Effects of lateral ventricular transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene on cognition in a rat model of Alzheimer's disease

In the present study, transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene into the lateral ventricle of a rat model of Alzheimer＇s disease, resulted in significant attenuation of nerve cell damage in the hippocampal CA1 region. Furthermore, brain-derived neurotrophic factor and tyrosine kinase B mRNA and protein levels were significantly increased, and learning and memory were significantly improved. Results indicate that transplantation of bone marrow-derived mesenchymal stem cells modified with brain-derived neurotrophic factor gene can significantly improve cognitive function in a rat model of Alzheimer＇s disease, possibly by increasing the levels of brain-derived neurotrophic factor and tyrosine kinase B in the hippocampus.

Monoamine alterations and rotational asymmetry in a rat model of Parkinson's disease following lateral ventricle transplantation of human amniotic epithelial cells

BACKGROUND： Human amniotic epithelial cells （HAECs） can differentiate into neurons, astrocytes and oligodendrocytes. They biologically secrete many active neurotrophins and have the capacity to metabolize dopamine enzymes. These features underlie a theoretical basis for the treatment of Parkinson＇s disease （PD）. OBJECTIVE： To investigate the survival and differentiation of transplanted HAECs in the lateral ventricle of PD model rats, and to explore its effect on circling behavior, as well as levels of dopamine （DA）, the metabolite homovanillic acid, dihydroxyphenyl acetic acid, 5-hydroxyindoleacetic acid, and 5-hydroxytryptamine in the striatum. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, and Shanghai Celstar Institute of Biotechnology from May 2007 to December 2008. MATERIALS： HAECs were derived from the placental chorion following caesarean delivery at the Shanghai International Matemal and Child Health Hospital. 6-hydroxydopamine （6-OHDA）, and mouse anti-human Vimentin monoclonal antibody were purchased from Sigma, USA; mouse anti-human nestin and tyrosine hydroxylase （TH） monoclonal antibodies were purchased from Chemicon, USA. METHODS： A total of 114 healthy, adult, Sprague Dawley rats were randomly assigned to two groups： PD model [n = 90, stereotactic microinjection of 2 μL 6-OHDA （3.5 μg/uL） into the striatum] and control （n = 24, no treatment）. The 51 successful PD model rats were randomly divided into 3 subgroups （n = 17）： HAEC, PBS, and model. The HAEC and PBS groups were respectively injected with 10 μL PBS solution containing 1 × 10^5/mL HAECs or 10 pL PBS into the lateral ventricle. The model group was not treated. MAIN OUTCOME MEASURES： TH protein expression in the striatum was evaluated by immunohistochemistry 5 weeks after HAEC transplantation. At 10 weeks, HAEC survival in the lateral ventricle was investigated by immunofluorescent staining; differentiation of HAECs in the lateral and third ventricles was examined by TH immunohistochemistry; concentrations of DA, homovanillic acid, dihydroxyphenyl acetic acid, 5-hydroxyindoleacetic acid, and 5-hydroxytryptamine in the striatum, as well as DA concentration in the cerebrospinal fluid, were measured with high-performance liquid chromatography-electrochemical detection. Circling behavior of PD model rats was consecutively observed for 10 weeks following intraperitoneal injection of amphetamine 1 week after successful model establishment. RESULTS： tn the HAEC group, the number of TH-positive cells significantly increased in the striatum, and circling behavior significantly decreased, compared with the PBS and model groups （P 〈 0.01）. In addition, monoamine concentrations in the striatum, as well as DA concentrations in the cerebrospinal fluid, significantly increased, compared with the PBS group （P 〈 0.05-0.01）. Moreover, a large number of nestin-, vimentin-, and TH-positive cells were observed in the lateral and third ventricles following HAEC injection.CONCLUSION： HAECs survived for 10 weeks with no overgrowth following transplantation into the lateral ventricle of PD model rats. Moreover, the cells differentiated into dopaminergic neurons, which increased DA secretion. HAEC transplantation improved cycling behavior in PD model rats.

