scholarly journals Chronic co-implantation of ultraflexible neural electrodes and a cranial window

2022 ◽  
Vol 9 (03) ◽  
Author(s):  
Rongkang Yin ◽  
Brian C. Noble ◽  
Fei He ◽  
Pavlo Zolotavin ◽  
Haad Rathore ◽  
...  
Keyword(s):  
Cranial Window ◽  
Neural Electrodes

scholarly journals Through the looking glass: A review of cranial window technology for optical access to the brain

2021 ◽  
Vol 354 ◽  
pp. 109100
Author(s):  
Samuel W. Cramer ◽  
Russell E. Carter ◽  
Justin D. Aronson ◽  
Suhasa B. Kodandaramaiah ◽  
Timothy J. Ebner ◽  
...  
Keyword(s):  
Optical Access ◽  
Cranial Window ◽  
Looking Glass ◽  
The Brain

scholarly journals Protocol for constructing an extensive cranial window utilizing a PEO-CYTOP nanosheet for in vivo wide-field imaging of the mouse brain

2021 ◽  
Vol 2 (2) ◽  
pp. 100542
Author(s):  
Taiga Takahashi ◽  
Hong Zhang ◽  
Kohei Otomo ◽  
Yosuke Okamura ◽  
Tomomi Nemoto
Keyword(s):  
Mouse Brain ◽  
Wide Field ◽  
Cranial Window ◽  
Field Imaging ◽  
Wide Field Imaging

scholarly journals An in vivo model allowing continuous observation of human vascular formation in the same animal over time

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yohei Tsukada ◽  
Fumitaka Muramatsu ◽  
Yumiko Hayashi ◽  
Chiaki Inagaki ◽  
Hang Su ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Blood Vessels ◽  
Human Blood ◽  
Molecular Mechanisms ◽  
Human Tumor ◽  
Continuous Observation ◽  
In Vivo Models ◽  
Cranial Window ◽  
Pathological Conditions

AbstractAngiogenesis contributes to numerous pathological conditions. Understanding the molecular mechanisms of angiogenesis will offer new therapeutic opportunities. Several experimental in vivo models that better represent the pathological conditions have been generated for this purpose in mice, but it is difficult to translate results from mouse to human blood vessels. To understand human vascular biology and translate findings into human research, we need human blood vessel models to replicate human vascular physiology. Here, we show that human tumor tissue transplantation into a cranial window enables engraftment of human blood vessels in mice. An in vivo imaging technique using two-photon microscopy allows continuous observation of human blood vessels until at least 49 days after tumor transplantation. These human blood vessels make connections with mouse blood vessels as shown by the finding that lectin injected into the mouse tail vein reaches the human blood vessels. Finally, this model revealed that formation and/or maintenance of human blood vessels depends on VEGFR2 signaling. This approach represents a useful tool to study molecular mechanisms of human blood vessel formation and to test effects of drugs that target human blood vessels in vivo to show proof of concept in a preclinical model.

scholarly journals Attenuation and Recovery of Brain Stem Autoregulation in Spontaneously Hypertensive Rats

1998 ◽  
Vol 18 (3) ◽  
pp. 305-310 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Takanari Kitazono ◽  
Tetsuhiko Nagao ◽  
...  
Keyword(s):  
Brain Stem ◽  
Basilar Artery ◽  
Antihypertensive Treatment ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Large Arteries ◽  
Cranial Window ◽  
Severe Hypotension

Cerebral large arteries dilate actively around the lower limits of CBF autoregulation, mediated at least partly by nitric oxide, and maintain CBF during severe hypotension. We tested the hypothesis that this autoregulatory response of large arteries, as well as the response of arterioles, is altered in spontaneously hypertensive rats (SHR) and that the altered response reverts to normal during long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor. In anesthetized 6- to 7-month-old normotensive Wistar-Kyoto rats (WKY), 4- and 6- to 7-month-old SHR without antihypertensive treatment, and 6- to 7-month-old SHR treated with cilazapril for 10 weeks, local CBF to the brain stem was determined with laser—Doppler flowmetry and diameters of the basilar artery and its branches were measured through a cranial window during stepwise hemorrhagic hypotension. The lower limit of CBF autoregulation shifted upward in untreated SHR to 90 to 105 mm Hg from 30 to 45 mm Hg in WKY, and it reverted to 30 to 45 mm Hg in treated SHR. In response to severe hypotension, the basilar artery dilated by 21 ± 6% (mean ± SD) of the baseline internal diameter in WKY. The vasodilation was impaired in untreated SHR (10 ± 8% in 4-mo-old SHR and 4 ± 5% in 6- to 7-month-old SHR), and was restored to 22 ± 10% by treatment with cilazapril ( P < 0.005). Dilator responses of branch arterioles to hypotension showed similar attenuation and recovery as that of the basilar artery. The data indicate that chronic hypertension impairs the autoregulatory dilation of the basilar artery as well as branch arterioles and that antihypertensive treatment with cilazapril restores the diminished dilation toward normal.

