Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rodent models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed2000

Embryonic donor age and dissection influences striatal graft development and functional integration in a rodent model of Huntington's disease.

The method of embryonic dissection and the age of the donor material remain areas of controversy in the preparation of striatal tissue for intrastriatal implantation. This study explores the relationship between these two parameters with respect to the morphology, function, and physiological integration of the resultant grafts. Tissue derived from embryos of 14 and 16 days of gestation (CRL 10-11 and 14-15 mm, respectively) was prepared as whole, lateral, and medial ganglionic eminence suspensions (WGE, LGE, and MGE, respectively). The embryonic material was implanted into the excitotoxically lesioned striatum of host rats. Grafts derived from E14 LGE attenuated drug-induced rotational bias whereas grafts from E14 MGE ameliorated contralateral deficits in paw reaching. Six months after grafting retrograde tracing of graft projections to the globus pallidus was performed followed by electrical excitation of cortical afferent fibers. Grafts derived from E14 WGE had the largest volume of striatum-like tissue and more striatal neurons compared to LGE from the same donor age. These results suggest that MGE tissue as well as LGE plays a role in the structural and functional integration of striatal grafts.

Acetylcholinesterase↗
PubMed2000

Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb allodynia in a rodent model of chronic central pain after spinal cord hemisection injury.

In the majority of patients, spinal cord injury (SCI) results in abnormal pain syndromes in which non-noxious stimuli become noxious (allodynia). To reduce allodynia, it would be desirable to implant a permanent biological pump such as adrenal medullary chromaffin cells (AM), which secrete catecholamines and opioid peptides, both antinociceptive substances, near the spinal cord. We tested this approach using a recently developed a mammalian SCI model of chronic central pain, which results in development of mechanical and thermal allodynia. Thirty day-old male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4 weeks for recovery of locomotor function and development of allodynia. Nonimmunosuppressed injured animals received either control-striated muscle (n = 7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks posttransplant as measured by paw withdrawals to von Frey filaments, radiant heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated statistically significant reductions in both fore- and hindlimb mechanical and thermal allodynia, but not analgesia, when compared to hemisected animals receiving striated muscle transplants (P < 0.05). Tyrosine hydroxylase immunoreactivity indicated prolonged transplant survival and production of catecholamines. HPLC analysis of cerebrospinal fluid samples from animals receiving AM transplants demonstrated statistically significant increases in levels of dopamine (sevenfold), norepinephrine (twofold), and epinephrine (threefold), compared to control values several weeks following transplant (P < 0.05). By 28 days posttransplant, however, antinociceptive effects were diminished. These results support the therapeutic potential of transplanted AM in reducing chronic central pain following spinal cord injury.

Adrenal Medulla↗
PubMed2001

Effective reduction of neuronal death by inhibiting gap junctional intercellular communication in a rodent model of global transient cerebral ischemia.

Gap junctions assemble astrocytes into syncytia, allowing exchange of metabolites, catabolites, and second-messenger molecules. Connexin43 is the predominant connexin of astrocytic gap junctions. The distribution of gap junction protein connexin43 was analyzed in different subfields of the hippocampal formation as a function of time after transient forebrain ischemia. One decisive key step in understanding why an ischemic insult gradually expands may be to establish how gap junction channels permit dying cells in the ischemic focus to communicate, in particular, with viable cells. The role of gap junctional intercellular communication in the hippocampus under ischemic conditions could be decisive for cell death propagation. We found that the vulnerable CA1/CA2 subfields have a higher density of gap junctions than the resistant CA3/CA4 areas, that changes in the distribution of connexin43 immunoreactivity may correlate with the phenomenon of selective vulnerability, and that inhibition of astrocytic gap junction permeability by octanol restricts the flow of undesirable neurotoxins that could potentially exacerbate neuronal damage. This provides a novel perspective for analysis of the pathophysiology of cerebral ischemia.

Animals↗
PubMed2002

Radiation and regeneration: behavioral improvement and GDNF expression after Gamma Knife radiosurgery in the 6-OHDA rodent model of hemi-parkinsonism.

