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European Review For Medical and... Jun 2020We aimed to compare immunological, histological and oxidative effects of antiepileptic agents; felbamate and levetiracetam on head trauma in rats. (Comparative Study)
Comparative Study
OBJECTIVE
We aimed to compare immunological, histological and oxidative effects of antiepileptic agents; felbamate and levetiracetam on head trauma in rats.
MATERIALS AND METHODS
In this study, 32 Sprague-Dawley genus male rats were used. A closed head trauma mechanism was constituted in order to perform head trauma in rats. Rats were divided into 4 groups, and each group had 8 rats. Following head trauma, Group 1 (Control); normal saline was administered, Group 2; levetiracetam 50 mg/kg was administered, Group 3; felbamate 100 mg/kg was administered, and Group 4; levetiracetam 50 mg/kg and felbamate 100 mg/kg were administered with a combination. Injections were administered intraperitoneally once a day for 20 days. The rats were decapitated at the end of the 20th day. Blood and tissue samples were collected and analyzed for biochemical, immunohistochemical and histological parameters.
RESULTS
Serum cytokine levels in Group 2, 3 and 4 were lower when compared to the control group. In Group 4, in which combined therapy was performed, cytokine levels were found to be the lowest. In Groups 2 and 3, a significant decrease in vascular congestion, mononuclear cell infiltration, hemorrhage, and neural degeneration was noticed in the pia mater. In Group 2, a decrease in vascular congestion and Purkinje cell degeneration was obtained in the cerebellum. However, the best outcomes were determined in Group 4.
CONCLUSIONS
We determined that levetiracetam and felbamate alone are useful with respect to immunological, oxidative and histological alterations. However, their utility is better when used in a combination.
Topics: Animals; Brain Injuries, Traumatic; Cytokines; Dose-Response Relationship, Drug; Felbamate; Injections, Intraperitoneal; Levetiracetam; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley
PubMed: 32633403
DOI: 10.26355/eurrev_202006_21702 -
Journal of Anatomy Oct 2010This review presents an overview of human cortical malformation based on the insights gained from examination of human fetal brains. Examination at early stages of fetal... (Review)
Review
This review presents an overview of human cortical malformation based on the insights gained from examination of human fetal brains. Examination at early stages of fetal brain development allows the identification of the specific pathways which are disrupted in human cortical malformation. Detailed examination of human fetal brains in parallel with studies of genetics and animal models is leading to new concepts of cortical malformations. Here we review a range of human cortical malformations based on a simple classification according to the developmental process thought to be disrupted: neuroblast proliferation, undermigration, overmigration, cortical maturation and destructive lesions. A single case example of a dated intrauterine injury illustrates the spectrum of malformations which may result at a single period in development. The recommended methods of examination of human fetal brain are described together with some of their pitfalls. Detailed neuropathological observations indicate the need for caution in the classification of malformations; radiological findings and pathology of the mature brain do not reflect the specific disruptive pathways of cortical malformations. While many insults may lead to the same pattern of malformation, a single insult can lead to multiple patterns of malformation. Our detailed studies of the human fetal brain suggest that the interface between the meninges and the radial glial end feet may be an intriguing new focus of interest in understanding cortical development.
Topics: Cell Movement; Cell Proliferation; Cerebral Cortex; Humans; Nervous System Malformations; Neurons; Pia Mater
PubMed: 20979584
DOI: 10.1111/j.1469-7580.2010.01288.x -
Acta Ophthalmologica Feb 2020To assess dimensions and associations of the peripapillary border tissue of the choroid (PBT-C) and peripapillary scleral flange (PBT-S).
PURPOSE
To assess dimensions and associations of the peripapillary border tissue of the choroid (PBT-C) and peripapillary scleral flange (PBT-S).
METHODS
The histomorphometric investigation included histological sections of enucleated eyes of Caucasian patients. Using light microscopy, the PBT dimensions were measured.
