RESUMEN
We induced percutaneous spinal cord injuries (SCI) using a balloon catheter in 45 rats and transplanted human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) at the injury site. Locomotor function was significantly improved in hUCB-MSCs transplanted groups. Quantitative ELISA of extract from entire injured spinal cord showed increased expression of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neurotrophin-3 (NT-3). Our results show that treatment of SCI with hUCB-MSCs can improve locomotor functions, and suggest that increased levels of BDNF, NGF and NT-3 in the injured spinal cord were the main therapeutic effect.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Trasplante de Células Madre de Sangre del Cordón Umbilical , Regulación de la Expresión Génica , Traumatismos de la Médula Espinal/terapia , Animales , Ensayo de Inmunoadsorción Enzimática , Perfilación de la Expresión Génica , Humanos , Locomoción , Factor de Crecimiento Nervioso/genética , RatasRESUMEN
Here, percutaneous spinal cord injury (SCI) methods using a balloon catheter in adult rats are described. A balloon catheter was inserted into the epidural space through the lumbosacral junction and then inflated between T9-T10 for 10 min under fluoroscopic guidance. Animals were divided into three groups with respect to inflation volume: 20 µL (n = 18), 50 µL (n = 18) and control (Fogarty catheter inserted but not inflated; n = 10). Neurological assessments were then made based on BBB score, magnetic resonance imaging and histopathology. Both inflation volumes produced complete paralysis. Gradual recovery of motor function occurred when 20 µL was used, but not after 50 µL was applied. In the 50 µL group, all gray and white matter was lost from the center of the lesion. In addition, supramaximal damage was noted, which likely prevented spontaneous recovery. This percutaneous spinal cord compression injury model is simple, rapid with high reproducibility and the potential to serve as a useful tool for investigation of pathophysiology and possible protective treatments of SCI in vivo.
Asunto(s)
Embolectomía con Balón/métodos , Compresión de la Médula Espinal/terapia , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
The use of human umbilical cord blood-derived mesenchymal stem cells for cell transplantation therapy holds great promise for repairing spinal cord injury. Here we report the first clinical trial transplantation of human umbilical cord (hUCB)-derived mesenchymal stem cells (MSCs) into the spinal cord of a dog suspected to have fibrocartilaginous embolic myelopathy (FCEM) and that experienced a loss of deep pain sensation. Locomotor functions improved following transplantation in a dog. Based on our findings, we suggest that transplantation of hUCB-derived MSCs will have beneficial therapeutic effects on FCEM patients lacking deep pain sensation.
Asunto(s)
Enfermedades de los Cartílagos/veterinaria , Trasplante de Células Madre de Sangre del Cordón Umbilical , Enfermedades de los Perros/terapia , Embolia/veterinaria , Células Madre Mesenquimatosas/metabolismo , Enfermedades de la Médula Espinal/veterinaria , Animales , Enfermedades de los Cartílagos/etiología , Enfermedades de los Cartílagos/terapia , Trasplante de Células Madre de Sangre del Cordón Umbilical/veterinaria , Enfermedades de los Perros/etiología , Perros , Embolia/etiología , Embolia/terapia , Femenino , Humanos , Células Madre Mesenquimatosas/citología , Enfermedades de la Médula Espinal/etiología , Enfermedades de la Médula Espinal/terapia , Resultado del TratamientoRESUMEN
OBJECTIVE: The aims of this study were to investigate the interference of the brain activation during a passive movement task (PMT) by retained acupuncture at the ST 36 acupoint and to compare these effects between normal brain and Parkinson's disease (PD) brain. METHODS: Functional magnetic resonance imaging (fMRI) techniques have been used to study neurophysiology in animals. Eight healthy beagle dogs were divided into two groups of four dogs each, a normal control group and a PD model group. PD was induced by intravenous injection of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl. During fMRI, the PMT was performed in the right tarsal joint during three different sessions, which consisted of PMT only, PMT while an acupuncture needle was inserted at the ST 36 acupoint, and PMT while needle was inserted at a sham point. RESULTS AND DISCUSSION: Standard veterinary neurological examination was performed on dogs with MPTP-induced PD. A homogeneous grade similar to human PD patients was evident in all dogs. The fMRI study showed that insertion of the acupuncture needle at acupoint ST 36 significantly affected the proprioceptive brain activation by decreasing blood oxygenation level-dependent signal intensity in basal ganglia, limbic system, and cerebellum. Compared with normal and PD brain, we suggest that acupuncture at ST 36 has different modulation effects depending on the pathologic condition of the brain. The study provides evidence of the potential clinical applications of retained acupuncture at ST 36 for rehabilitation therapy of PD patients.