Ultrasound guided neural stem cell transplantation through the lateral ventricle for treatment of cerebral palsy in children

A total of 24 children with cerebral palsy were enrolled in this study and underwent ultrasound guided transplantation of neural stem cells through the lateral ventricle. Neural stem cells （3.8 x 106-7.3 x 107） were injected into the lateral ventricles. Mild injury of lateral ventricular blood vessels occurred in only two cases （8.3%）. Seven cases （29.2%） experienced a fever. Clinical manifestations were improved to varying degrees in eight cases （28.0%） within 3 months after transplantation. Patient condition did not worsen, and no patient experienced severe adverse reactions.

Relationship between early nutrition and deep gray matter and lateral ventricular volumes of preterm infants at term-equivalent age

Background The survival of preterm infants has improved over the last decade,but impaired brain development leading to poor neurological outcomes is still a major comorbidity associated with prematurity.The aim of this study was to evaluate the effect of nutrition on neurodevelopment in preterm infants and identify markers for improved outcomes.Methods Totally 67 premature infants with a gestational age of 24–34 weeks and a birth weight of 450–2085 g were included.Clinical parameters and documented diet were collected from medical records.The nutritional analysis comprised the protein,fat,carbohydrate,and energy intake during different time spans.Brain development was assessed by determining deep gray matter(DGM;basal ganglia and thalamus)and lateral ventricular(LV)volumes as measured on cerebral magnetic resonance imaging scans obtained at term-equivalent age(TEA),and potential associations between nutrition and brain volumetrics were detected by regression analysis.Results We observed a negative correlation between mean daily protein intake in the third postnatal week and MRI-measured DGM volume at TEA(P=0.007).In contrast,head circumference at a corrected age of 35 weeks gestation(P<0.001)and mean daily fat intake in the fourth postnatal week(P=0.004)were positively correlated with DGM volume.Moreover,mean daily carbohydrate intake in the first postnatal week(P=0.010)and intraventricular hemorrhage(P=0.003)were revealed as independent predictors of LV volume.Conclusion The study emphasizes the importance of nutrition for brain development following preterm birth.

Intracerebroventricular leptin injection affects neuroendocrine reproductive axis in ovariectomized rats

BACKGROUND：Leptin regulates neuroendocrine function of the hypothalamus-pituitary-ovary axis in humans. OBJECTIVE： To verify effects of intracerebroventricular leptin injection on neuroendocrine function of the hypothalamus-pituitary-ovary axis in ovariectomized rats. DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed at the Basic Medical Institute, Chengde Medical College between June and October 2007. MATERIALS： Thirty healthy, female, Wistar rats were included in this study. The following compounds were used： leptin; gonadotropin-releasing hormone （GnRH） and luteinizing hormone （LH） enzyme-linked immunosorbent assay kits. METHODS： Rats were randomly divided into 3 groups at 1, 2, and 4 hours after injection. Each group was subdivided into control and experimental groups （n = 5 animals per group and time point）. All rats were subjected to bilateral ovariectomy and, beginning on day 7 after surgery, animals received daily subcutaneous injections of estradiol benzoate （2 μg） for 7 consecutive days. The experimental groups were injected with 5 μL leptin （1 g/L） into the lateral cerebral ventricle, and control groups received an equal volume of physiological saline. MAIN OUTCOME MEASURES： GnRH and LH secretion were examined 1, 2, and 4 hours after injection using GnRH and LH ELISA kits, respectively. RESULTS： In the experimental groups, GnRH secretion significantly increased （P 〈 0.01）, followed by LH secretion （P 〈 0.01）, compared with the control groups. GnRH secretion significantly increased 1 hour after leptin injection （P 〈 0.01）. The LH increase was less pronounced, but still significant （P 〈 0.01）; however, the most prominent LH increase occurred between 1 and 2 hours. Both GnRH and LH secretion reached peak levels at 2 hours after leptin injection. Thereafter, both GnRH and LH secretion decreased, but still maintained very high levels, compared with the control group （P 〈 0.01）. CONCLUSION： Intracerebroventricular leptin injection produced similar effects on GnRH and LH secretion in ovariectomized rats, indicating regulatory effects of leptin on GnRH and LH secretion.