RESULTS
The study included 85 eyes (85 patients) with an age of 62.0 years (14.1 years) (mean (SD)) (range:37-87 years) and mean axial length of 26.7 mm (3.5 mm) (range:21.0-37.0 mm). Thicker PBT-C thickness (mean: 68.8 μm (35.7 μm)) was associated with shorter axial length (p < 0.001; standardized regression coefficient beta: -0.50), and longer PBT-C length (mean: 531 μm (802 μm)) was correlated with longer axial length (p < 0.001;beta:0.66). PBT-C cross-sectional area (mean 17 050 μm (10 420 μm )) was not significantly associated with axial length (p = 0.37). Decreasing with longer axial length (p < 0.001;beta:0.64), the angle between PBT-C and Bruch's membrane was approximately 90° in non-highly myopic eyes without overhanging Bruch's membrane (BM), it ranged between 100° and 180° in eyes with BM overhanging into the intrapapillary region, and it was close to 0° in eyes with parapapillary gamma zone. Thicker thickness of PBT-S (mean:83 μm (21 μm)) was correlated with presence of glaucoma (p = 0.02). Optic nerve pia mater thickness (mean:109 μm (44 μm)) increased with glaucoma presence (p = 0.046;beta:0.31) but not with axial length (p = 0.34).
CONCLUSIONS
Peripapillary border tissue of the choroid (PBT-C) and PBT-S as continuation of the optic nerve pia mater are distinct structures, with PBT-C remodelling during myopic axial elongation and PBT-S being mostly independent of axial elongation. PBT-C and PBT-S may be of importance for the optic nerve head biomechanics and PBT-C for separation of the choroidal space from the intrapapillary compartment.
Topics: Adult; Aged; Aged, 80 and over; Axial Length, Eye; Bruch Membrane; Choroid; Eye Enucleation; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Myopia, Degenerative; Optic Disk; Sclera
PubMed: 31421014
DOI: 10.1111/aos.14206 -
Cureus Nov 2023Leptomeningeal carcinomatosis (LMC) or leptomeningeal metastasis is defined as metastasis to the pia mater, arachnoid, and subarachnoid space. Only very few patients...
Leptomeningeal carcinomatosis (LMC) or leptomeningeal metastasis is defined as metastasis to the pia mater, arachnoid, and subarachnoid space. Only very few patients with cancer have LMC. In the practice of general surgeons, this diagnosis is rarely, if ever, encountered. We present a rare case of a patient presenting to ED with worsening headaches over several months that developed acute-onset abdominal pain while being evaluated. Further workup showed free air, and the patient was taken emergently to the OR, where a perforated gastric ulcer was identified and biopsied. Pathology revealed gastric adenocarcinoma and subsequent MRI pointed to suspected LMC. Unfortunately, till today there is no effective treatment for advanced-stage gastric cancer, and aggressive intrathecal chemotherapy is only available to mitigate leptomeningeal involvement.
PubMed: 38098918
DOI: 10.7759/cureus.48775 -
Journal of Visualized Experiments : JoVE Jul 2017The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. Using...
The successful development of a subpial adeno-associated virus 9 (AAV9) vector delivery technique in adult rats and pigs has been reported on previously. Using subpially-placed polyethylene catheters (PE-10 or PE-5) for AAV9 delivery, potent transgene expression through the spinal parenchyma (white and gray matter) in subpially-injected spinal segments has been demonstrated. Because of the wide range of transgenic mouse models of neurodegenerative diseases, there is a strong desire for the development of a potent central nervous system (CNS)-targeted vector delivery technique in adult mice. Accordingly, the present study describes the development of a spinal subpial vector delivery device and technique to permit safe and effective spinal AAV9 delivery in adult C57BL/6J mice. In spinally immobilized and anesthetized mice, the pia mater (cervical 1 and lumbar 1-2 spinal segmental level) was incised with a sharp 34 G needle using an XYZ manipulator. A second XYZ manipulator was then used to advance a blunt 36G needle into the lumbar and/or cervical subpial space. The AAV9 vector (3-5 µL; 1.2 x 10 genome copies (gc)) encoding green fluorescent protein (GFP) was then injected subpially. After injections, neurological function (motor and sensory) was assessed periodically, and animals were perfusion-fixed 14 days after AAV9 delivery with 4% paraformaldehyde. Analysis of horizontal or transverse spinal cord sections showed transgene expression throughout the entire spinal cord, in both gray and white matter. In addition, intense retrogradely-mediated GFP expression was seen in the descending motor axons and neurons in the motor cortex, nucleus ruber, and formatio reticularis. No neurological dysfunction was noted in any animals. These data show that the subpial vector delivery technique can successfully be used in adult mice, without causing procedure-related spinal cord injury, and is associated with highly potent transgene expression throughout the spinal neuraxis.