Asunto(s)
Terapia por Acupuntura/métodos , Modelos Animales de Enfermedad , Imagen por Resonancia Magnética/métodos , Trastornos Parkinsonianos/fisiopatología , Trastornos Parkinsonianos/rehabilitación , Animales , Encéfalo/patología , Encéfalo/fisiopatología , Perros , Femenino , Masculino , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Trastornos Parkinsonianos/patologíaRESUMEN
The objective of this study was to differentiate the neuronal responses, which was related or unrelated, to pain associated with acupuncture stimulation, and to localize the brain regions with response to stimulation that is unrelated to pain by using Blood Oxygen Level Dependent (BOLD) functional MRI (fMRI). BOLD fMRI was performed in six normal healthy beagle dogs, during placebo and verum acupuncture stimulations, at the right side of BL60 (KunLun) acupoint before and after local anesthesia of the acupoint. The order of the four sessions was placebo; verum acupuncture stimulation; before local anesthesia; and followed by the same stimulation after local anesthesia. One-sample t-test analysis was performed to localize the activated or deactivated areas, during both pre-anesthesia and post-anesthesia. In order to compare the pre-anesthesia to post-anesthetic responses, and placebo to verum acupuncture stimulation, within-subject analysis was performed. The post-anesthetic verum acupuncture stimulation resulted in increased activations in the left somatic afferent area I and II, right visual and auditory association area, and the descending reticular activating system of the brainstem. In addition, differential areas during post-anesthesia compared to that of the pre-anesthesia were in the left olfactory peduncle and descending reticular activating system of the brainstem. These results indicate that the areas of specific neural pathway are considered to be unrelated to the pain response during acupuncture stimulation.
Asunto(s)
Puntos de Acupuntura , Terapia por Acupuntura , Mapeo Encefálico , Encéfalo/fisiología , Vías Nerviosas/fisiología , Neuralgia/fisiopatología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Mapeo Encefálico/métodos , Perros , Imagen por Resonancia Magnética/métodos , Modelos Animales , Vías Nerviosas/fisiopatología , Oxígeno/sangreRESUMEN
The goal of this study was to prove the possibility of using silicone stents broadly used for human medicine in canine obstructive tracheal disease. A silicone stent anatomically designed for canine trachea was tested on 5 beagle dogs for 8 weeks. The stent was carefully inserted using a newly developed delivery device under fluoroscopic guidance. There were no technical difficulties in placing the stent during the procedure. Previously reported complications of airway stenting such as stent migration or granulation tissue formation did not occur in any of the cases. In addition, removal of the stent was as simple as inserting it, and complications were absent. The stent introduced in this study could possibly be applied to various canine obstructive tracheal diseases.
Asunto(s)
Enfermedades de los Perros/cirugía , Siliconas/uso terapéutico , Stents/veterinaria , Enfermedades de la Tráquea/veterinaria , Animales , Broncoscopía/instrumentación , Broncoscopía/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Perros , Masculino , Proyectos Piloto , Radiografía , Enfermedades de la Tráquea/diagnóstico por imagen , Enfermedades de la Tráquea/cirugíaRESUMEN
BACKGROUND: Many reports have described tracheal replacement using aortic allografts, with varying results and minimal understanding of the mechanism of tracheal regeneration. The present study attempted tracheal regeneration in adult dogs using fresh aortic allografts (FAA) and cryopreserved aortic allografts (CAA). MATERIALS AND METHODS: Twelve adult beagles underwent tracheal resection and were transplanted with FAA (n = 5) or CAA (n = 7). Animals were followed-up with serial radiography and magnetic resonance imaging, and were euthanized at predetermined times up to 16 mo post-surgery. RESULTS: There were no procedural deaths, but two animals died due to stent migration. Stent migration occurred in seven of the 12 animals. Evidence of regeneration of tracheal epithelium was observed in the surviving animals, with the transformation of squamous metaplasia to mucociliary epithelium being time-dependent. Islet of cartilage were observed in animals after 6 mo, but ring-like cartilage structures were absent, even after 16 mo. During autopsy, axial graft contractions up to 68% were observed. Serial radiographs show that most of the contraction occurred within 1 mo. The results of the MRI showed that the graft area was strongly enhanced for up to 2 mo, but was clearly reduced after 3 mo. CONCLUSIONS: Tracheal replacement in adult dogs using FAA or CAA is feasible. However, immaturity of the neotracheal cartilage did not allow the tissue to function as native tracheal tissue. Prolonged stenting should be considered in adult if the procedure is to be clinically contemplated.