Leptin effects on the hypothalamic-pituitary-gonadal axis by activating proopiomelanocortin neurons Correlation between regulatory effects and duration

BACKGROUND：Leptin preserves reproductive functions by stimulating hypothalamic-pituitary-gonadal axis activities at different levels.Some interneurons play an important role in leptin regulation of the gonadal axis.It remains uncertain whether leptin regulates reproductive functions by activating proopiomelanocortin （POMC） neurons.OBJECTIVE：To investigate leptin effects on secretory function of the neuroendocrine-gonadal axis by activating POMC neurons and to observe and verify the relationship between leptin effects and various time points.DESIGN,TIME AND SETTING：The randomized,controlled,animal study was performed at the Basic Institute of Chengde Medical University and the Research Room of Reproductive Immunology of National Research Institute for Family Planning from June to September 2008.MATERIALS：Leptin （Peprotech,USA）,a-melanocyte stimulating hormone and rabbit anti-POMC polyclonal antibody （SC-20148） （Santa Cruz Biotechnology,USA）,follicle stimulating hormone,luteinizing hormone,and gonadotropin releasing hormone enzyme-labeled immunosorbent assay （ELISA） kit （ADL,USA） were used in the present study.METHODS：A total of 60 healthy,female,adult,Wistar rats received 17 （3-estradiol for 5 consecutive days at 15 days after ovariectomy.The rats were randomly assigned to physiological saline （n= 35）,leptin （n = 35）,and a-melanocyte stimulating hormone （n = 20） groups.MAIN OUTCOME MEASURES：Changes in gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone were compared following intraventricular injection of physiological saline,leptin,and a-melanocyte stimulating hormone at various time points.Changes in POMC mRNA and protein expression in the hypothalamus were measured following physiological saline and leptin injection via the lateral ventricle.RESULTS：Compared to the physiological saline group,leptin and a-melanocyte stimulating hormone affected secretion in the hypothalamus-pituitary axis.Leptin affected secretion of gonadotropin releasing hormone,luteinizing hormone,and follicle stimulating hormone,whereas a-melanocyte stimulating hormone inhibited secretion of these hormones.Compared to the physiological saline group,POMC mRNA expression was significantly increased in the hypothalamus at 2 and 4 hours after leptin injection （P〈 0.05）,but expression recovered to physiological saline group levels at 6 hours after injection （P 〉 0.05）.POMC protein expression was significantly increased in the hypothalamus at 4 and 6 hours after leptin injection （P〈 0.05）.CONCLUSION：Leptin affects secretory function of the neuroendocrine-gonadal axis through combined effects on POMC neurons and other pathways.Results suggested that the regulatory effects of POMC neurons were later compared to other neurons.

Intracerebroventricular transplanted bone marrow stem cells survive and migrate into the brain of rats with Parkinson's disease

In this study, 6-hydroxydopamine was stereotaxically injected into the right substantia nigra compact and ventral tegmental area of rats to establish Parkinson＇s disease models. The rats then received a transplantation of bone marrow stromal cells that were previously isolated, cultured and labeled with 5-bromo-2＇-deoxyuridine in vitro. Transplantation of the bone marrow stromal cells significantly decreased apomorphine-induced rotation time and the escape latency in the Morris water maze test as compared with rats with untreated Parkinson＇s disease. Immunohistochemical staining showed that, 5-bromo-2＇-deoxyuridine-immunoreactive cells were present in the lateral ventricular wall and the choroid plexus 1 day after transplantation. These immunoreactive cells migrated to the surrounding areas of the lateral cerebral ventricle along the corpus callosum. The results indicated that bone marrow stromal cells could migrate to tissues surround the cerebral ventricle via the cerebrospinal fluid circulation and fuse with cells in the brain, thus altering the phenotype of cells or forming neuron-like cells or astrocytes capable of expressing neuron-specific proteins. Taken together, the present findings indicate that bone marrow stromal cells transplanted intracerebroventricularly could survive, migrate and significantly improve the rotational behavior and cognitive function of rats with experimentally induced Parkinson＇s disease.