Topics: Animals; Brain; Dependovirus; Female; Genetic Vectors; Green Fluorescent Proteins; Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Spinal Cord; Video Recording
PubMed: 28745630
DOI: 10.3791/55770 -
Evidence-based Complementary and... 2014Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the...
Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [(3)H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole relaxation and p42/44 MAPKs-mediated angiogenesis.
PubMed: 24715930
DOI: 10.1155/2014/408501 -
Scientific Reports Oct 2020Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss. Muse cells are endogenous reparative pluripotent-like stem cells distributed in various tissues. They can selectively home to damaged sites after intravenous injection by sensing sphingosine-1-phosphate produced by damaged cells, then exert pleiotropic effects, including tissue protection and spontaneous differentiation into tissue-constituent cells. In G93A-transgenic ALS mice, intravenous injection of 5.0 × 10 cells revealed successful homing of human-Muse cells to the lumbar spinal cords, mainly at the pia-mater and underneath white matter, and exhibited glia-like morphology and GFAP expression. In contrast, such homing or differentiation were not recognized in human mesenchymal stem cells but were instead distributed mainly in the lung. Relative to the vehicle groups, the Muse group significantly improved scores in the rotarod, hanging-wire and muscle strength of lower limbs, recovered the number of motor neurons, and alleviated denervation and myofiber atrophy in lower limb muscles. These results suggest that Muse cells homed in a lesion site-dependent manner and protected the spinal cord against motor neuron death. Muse cells might also be a promising cell source for the treatment of ALS patients.
Topics: Amyotrophic Lateral Sclerosis; Animals; Disease Models, Animal; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle Strength; Pluripotent Stem Cells; Rotarod Performance Test; Stem Cell Transplantation; Treatment Outcome
PubMed: 33051552
DOI: 10.1038/s41598-020-74216-4 -
American Journal of Physiology. Heart... Feb 2017Water-pipe tobacco smoking is becoming prevalent in all over the world including Western countries. There are limited data on the cardiovascular effects of water-pipe...
Water-pipe tobacco smoking is becoming prevalent in all over the world including Western countries. There are limited data on the cardiovascular effects of water-pipe smoke (WPS), in particular following chronic exposure. Here, we assessed the chronic cardiovascular effects of nose-only WPS exposure in C57BL/6 mice. The duration of the session was 30 minutes/day, 5 days/week for 6 consecutive months. Control mice were exposed to air. WPS significantly increased systolic blood pressure. The relative heart weight and plasma concentrations of troponin-I and B-type natriuretic peptide were increased in mice exposed to WPS. Arterial blood gas analysis showed that WPS caused a significant decrease in [Formula: see text] and an increase in [Formula: see text] WPS significantly shortened the thrombotic occlusion time in pial arterioles and venules and increased the number of circulating platelet. Cardiac lipid peroxidation, measured as thiobarbituric acid-reactive substances, was significantly increased, while superoxide dismutase activity, total nitric oxide activity, and glutathione concentration were reduced by WPS exposure. Likewise, immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome by cardiomyocytes of WPS-exposed mice. Moreover, hearts of WPS-exposed mice showed the presence of focal interstitial fibrosis. WPS exposure significantly increased heart DNA damage assessed by Comet assay. We conclude that chronic nose-only exposure to WPS impairs cardiovascular homeostasis. Our findings provide evidence that long-term exposure to WPS is harmful to the cardiovascular system and supports interventions to control the spread of WPS, particularly amid youths. No data are available on the chronic cardiovascular effects of water-pipe smoke (WPS). Our findings provide experimental evidence that chronic exposure to WPS increased blood pressure, relative heart weight, troponin I, and B-type natriuretic peptide in plasma and induced hypoxemia, hypercapnia, and thrombosis. Moreover, WPS caused cardiac oxidative stress, DNA damage, and fibrosis.