Asunto(s)
Aorta/trasplante , Criopreservación , Tráquea/fisiología , Tráquea/cirugía , Trasplantes , Animales , Aorta/patología , Perros , Imagen por Resonancia Magnética , Modelos Animales , Radiografía Torácica , Regeneración/fisiología , Stents , Tráquea/patología , Trasplante Homólogo , Resultado del TratamientoRESUMEN
The aim of this study was to quantitatively investigate the chronic ethanol-induced cerebral metabolic changes in various regions of the rat brain, using the proton high resolution magic angle spinning spectroscopy technique. The rats were divided into two groups (control group: N=11, ethanol-treated group: N=11) and fed with the liquid diets for 10 weeks. In each week, the mean intake volumes of liquid diet were measured. The brain tissues, including cerebellum (Cere), frontal cortex (FC), hippocampus (Hip), occipital cortex (OC) and thalamus (Thal), were harvested immediately after the end of experiments. The ex vivo proton spectra for the five brain regions were acquired with the Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence at 500-MHz NMR spectrometer. All of the spectra were processed using the LCModel software, with simulated basis-set file, and the metabolite levels were referenced to total creatine. In the ethanol liquid diet group, there were significant increases in the metabolites ratio levels, as compared to control (Cere: alanine, glutathione, and N-acetlyaspartate; FC: phosphocholine and taurine; Hip: alanine, glutamine, and N-acetylaspartate; OC: glutamine; Thal: alanine, γ-aminobutyric acid, glutamate, glycerophosphocholine, phosphocholine, taurine, and free choline). However, in the ethanol liquid diet group, the myo-inositol levels of the OC were significantly lower. The present study demonstrates how chronic ethanol consumption affects cerebral metabolites in the chronic ethanol-treated rat. Therefore, this result could be useful to pursue clinical applications for quantitative diagnosis in human alcoholism.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Alcoholismo/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Etanol/toxicidad , Animales , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
It is well known that a variety of stressors induces a significant alteration in various putative neurotransmitters in the mammalian CNS. However, relatively little attention has been paid on the alteration of central glutamate neurotransmission, which is a major excitatory neurotransmitter in the brain. The present study aimed to determine whether acute restraint stress induces the changes in neurotransmitter level, especially glutamate, in rat brain and to examine whether 1-h recovery time after the termination of stress can revert to its pre-stress state. In vivo ¹H-NMR spectra were acquired from the cerebral cortex and hippocampus (control: N = 10, stress: N = 10, stress + 1 h rest: N = 10) immediately or after 1 h rest from restraint stress. All in vivo proton spectra were automatically analyzed using LCModel. We found that acute restraint stress induced significant increase in glutamate concentrations in the cerebral cortex and the hippocampus of rat. However, the level could not revert to its pre-stress state by the end of 1-h recovery period in cerebral cortex of rats. In addition, glutamine/glutamate ratio, which may function as an index of the glutamatergic neurotransmission, was significantly lower in the cerebral cortex of both stress and 1 h stress + 1 h recovery groups, as compared to control. Our finding may provide important evidence for altered glutamatergic activity after the stress and suggest a potential biochemical marker for eventual diagnosis and/or therapy monitoring in mood disorder.