BACKGROUND: Recent research has demonstrated that the adult mammalian CNS is capable of regeneration. This regeneration is often initiated as a response to thermal, chemical or mechanical injury. The effects of radiation on the mammalian CNS have also been found to aid in certain regeneration processes. METHOD: In our project we examined the potential therapeutic value of radiation induced regeneration of diseased mammalian rat CNS. Eleven Sprague-Dawley rats with 6-hydroxy-dopamine (6-OHDA) induced hemi-parkinsonism were treated in the Leksell Gamma Knife using a single 4 mm collimator shot targeted to the ipsilateral (parkinsonian) caudate-putamen complex. A maximum dose of 140 Gy was used to create a necrotic lesion. Animals were tested behaviorally using the apomorphine-induced rotational behavior model before and up to 6 months after radiosurgery. Histochemical analysis was performed 2 weeks, 1 month and 4 months after radiosurgery. Histological sections were obtained and immunohistochemistry was performed for glial cell line derived neurotrophic factor (GDNF). FINDINGS: The rotational behavior for 11/11 animals (100%) was found to initially worsen at 2 weeks and 4 weeks after radiosurgery before a statistically highly significant reduction in apomorphine induced rotations was observed at 2, 3, and 4 months after radiosurgery (83% reduction by month four; p < 0.0001). For 2/11 animals the rotational behavior almost disappeared indicating near-abolition of parkinsonian behavior. On histological examination, the lesions were easily identified as areas of necrosis about 4 mm in diameter. The region immediately adjacent to the lesion was found to have highly positive expression of GDNF indicating high activity in dopamine-regenerating processes. INTERPRETATION: In this preliminary study we demonstrated that radiosurgical lesioning with the Gamma Knife into the striatum of hemi-parkinsonian animals resulted in significant behavioral improvement of signs of parkinsonism. Since GDNF expression is tightly linked to the dopaminergic system, we conclude that focused radiation is potentially capable of inducing regeneration of dopaminergic pathways in the adult CNS. Further studies with dose deescalation and molecular biological characterization of the regeneration cascades are necessary to gain access to potential clinical value of our observations.

Animals↗
PubMed1998

CSF dynamics in a rodent model of closed head injury.

Using ICP measurements and the bolus injection technique dynamic parameters of the cerebrospinal fluid system as there are pressure-volume-index (PVI) and resistance to CSF outflow (Rout) were investigated in a new model of diffuse closed head injury (CHI) in the rat. It was found that in the absence of brain oedema and ICP alterations an increase in PVI and Rout was present in the early (4h) period following head injury. This may be indicative for a reduction in cerebral blood flow and cerebral blood volume, both shown previously to occur after CHI. Furthermore an early impairment of CSF absorption mechanisms is evident. To answer the question, whether bolus injection techniques are advisable for clinical routine and whether results might have a predictive value, further investigations covering longer observation intervals and in the presence of secondary insults to the brain are necessary.

Animals↗
PubMed1993

The brainstem esophagomotor network pattern generator: a rodent model.

The evidence reviewed in this essay supports the following working model of the central function generator for esophageal peristalsis in the rat: solitarial subnucleus centralis (NTSc) neurons operate in a dual capacity as esophagomotor reflex interneurons and as command neurons programming respective outputs from nucleus ambiguus compact formation (AMBc) motoneurons during secondary and primary peristalsis. In both conditions, there is a critical requirement for cholinergic input which enables NTSc neurons to generate the timed sequence of AMBc motoneuronal activity. In primary peristalsis, the cholinergic coupling mechanism is activated centrally, probably via projections from deglutitive premotor neurons to the parvicellular reticular formation and thence to the NTS. In reflex (or secondary) peristalsis, the cholinergic input could in part be generated by cholinergic vagal viscerosensory fibers innervating the esophagus. Postulated connections between NTS deglutitive neurons and the parvicellular cholinergic neurons of the intermediate reticular formation have yet to be demonstrated. Premotor input from NTSc to AMBc is generated by somatostatinergic and excitatory aminoacidergic neurons. Coactivation of both inputs by cholinergic afferents is necessary to generate esophagomotor output from AMBc neurons. The model under study is derived from investigations into central mechanisms governing striated muscle peristaltic activity. Whether the basic operational principles revealed thus far apply to peristaltic pattern generation in species with a smooth muscle esophagus, requires further investigation.

Animals↗
PubMed1990

A rodent model of infusion brain edema: methodology and pathophysiological effects of saline and protein infusions.

To evaluate the potency of putative secondary mediators of brain edema and their possible contribution to edema related brain dysfunction an infusion model of brain edema was developed in rats. 100 ul of fluid (saline, 20% nonautologous protein) was infused over one hour into the left forebrain white matter through a stereotaxically placed (+1.2 mm ant to bregma, 3 mm lateral and 2.9 mm depth) 25 G needle. Brain tissue hydraulic resistance (Rt), regional cerebral blood flow (rCBF), cortical somatosensory evoked potentials (SEPs) and intracranial pressure (ICP) (intraventricular needle) were monitored during the infusion and rCBF CO2 reactivity (hydrogen clearance), local brain water content (microgravimetry), BBB integrity (Evans Blue 2%) and brain histology (H & E. Solochrome-cyanin) were evaluated after the infusion. Saline infusates caused no physiological dysfunction despite ipsilateral expansion and vacuolation of the subcortical white matter, separation of axonal bundles and a significant decrease (p = 3.8 x 10(-5] in local subcortical tissue specific gravity. Cortical histology and specific gravity adjacent to the infusion locus were normal. Rt significantly decreased (p = 6.5 x 10(-4] during the infusion but there were only minor increases in ICP. Findings with 20% protein infusates were similar despite a focal 65% decrement in the rCBF CO2 reactivity adjacent to the infusion site. This study has shown that a simple and inexpensive model of infusion brain edema can be created in the rat and that it provides a useful model for assessing the physiological effects of mediator compounds in the infusate. Potential applications and methodological improvements for this model are discussed.