scholarly journals Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Stem ◽  
Topical Application ◽  
Basilar Artery ◽  
Group Versus ◽  
Control Group ◽  
Cranial Window ◽  
Severe Hypotension ◽  
The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

P10.02 Combined methods of a micropump system and a chronic cranial window allows tumor observation with multi photon laser scanning microscopy under continuous treatment

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii28-ii28
Author(s):  
S Weil ◽  
E Jung ◽  
D Domínguez Azorín ◽  
J Higgins ◽  
J Reckless ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Blood Brain Barrier ◽  
Laser Scanning ◽  
Laser Scanning Microscopy ◽  
New Drugs ◽  
Brain Barrier ◽  
Cranial Window ◽  
Blood Brain ◽  
The Brain

Abstract BACKGROUND Glioblastomas are notoriously therapy resistant tumors. As opposed to other tumor entities, no major advances in therapeutic success have been made in the past decades. This has been calling for a deeper biological understanding of the tumor, its growth and resistance patterns. We have been using a xenograft glioma model, where human glioblastoma cells are implanted under chronic cranial windows and studied longitudinally over many weeks and months using multi photon laser scanning microscopy (MPLSM). To test the effect of (new) drugs, a stable and direct delivery system avoiding the blood-brain-barrier has come into our interest. MATERIAL AND METHODS We implanted cranial windows and fluorescently labeled human glioblastoma stem-like cells into NMRI nude mice to follow up on the tumor development in our MPLSM model. After tumor establishment, an Alzet® micropump was implanted to directly deliver agents via a catheter system continuously over 28 days directly under the cranial window onto the brain surface. Using the MPLSM technique, the continuous delivery and infusion of drugs onto the brain and into the tumor was measured over many weeks in detail using MPLSM. RESULTS The establishment of the combined methods allowed reliable concurrent drug delivery over 28 days bypassing the blood-brain-barrier. Individual regions and tumor cells could be measured and followed up before, and after the beginning of the treatment, as well as after the end of the pump activity. Fluorescently labelled drugs were detectable in the MPLSM and its distribution into the brain parenchyma could be quantified. After the end of the micropump activity, further MPLSM measurements offer the possibility to observe long term effects of the applied drug on the tumor. CONCLUSION The combination of tumor observation in the MPSLM and concurrent continuous drug delivery is a feasible and reliable method for the investigation of (novel) anti-tumor agents, especially drugs that are not blood-brain-barrier penetrant. Morphological or even functional changes of individual tumor cells can be measured under and after treatment. These techniques can be used to test new drugs targeting the tumor, its tumor microtubes and tumor cells networks, and measure the effects longitudinally.

Abstract 2579: tPA Contributes To Aggravation of Endothelin and Thromboxane Induced Cerebrovasoconstriction After Hypoxia/Ischemia Through Upregulation of ERK MAPK

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
William Armstead ◽  
Heather Kaczynski ◽  
John Riley ◽  
Douglas Cines ◽  
Abd Al-Roof Higazi
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Tissue Type ◽  
Cranial Window ◽  
Pial Artery ◽  
Erk Mapk ◽  
Cerebral Vasoconstriction ◽  
Type Plasminogen Activator ◽  
Hypoxia Ischemia ◽  
Mitogen Activated Protein ◽  
Global Increase