Asunto(s)
Corteza Cerebral/metabolismo , Ácido Glutámico/biosíntesis , Hipocampo/metabolismo , Espectroscopía de Resonancia Magnética , Restricción Física/fisiología , Animales , Ácido Glutámico/metabolismo , Masculino , Protones , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Restricción Física/psicología , Factores de Tiempo , Regulación hacia Arriba/fisiologíaRESUMEN
Subanesthetic doses of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, impair prefrontal cortex (PFC) function in the rat and produce symptoms in humans similar to those observed in patients with schizophrenia. In the present study, in vivo (1) H-MRS and ex vivo (1) H high-resolution magic angle spinning (HR-MAS) spectroscopy was used to examine the brain metabolism of rats treated with subanesthetic doses of ketamine (30 mg/kg) for 6 days. A single voxel localization sequence (PRESS, TR/TE = 4000/20 ms and NEX=512) was used to acquire the spectra in a 30-µl voxel positioned in the cerebral cortex (including mainly PFC) of the rats (ketamine group: n=12; saline group: n=12) anesthetized with isoflurane. After the in vivo (1) H-MRS acquisition, the animals were sacrificed and the cerebral cortex tissues were extracted (ketamine group: n=7; saline group: n=7) for ex vivo (1) H HR-MAS spectroscopy (CPMG sequence, 2.0-s presaturation delay, 2.0-s acquisition time, 128 transients and 4-ms inter-pulse delay) using a 500-MHz NMR spectrometer. All proton metabolites were quantified using the LCModel. For the in vivo spectra, there was a significant increase in glutamate concentration in the cerebral cortex of the ketamine group compared with the controls (p<0.05). For the ex vivo HR-MAS spectra, there was a significant increase in the glutamate/total creatine ratio, and a decrease in the glutamine/total creatine and glutamine/glutamate ratios in the cerebral cortex tissue of the ketamine group compared with the controls. The results of the present study demonstrated that administration of subanesthetic doses of ketamine in the rat may exert at least part of their effect in the cerebral cortex by activation of glutamatergic neurotransmission.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Ácido Glutámico/metabolismo , Ketamina/farmacología , Esquizofrenia/metabolismo , Animales , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of the dopaminergic neurons in the substantia nigra pars compacta, which projects to the striatum. We induced a selective loss of nigrostriatal dopamine neurons, by infusing the mitochondrial complex 1 inhibitor 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) into adult beagle dogs (N=5). Single voxel ¹H water suppressed magnetic resonance spectroscopy (¹H-MRS) at 3 T was used to assess the metabolic changes in the striatum of canine before and after MPTP intoxication. The metabolite spectra obtained from the striatum (voxel size: 2 cm³) showed a lower N-acetyl aspartate to total creatine (creatine+phosphocreatine) ratio after MPTP intoxication. There were no significant differences in other metabolite ratios such as glutamate+glutamine, choline-containing compounds (glycerophosphocholine+phophorylcholine and myo-inositol). Our findings indicated that ¹H-MRS is a sensitive, noninvasive measure of neural toxicity and biochemical alterations of the striatum in a canine model of PD, and further studies are needed to confirm brain metabolic changes in association with progression of MPTP-intoxication.
Asunto(s)
1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Ácido Aspártico/análogos & derivados , Colina/metabolismo , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Creatina/metabolismo , Modelos Animales de Enfermedad , Intoxicación por MPTP/inducido químicamente , Intoxicación por MPTP/metabolismo , Animales , Ácido Aspártico/metabolismo , Perros , Femenino , Humanos , Masculino , Distribución TisularRESUMEN
Human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) have significant therapeutic potential in cell-based therapies following spinal cord injury (SCI). To evaluate this potential, we conducted our preliminary investigations on the remyelination of injured spinal cords with hUCB-MSC transplantations and we observed its long term effects on dogs with SCI. Of the ten injured dogs, seven were transplanted with hUCB-MSCs 1 week after SCI, whereas the remaining three dogs were not transplanted. Two transplanted dogs died over the first month after transplantation because of urinary tract infection, bedsores and sepsis. The SCI dogs showed no improvement in motor and sensory functions and their urinary dysfunction persisted until they were euthanized (from 3 months to 1 year) while hind-limb recovery in 4 dogs among the five transplanted dogs was significantly improved. In the recovered dogs, functional recovery was sustained for three years following transplantation. Histological results from five transplanted dogs showed that many axons were remyelinated by P0-positive myelin sheaths after transplantation. Our results suggest that transplantation of hUCB-derived MSCs may have beneficial therapeutic effects. Furthermore, histological results provided the first in vivo evidence that hUCB-MSCs are able to enhance the remyelination of peripheral-type myelin sheaths following SCI.