sella turcica, left sphenoid bone, hypophysis. No tumor mass in the brain or tumor dissemination in the leptomeninx was observed. Intima of the brain venous system, however, was widely involved by lymphoma cells admixed with thrombi, which produced occlusion of the leptomeningeal veins and dural sinuses. Various figures of recanalization were also present. It seems that a unique type of thrombosis, i.e. tumoral thrombosis of leptomeningeal veins and dural sinuses, caused by intravascular lymphoma resulted in fatal outcome with multiple brain lesions like hemorrhagic infarct. Recanalization may partly explain transient resolutions of these multiple lesions. It may be suggested that intravascular lymphomatosis can cause marked phlebothrombosis of the brain and can mimic dural sinus thrombosis.
- Cases of glioblastoma multiforme metastasizing to spinal cord. [Case Reports]
- NINeurol India 2006; 54(4):428-30
- Cases of glioblastoma multiforme (GBM) metastasizing to the leptomeninx or the intramedullary spine are quite rare and prognoses are relatively poor. We present three cases of GBM with spinal metasta…
Cases of glioblastoma multiforme (GBM) metastasizing to the leptomeninx or the intramedullary spine are quite rare and prognoses are relatively poor. We present three cases of GBM with spinal metastasis, one of which also had leptomeningeal dissemination. Three patients with GBM were admitted to our clinic for postoperative radiotherapy after surgery. Leptomeningeal metastasis and dissemination were diagnosed with magnetic resonance imaging. Radiotherapy provided only temporary relief from pain with small improvement in neurological deficit but no survival advantage.
New Search Next
- Histological brain alterations following prenatal methamphetamine exposure in rats. [Journal Article]
- CACongenit Anom (Kyoto) 2006; 46(4):180-7
- When pregnant women abuse methamphetamine, the foremost concern is the potential adverse effect of this substance on fetal development. Clinical studies in humans have found that exposure to methamph…
When pregnant women abuse methamphetamine, the foremost concern is the potential adverse effect of this substance on fetal development. Clinical studies in humans have found that exposure to methamphetamine during brain development can cause neurobehavioral abnormalities, such as aggressive behavior, learning problems, and poor social adaptation. In the present study, we examined the effects of prenatal methamphetamine exposure on brain development in rats. The first group of pregnant rats was administered methamphetamine at a dose of 5 mg/kg/day during gestational day (GD 10 to GD 20 [MA]. The second group of pregnant rats was injected with saline vehicle only [SAL]. On GD 21 their fetuses were removed and fetal brains were observed. We found various types of morphological damage in MA fetal brains, including microgyria, ectopia, and hemorrhage. In some cases, abnormal distribution of the leptomeninx, such as breach or accumulation, was observed in addition to these histological abnormalities. Therefore, we examined the expression of laminin, which is an important component of the pia mater, in the fetal brains. However, Western blot analysis revealed that there was no difference in expression amount of laminin in whole fetal brain between the MA and SAL groups. We concluded that methamphetamine use during pregnancy can cause histological brain alterations in fetuses. Morphological alterations of brain seen in the present study and previous human studies following prenatal exposure to methamphetamine might be related to the neurobehavioral abnormalities seen in patients who had been exposed to methamphetamine in utero.