Cerebral corridor creator for resection of trigone ventricular tumors:Two case reports

BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)fibers.New brain retraction systems have been developed to minimize retraction-associated injury.To date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract integrity.This report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR fibers.CASE SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the CCC.Total tumor removal was achieved without additional neurological deficit.DTI showed that the OR fibers were preserved along the surgical field.Preoperative symptoms were alleviated immediately after surgery.Clinical outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale assessments.CONCLUSION In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract integrity.The CCC is thus a promising alternative brain retractor.

Pleomorphic xanthoastrocytoma in the lateral ventricle with extensive subarachnoid dissemination： report of a case and review of the literature

Pleomorphic xanthoastrocytoma （PXA） is a rare benign tumor that is usually located in the superficial cerebral hemisphere.Most reports of PXAs have included only a single case or small series.Therefore,the data with respect to the natural history of this tumor are fragmentary.We report a case of a PXA in the unusual location of the right lateral ventricle with extensive subarachnoid dissemination.To our knowledge,this is a rare case of PXA in the lateral ventricle.In addition,extensive subarachnoid space dissemination of this distinctly benign type of glioma is exceedingly rare.In our case,there was meningeal dissemination and metastases to the bilateral trigeminal nerves and oculomotor nerves.The neuroradiographic features,tumor location,and dissemination were reviewed.

Neuroenteric cyst of the left lateral ventricle: case report and review of the literature

Background:Intracranial supratentorial neuroenteric cysts are very rare lesions in the central nervous system.We described a neuroenteric cyst of the left lateral ventricle in a 38-year old male,which had been confirmed by using immunohistochemistry.To date,this was the first reported case in which the neuroenteric cyst was located in the lateral ventricle.Case presentation:The patient had paroxysmal headache for half a year which exacerbated in the recent two months.MRI showed a 3cm*3cm*2.Scm cyst in the left lateral ventricle.We reported the first case,where the NC in the lateral ventricle was partly resected,provided new evidence to develop the hypothesis on NC etiology.The cyst was left partly due to the strong adherence to the surrounding structures.The final diagnosis was confirmed on histopathological and immunohistochemical analysis of the cyst.Conclusion:Lacking in characterization of the specific imaging features,neuroenteric cyst may be misdiagnosed as other types of cysts preoperatively.At present,surgical excision is the only effective treatment for neuroenteric cysts.Early diagnosis and more treatment options may be available in the future with more cases of neuroenteric cyst being reported and its pathogenesis being understood further,we hope the first reporting of the lateral ventricle NC by now can provide new evidence to NC etiology.

Neuroendoscopy Combined with Lateral Ventricle Drainage and Urokinase Infusion in the Treatment of 20 Patients with Hypertensive Intraventricular Hemorrhage

Objective:To explore the clinical efficacy of neuroendoscopy combined with lateral ventricle drainage and urokinase infusion for the treatment of hypertensive intraventricular hemorrhage.Methods:A retrospective analysis of 20 patients diagnosed with intraventricular hemorrhage between March 2017 and August 2018 at the First Affiliated Hospital of Medical College,Shihezi University(Shiohezi,China)was performed.While actively treating primary lesions,20 patients with intraventricular hemorrhage were selected and treated using minimally invasive neuroendoscopic removal of intraventricular hematoma combined with lateral ventricular drainage and urokinase perfusion according to each patient’s condition.Results:One day after surgery,head computed tomography examination revealed that>50% of the hematoma in the lateral ventricle was removed in 14 cases,and 20%-50% of the hematoma in the other 6 cases.After follow-up,13 patients exhibited satisfactory recovery,5 died(3 due to lung infection,1 due to intracranial infection,and 1 due to multiple organ failure),and 2 were in a vegetative state.Conclusion:Neuroendoscopy should be used as much as possible in treating intraventricular hemorrhage given its advantages of minimal injury,complete removal of hematoma,high safety,and wide clinical applicability.