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Vaina de Mielina/metabolismo , Células de Schwann/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/terapia , Animales , Conducta Animal , Trasplante de Células Madre de Sangre del Cordón Umbilical/psicología , Modelos Animales de Enfermedad , Perros , Humanos , Imagen por Resonancia Magnética/métodos , Recuperación de la Función , Médula Espinal/metabolismo , Médula Espinal/patología , Médula Espinal/cirugía , Traumatismos de la Médula Espinal/patologíaRESUMEN
The forced swimming test (FST) is a useful paradigm that is relatively quick and simple to perform and has been utilized to predict antidepressant activity based on learned helplessness as a model of depression. To date, few studies have used proton magnetic resonance spectroscopy ((1)H-MRS) to assess antidepressant effects in rats. The purpose of this study was to assess desipramine (DMI) effects on the left dorsolateral prefrontal cortex (DLPFC) of the rats, which were randomly assigned to three groups (control, n=10; FST+saline, n=10; FST+DMI, n=10), using single-voxel localization technique. All (1)H-MRS experiments were performed on a Bruker 4.7-T scanner with 400 mm bore magnet, allowing for acquisition of in vivo (1)H point-resolved spectroscopy spectra (TR/TE=3000/30 ms, number of data points=2048, NEX=512, voxel volume=27 µl, scan time=25 min). Proton metabolites were quantified automatically using LCModel software and were expressed as ratios to total creatine (Cr+PCr). Major target metabolites such as N-acetyl aspartate (NAA)+N-acetylaspartylglutamate (NAAG), glutamate+glutamine (Glu+Gln), glycerophosphorylcholine+phosphorylcholine (GPC+PCho), myo-inositol (mIns) and taurine (Tau) were successfully quantified with Cramer-Rao lower boundary ≤10%. There were significantly higher mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios in the FST+saline group compared to the control group. In the FST+DMI group, both mIns/(Cr+PCr) and mIns/(NAA+NAAG) ratios were significantly decreased to the level similar to those in the control group. No other metabolite ratios were significantly different among the three groups. Our findings suggest a possible role of altered mIns level within the left DLPFC of the rat model for depression.
Asunto(s)
Desipramina/administración & dosificación , Inositol/metabolismo , Espectroscopía de Resonancia Magnética/métodos , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Natación/fisiología , Animales , Antidepresivos/administración & dosificación , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Masculino , Tasa de Depuración Metabólica , Protones , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
The forced swim test (FST) is a behavioral paradigm that is predicative of antidepressant activity in rodents. The objective of this study was to examine the effects of desipramine (DMI) pretreatment on behavioral and regional neurochemical responses in the left dorsolateral prefrontal cortex (DLPFC) and hippocampus of mice exposed to the FST using proton magnetic resonance spectroscopy ((1)H-MRS). An ultra short echo stimulated echo acquisition (STEAM) localization sequence (TR/TM/TE=5000/20/2.2ms) was used to measure in vivo proton spectra from the left DLPFC (voxel volume: 7microl) and hippocampus (6microl) of C57BL/6 mice at 9.4T and acquired proton spectra post-processed offline with LCModel. The FST induced significant increase of glutamate (Glu) and myo-inositol (mIns) concentrations in the left DLPFC and hippocampus, respectively. In addition, creatine+phosphocreatine (Cr+PCr) concentrations in the left DLPFC were significantly decreased as compared to control. The metabolic alterations induced by the FST were reverted to level similar to control by acute DMI administration. Our results suggest that glutamatergic activity and glial cell dysfunction may contribute to the pathophysiological mechanisms underlying depression and that modulation of synaptic neurotransmitter concentrations represents a potential target for antidepressant drug development.