Topics: Animals; Arterioles; Blood Gas Analysis; Blood Pressure; Carbon Dioxide; Carboxyhemoglobin; Comet Assay; Cytochromes c; DNA Damage; Fibrosis; Glutathione; Heart; Immunohistochemistry; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain; Nitric Oxide; Nitric Oxide Synthase Type II; Oxygen; Partial Pressure; Pia Mater; Platelet Count; Smoke; Smoking; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Thrombosis; Time Factors; Nicotiana; Troponin I; Venules
PubMed: 27940964
DOI: 10.1152/ajpheart.00450.2016 -
Acta Histochemica Et Cytochemica Dec 2013Podoplanin is a mucin-type glycoprotein which was first identified in podocytes. Recently, podoplanin has been successively reported as a marker for brain and peripheral...
Podoplanin is a mucin-type glycoprotein which was first identified in podocytes. Recently, podoplanin has been successively reported as a marker for brain and peripheral nerve tumors, however, the distribution of podoplanin-expressing cells in normal nerves has not been fully investigated. This study aims to examine the podoplanin-expressing cell distribution in the mouse head and nervous systems. An immunohistochemical study showed that the podoplanin-positive areas in the mouse peripheral nerve and spinal cord are perineurial fibroblasts, satellite cells in the dorsal root ganglion, glia cells in the ventral and dorsal horns, and schwann cells in the ventral and dorsal roots; in the cranial meninges the dura mater, arachnoid, and pia mater; in the eye the optic nerve, retinal pigment epithelium, chorioidea, sclera, iris, lens epithelium, corneal epithelium, and conjunctival epithelium. In the mouse brain choroid plexus and ependyma were podoplanin-positive, and there were podoplanin-expressing brain parenchymal cells in the nuclei and cortex. The podoplanin-expressing cells were astrocyte marker GFAP-positive and there were no differences in the double positive cell distribution of several portions in the brain parenchyma except for the fornix. The results suggest that podoplanin may play a common role in nervous system support cells and eye constituents.
PubMed: 24610964
DOI: 10.1267/ahc.13035 -
Aging Jun 2021Gamma H2A histone family member X (γH2AX) is a molecular marker of aging and disease. However, radiosensitivity of the different brain cells, including neurons, glial...
Gamma H2A histone family member X (γH2AX) is a molecular marker of aging and disease. However, radiosensitivity of the different brain cells, including neurons, glial cells, cells in cerebrovascular system, epithelial cells in pia mater, ependymal cells lining the ventricles of the brain in immature animals at different postnatal days remains unknown. Whether radiation-induced γH2AX foci in immature brain persist in adult animals still needs to be investigated. Hence, using a mouse model, we showed an extensive postnatal age-dependent induction of γH2AX foci in different brain regions at 1 day after whole body gamma irradiation with 5Gy at postnatal day 3 (P3), P10 and P21. P3 mouse brain epithelial cells in pia mater, glial cells in white matter and cells in cerebrovascular system were more radiosensitive at one day after radiation exposure than those from P10 and P21 mice. Persistent DNA damage foci (PDDF) were consistently demonstrated in the brain at 120 days and 15 months after irradiation at P3, P10 and P21, and these mice had shortened lifespan compared to the age-matched control. Our results suggest that early life irradiation-induced PDDF at later stages of animal life may be related to the brain aging and shortened life expectancy of irradiated animals.
Topics: Animals; Animals, Newborn; Dentate Gyrus; Gamma Rays; Histones; Mice; Survival Analysis; Time Factors
PubMed: 34162763
DOI: 10.18632/aging.203202