Introduction: The sole FDA approved treatment for acute stroke is tissue type plasminogen activator (tPA). However, endogenous tPA is upregulated and potentiates impairment of pial artery dilation in response to hypotension after hypoxia/ischemia (H/I) in pigs. Mitogen activated protein kinase (MAPK), a family of at least 3 kinases, ERK, p38 and JNK, is also upregulated after H/I, with ERK contributing to vasodilator impairment. Impairment of stimulus induced vasodilation may result from tonic withdrawal and/or impairment of a vasodilator influence or upregulation of a vasoconstrictor. This study examined the effect of H/I on the vascular response to two important spasmogens released during CNS ischemic disorders, endothelin-1 (ET-1) and thromboxane, and the influence of tPA and ERK MAPK in such responses. Methods: Cerebral ischemia (20 min) was induced via global increase in intracranial pressure via saline infusion into a hollow bolt placed in the cranium (dura intact) while hypoxia (10 min, pO2 35 mm Hg) was produced by decreasing the inspired O2 via inhalation of N2. Vascular responses to topical ET-1 (10-10, 10-8 M) and U 46619 (1, 10 ng/ml) were obtained at 1h post insult. Phosphorylated and total ERK MAPK were measured by ELISA in the CSF of piglets equipped with a closed cranial window. Data (n=5) were analyzed by ANOVA, with significance at p less than 0.05. Results: H/I aggravated pial artery vasconstriction induced by ET-1 and the thromboxane mimic U 46619, which was blocked by EEIIMD, an inhibitor of PAI-1’s vascular activity and signaling of tPA, but not its fibrinolytic action, but unchanged by its inactive analogue EEIIMR. CSF ERK MAPK was increased by H/I and potentiated by tPA. The ERK MAPK antagonist U 0126 blocked H/I induced aggravation of ET-1 and U 46619 vasoconstriction. Discussion: These data indicate that H/I aggravates ET-1 and thromboxane mediated cerebral vasoconstriction through upregulation of tPA and ERK MAPK. These data suggest that thrombolytic therapy for treatment of CNS ischemic disorders can dysregulate cerebrohemodynamics by augmenting vasoconstriction induced by spasmogens co-released during CNS pathology.

Video microscopy of cerebrocortical capillary flow: response to hypotension and intracranial hypertension

1995 ◽  
Vol 268 (6) ◽  
pp. H2202-H2210 ◽  
Author(s):  
A. G. Hudetz ◽  
G. Feher ◽  
C. G. Weigle ◽  
D. E. Knuese ◽  
J. P. Kampine
Keyword(s):  
Cerebral Cortex ◽  
Intracranial Pressure ◽  
Flow Velocity ◽  
Pressure Range ◽  
Perfusion Pressure ◽  
Capillary Flow ◽  
Video Microscopy ◽  
Cell Counting ◽  
Correlation Technique ◽  
Cranial Window

Although autoregulation of cerebral blood flow is well established, the response of cerebral capillary circulation to reduced cerebral perfusion pressure (CPP) is unclear. The objective of this study was to determine whether red cell flow velocity in individual capillaries of the cerebral cortex is maintained during acute decreases in CPP. Microcirculation of the superficial parietal cerebral cortex of adult barbiturate-anesthetized artificially ventilated rats was visualized using a new design of closed-perfused cranial window and epifluorescent-intensified video microscopy. Fluorescein-isothiocyanate-labeled red blood cells (FRBC) injected intravenously were used as markers of capillary flow. CPP, defined as mean arterial pressure minus intracranial pressure, was reduced by controlled hemorrhage or by stepwise elevation of local intracranial pressure. The movement of FRBC in the parenchymal capillary network was video recorded at each pressure level, and FRBC velocity in each capillary was measured off-line with use of the dual-window digital cross-correlation technique. FRBC flux in the capillaries was measured by automated cell counting. FRBC velocity at normal perfusion pressure was 1.47 +/- 0.58 (SD) mm/s and changed little in the perfusion pressure range of 70-120 mmHg. The autoregulatory index in this pressure range was 0.0049 mm.s-1.mmHg-1. Opening of previously unperfused capillaries was not observed. FRBC flux correlated with FRBC velocity, but the latter was maintained in a narrower range than FRBC flux, suggesting a decrease in capillary diameter or hematocrit with decreasing perfusion pressure. The results suggest that flow autoregulation is associated with the maintenance of capillary flow velocity and that capillary recruitment does not contribute to flow autoregulation in the rat cerebral cortex.

Inkjet-Printed Neural Electrodes with Mechanically Gradient Structure

2018 ◽  
Vol 2 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Nana Kokubo ◽  
Masashi Arake ◽  
Kento Yamagishi ◽  
Yuji Morimoto ◽  
Shinji Takeoka ◽  
...  
Keyword(s):  
Gradient Structure ◽  
Neural Electrodes
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