Asunto(s)
Conducta Animal/efectos de los fármacos , Química Encefálica/efectos de los fármacos , Desipramina/farmacología , Inhibidores Enzimáticos/farmacología , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Animales , Colina/metabolismo , Creatina/metabolismo , Desipramina/uso terapéutico , Modelos Animales de Enfermedad , Glutamina/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Inositol/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas/métodos , Ratones , Ratones Endogámicos C57BL , Fosfocreatina/metabolismo , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Protones , Estrés Psicológico/tratamiento farmacológico , Natación/psicologíaRESUMEN
This study aimed to find the most sensitive brain region of APP-PS1 mice in early-stage Alzheimer's disease (AD) and to compare the findings with wild-type mouse brain using (1)H high resolution magic angle spectroscopy (HR-MAS). At 18 and 35 weeks of age, the object recognition test was performed with both APP-PS1 and wild-type mice, and the metabolite concentrations were measured in six brain regions at 38-42 weeks using (1)H HR-MAS. Compared to that of wild-type mice, the memory index of the APP-PS1 mice at 18 weeks was not significantly different; however, the memory index of the APP-PS1 mice at 35 weeks was significantly lower. Similar to the results of the (1)H HR-MAS, the [N-acetyl aspartate (NAA)+acetate (Acet)] level in APP-PS1 mice was decreased in the hippocampus and temporal cortex, and the myo-inositol (mIns) level was increased in the entire brain. In addition, scyllo-inositol (sIns) was also elevated in the frontal, occipital, and parietal cortices, hippocampus and thalamus. These findings demonstrated that the behavioral abnormalities of the APP-PS1 mice started at about 30 weeks of age and that the hippocampus and temporal cortex were the most sensitive regions during early-stage AD. In addition, the results of this study confirmed that an increase of mIns and sIns precedes the reduction of the NAA level. These findings demonstrated that the metabolism of the APP-PS1 mouse was associated with early-stage AD. Furthermore, the regional neurochemical profile of APP-PS1 mouse can be used to investigate the pathophysiological mechanisms associated with AD.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Precursor de Proteína beta-Amiloide/genética , Mapeo Encefálico/veterinaria , Encéfalo/metabolismo , Aprendizaje Discriminativo/fisiología , Presenilina-1/genética , Receptores de Superficie Celular/genética , Factores de Edad , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Modelos Animales de Enfermedad , Diagnóstico Precoz , Humanos , Espectroscopía de Resonancia Magnética , Análisis por Apareamiento , Ratones , Ratones Mutantes Neurológicos , Ratones Transgénicos , Presenilina-1/metabolismo , Nexinas de Proteasas , Receptores de Superficie Celular/metabolismo , Reconocimiento en Psicología/fisiología , Análisis Espectral/veterinaria , Marcadores de Spin , Estadísticas no ParamétricasRESUMEN
Although anesthetic agents are known to affect cerebral metabolism, pentobarbital and ketamine have been widely used for animal imaging studies. The purpose of this study is to evaluate alterations in striatum metabolites in dogs between anesthetized with pentobarbital and with ketamine in proton magnetic resonance spectroscopy ((1)H-MRS). (1)H-MRS was performed to ten healthy adult beagle dogs (9-11 kg) at a field strength of 3 T in order to identify metabolic changes after pentobarbital or ketamine administration in the striatum in vivo. Ten dogs were divided into 2 groups as follows: 5 as the pentobarbital-administered group (P group) and 5 as the ketamine-administered group (K group). We found that levels of Glx of the P group was significantly lower than that of the K group (6.90 +/- 0.99 (SD) vs 9.77 +/- 1.14 in 5 dogs, p= 0.003). In addition, the P group also has lower levels of Cr (6.29 +/- 0.44 vs 7.89 +/- 0.91 in 5 dogs, p=0.009) and NAA (5.02 +/- 0.65 vs 6.45 +/- 1.13 in 5 dogs, p=0.041) compared to the K group. However, there were no significant difference between the P group and the K group in striatal levels of Cho and Ins (p>0.1). We demonstrated that MRS-measured metabolites in the specific regions of the brain can be influenced by anesthetic agents.
Asunto(s)
Cuerpo Estriado/fisiología , Ketamina/farmacología , Pentobarbital/farmacología , Analgésicos/farmacología , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Creatinina/metabolismo , Perros , Femenino , Glucosa/metabolismo , Hipnóticos y Sedantes/farmacología , Ketamina/farmacocinética , Espectroscopía de Resonancia Magnética/métodos , Masculino , Pentobarbital/farmacocinética , Fosfocreatina/metabolismo , Taurina/metabolismoRESUMEN
