Drugs that lack the ability to cross the blood- brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involve- ment of the glutamatergic system in the aggressiven...Drugs that lack the ability to cross the blood- brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involve- ment of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebel- lomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solu- tion. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.展开更多
Peripheral cisternae and double membranes(PCDMs)in erythroid cells are a landmark of typeⅡcongenital dyserythropoietic anemia(CDA).To gain further insights into the mechanism of dyserythropoiesis,erythroblasts and er...Peripheral cisternae and double membranes(PCDMs)in erythroid cells are a landmark of typeⅡcongenital dyserythropoietic anemia(CDA).To gain further insights into the mechanism of dyserythropoiesis,erythroblasts and erythrocytes in bone marrow were studied in 22 Chinese patients with CDAⅡby transmission electron microscopy.The study demonstrated an increase in all patients in erythroblasts with PCDMs with development from pro-erythroblast to red blood cells.PCDMs often connected with cisternae of endoplasmic reticulum(ER)and the perinuclear space,and were accompanied by karyopyknosis,karyolysis and disruption in polychromatic and orthochromatic erythroblasts.The results suggest that PCDMs are transformed from ER during erythropoiesis and participate in the dissolution and deletion of late erythroid cells in patients with CDAⅡ.展开更多
Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that pla...Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).展开更多
INTRODUCTION The cisterna magna is a space lying between the cerebellum and medulla oblongata that is important in collecting cerebral spinal fluid (CSF) in some patients with contraindication or the impossibility o...INTRODUCTION The cisterna magna is a space lying between the cerebellum and medulla oblongata that is important in collecting cerebral spinal fluid (CSF) in some patients with contraindication or the impossibility of lumbar puncture and in intrathecal administration medication infusion.展开更多
The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent...The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.展开更多
基金supported by Coordenacao de Aperfeicoamento de Pessoal de Nível Superior(CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)-Edital Doencas Neurodegenerativas+1 种基金Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul(FAPERGS)Financiadora de Estados e Projetos(FINEP)
文摘Drugs that lack the ability to cross the blood- brain barrier (BBB) need to be placed directly into the central nervous system. Our laboratory studies the involve- ment of the glutamatergic system in the aggressiveness of glioma, and some ligands of glutamate receptors cannot permeate the BBB. Here, glioma-implanted rats were treated by a technique that delivers ligands directly into the cerebrospinal fluid by puncture into the cisterna cerebel- lomedullaris. Rats were anesthetized and fixed in a rodent stereotactic device. The head was gently tilted downwards at an angle that allowed exposure of the cisterna. Injection into the cisterna was done freehand using a gingival needle coupled to a microsyringe. The efficiency of intracisternal injection was demonstrated using a methylene blue solu- tion. This type of injection is adaptable for any rodent model using small volumes of a variety of other drugs, and is an interesting method for neuroscience studies.
文摘Peripheral cisternae and double membranes(PCDMs)in erythroid cells are a landmark of typeⅡcongenital dyserythropoietic anemia(CDA).To gain further insights into the mechanism of dyserythropoiesis,erythroblasts and erythrocytes in bone marrow were studied in 22 Chinese patients with CDAⅡby transmission electron microscopy.The study demonstrated an increase in all patients in erythroblasts with PCDMs with development from pro-erythroblast to red blood cells.PCDMs often connected with cisternae of endoplasmic reticulum(ER)and the perinuclear space,and were accompanied by karyopyknosis,karyolysis and disruption in polychromatic and orthochromatic erythroblasts.The results suggest that PCDMs are transformed from ER during erythropoiesis and participate in the dissolution and deletion of late erythroid cells in patients with CDAⅡ.
基金supported by AHA Career Development Award 938683 (to PJD)NIH grant R01MH123700 (to MLD)
文摘Since the first electron micrograph of“lace-like structures”over 75 years ago,the endoplasmic reticulum(ER)is now viewed as a highly dynamic,constantly remodeling,continuous network of tubules and cisternae that plays an important role in a broad range of cellular activities from calcium regulation to protein synthesis and trafficking.In neurons,the ER extends from the soma through the axon to presynaptic terminals,and throughout the dendritic arbor into as many as half of all postsynaptic dendritic spines at any given time(Falahati et al.,2022).
文摘INTRODUCTION The cisterna magna is a space lying between the cerebellum and medulla oblongata that is important in collecting cerebral spinal fluid (CSF) in some patients with contraindication or the impossibility of lumbar puncture and in intrathecal administration medication infusion.
基金Japan Society for the Promotion of Science,Grant/Award Number:22K09110。
文摘The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.