OBJECT: The authors describe a method for percutaneous transplantation of human umbilical cord blood (hUCB)-derived multipotent stem cells (MSCs) under fluoroscopic guidance. The investigators then tested whether percutaneous transplantation of hUCB-derived MSCs improved neurological functional recovery after acute spinal cord injury (SCI). METHODS: The authors induced SCI in 10 dogs by percutaneous balloon compression. The 10 injured dogs were assigned randomly to the following groups (2 dogs each): Group 1, evaluated 2 weeks after sham transplantation; Group 2, evaluated 2 weeks after transplantation; Group 3, evaluated 4 weeks after sham transplantation; Group 4, evaluated 4 weeks after transplantation; and Group 5, evaluated 4 weeks after multispot transplantations. The dogs with sham transplantation (Groups 1 and 3) received the same volume of saline, as a control. A spinal needle was advanced into the spinal canal, and the investigators confirmed that the end of the spinal needle was located in the ventral part of spinal cord parenchyma by using contrast medium under fluoroscopic guidance. The hUCB-derived MSCs were transplanted into the cranial end of the injured segment in 6 injured dogs at 7 days after SCI. RESULTS: Two dogs in Group 2 showed no improvement until 2 weeks after transplantation. Three of 4 dogs (Groups 4 and 5) that received cellular transplants exhibited gradual improvement in hindlimb locomotion from 3 weeks after cell transplantation. The CM-DiI-labeled hUCB-derived MSCs were observed in the spinal cord lesions at 4 weeks posttransplantation and exerted a significant beneficial effect by reducing cyst and injury size. The transplanted cells were positive for NeuN, glial fibrillary acidic protein, and von Willebrand factor. CONCLUSIONS: The percutaneous transplantation technique described here can be easily performed, and it differs from previous techniques by avoiding surgical exposure and allowing cells to be more precisely transplanted into the spinal cord. This technique has many potential applications in the treatment of human SCI by cell transplantation. The results also suggest that transplantation of hUCB-derived MSCs may have therapeutic effects that decrease cavitation for acute SCI.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical/métodos , Células Madre Multipotentes/trasplante , Traumatismos de la Médula Espinal/terapia , Animales , Carbocianinas , Medios de Contraste , Modelos Animales de Enfermedad , Perros , Colorantes Fluorescentes , Fluoroscopía , Humanos , Técnicas para Inmunoenzimas , Distribución Aleatoria , Coloración y Etiquetado/métodosRESUMEN
The present study examined the effects of human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 x 10(6) HUCB-derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate-buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB-derived MSCs expressed neuroprotective factors, such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB-derived MSCs could be useful in clinical treatment of cerebral ischemia.
Asunto(s)
Isquemia Encefálica/patología , Isquemia Encefálica/terapia , Encéfalo/patología , Trasplante de Células Madre Mesenquimatosas , Neuronas/patología , Animales , Astrocitos/metabolismo , Astrocitos/patología , Encéfalo/metabolismo , Isquemia Encefálica/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Diferenciación Celular/fisiología , Trasplante de Células Madre de Sangre del Cordón Umbilical , Perros , Técnica del Anticuerpo Fluorescente , Humanos , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/terapia , Imagen por Resonancia Magnética , Células Madre Mesenquimatosas , Neuronas/metabolismo , Recuperación de la Función , Estadísticas no Paramétricas , Factores de Tiempo , Trasplante Heterólogo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor de von Willebrand/metabolismoRESUMEN
We developed a minimally invasive canine model of spinal cord injury (SCI). A balloon catheter was inserted into the epidural space via the lumbosacral space, and inflated between L2 and L3 for 30 or 60 min under fluoroscopic guidance. Motor function after SCI was assessed using modified Tarlov scale. All seven dogs showed complete paraplegia after the procedure, neurological problems were evident and the modified Tarlov scores remained at zero after the SCI procedure; no improvement in clinical signs was observed. The dogs underwent 3T MR imaging at 3 days and 1 year after SCI. Histopathologic examinations were conducted at 2 weeks, 12 weeks and 1 year after SCI. In the present study, we described an animal model of minimally invasive spinal cord injury using a balloon catheter without laminectomy under fluoroscopic guidance. And, this percutaneous spinal cord compression injury model has many potential applications. The described percutaneous spinal cord compression injury model offers a new means of administering SCI and has many potential applications.
Asunto(s)
Cateterismo/efectos adversos , Modelos Animales de Enfermedad , Compresión de la Médula Espinal/etiología , Compresión de la Médula Espinal/patología , Animales , Conducta Animal , Perros , Espacio Epidural/cirugía , Potenciales Evocados Motores/fisiología , Imagen por Resonancia Magnética/métodos , Factores de TiempoRESUMEN
In acupuncture, the specificity of the point and the reproducibility of the location of the point are prerequisite to the specificity and reproducibility of research involving acupuncture stimulation. The transpositional method, which locates animal acupoints (AAs) on the surface of animal skin corresponding to the anatomic site of a human acupoint, has been generally adopted for research modeling. However, there remains a lack of consensus on the specific location of AA among researchers. The potential problems that the discrepancy in acupoint locating methods causes include the attempt to compare research results. This report is a conceptual study that calls attention to the problems of inconsistency in AA location, and proposes a transpositional 121 AA system in a mouse and rat model. Further discussion, and the establishment of reproducible transpositional AA systems, will prompt further quantitative research and exchange of scientific ideas.