Animals↗
PubMed1995

Post-capillary venules in the "milky spots" of the greater omentum are the major site of plasma protein and leukocyte extravasation in rodent models of peritonitis.

Intraperitoneal injection of inflammatory agents in the mouse and rat causes plasma protein and leukocyte extravasation into the peritoneal cavity. Following an intraperitoneal injection of zymosan A, the milky spots of the omentum were the only abdominal sites detected where intravenously administered Monastral Blue labeled interendothelial cell gaps responsible for plasma extravasation. In addition, when colored microspheres were intraventricularly administered to quantify blood flow, the omentum was the only abdominal organ which showed an increase in blood flow during zymosan A peritonitis. A combination of light and electron microscopy, plus measurement of myeloperoxidase activity (a marker of neutrophil accumulation) demonstrated that the omental milky spots are the major route through which leukocytes migrate into the peritoneal cavity. Identical structures in the pleura likewise are the sites of protein leakage into the pleural cavity. In contrast, selective sites of protein and cellular extravasation could not be detected in the synovial lining of the inflamed knee joint.

Animals↗
PubMed1990

An assessment of the risk of neoplasia in long-term ileal reservoirs using the DMH rodent model.

This study was undertaken to determine if the construction of an ileal reservoir induces mucosal changes that can potentiate the effect of a chemical carcinogen (1,2-dimethylhydrazine) on ileal mucosa. Animals were divided into three groups: 1) sham operation (n = 19), 2) total colectomy with ileorectal anastomosis (n = 20), 3) total colectomy with an ileal reservoir made of terminal ileum sutured to the rectum (n = 20). An adaptation period of 12 weeks was allowed to promote fecal stasis and the histologic changes before exposure to weekly subcutaneous injections of DMH (25 mg/kg) for 16 weeks. Sodium butyrate was added to the diet as a tumor promotor. All animals were sacrificed one month later. Fecal stasis, along with enlargement, occurred in all the reservoirs (mean dimensions, 74 X 58 X 43 mm). Their mean volume was 88 +/- 14 ml. The histologic changes in the ileal reservoirs were: chronic inflammation (14/20), villous atrophy (14/20), and atrophy of the glands (8/20). In group 3, five carcinomas were seen. There were three in the duodenum and two in the reservoirs. In contrast, 21 carcinomas were detected in the control groups. There were 17 in the colon, 3 in the jejunum, and 1 in the ileum. No significant difference in the number of carcinomas was seen in the ileum with and without reservoir. Although it is possible to induce carcinomas in ileal reservoirs, the incidence remained significantly less than in the colon. In conclusion, the histologic changes induced by the construction of an ileal reservoir do not increase the risk of malignant transformation in the DMH model for intestinal carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1996

Anxiolytic properties of endogenously occurring pregnanediols in two rodent models of anxiety.

Certain endogenously occurring 3 alpha-hydroxylated, 5-reduced pregnane steroids act at a specific site on the GABAA receptor complex (GRC) to modulate the effects of GABA at its receptor. Modulators that potentiate GABA at the GABAA receptor often possess anxiolytic properties. The anxiolytic potential of four 5-reduced, 3 alpha, 20-pregnanediols, differing only in the stereochemical orientation of the steroid A-ring and the 20-hydroxyl group, were tested in the Vogel test following intracerebroventricular (ICV) administration. The effects of these pregnanediols were compared to those of their 20-ketone analogues, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha, 5 alpha-P) and 3 alpha-hydroxy-5 beta-pregnan-20-one (3 alpha, 5 beta-P). All four pregnanediols tested significantly enhanced punished drinking at doses ranging from 10 to 60 micrograms. The rank order of potency based on the minimum effective dose (MED) observed was 5 alpha-pregnan-3 alpha,20 alpha-diol = 5 beta-pregnan-3 alpha,20 alpha-diol > 5 beta-pregnan-3 alpha,20 beta-diol > 5 alpha-pregnan-3 alpha, 20 beta-diol. 3 alpha,5 beta-P and 3 alpha,5 alpha-P enhanced punished responding when administered at 2.5 and 5 micrograms, respectively. 3 beta,5 alpha-P which is inactive at the GRC was also inactive (up to 100 micrograms) in the Vogel test. The benzodiazepine control diazepam was efficacious when administered at 2.5 micrograms. 5 alpha-Pregnan-3 alpha,20 alpha-diol was further tested in the mouse elevated plus-maze model following systemic administration where it was found to be active in a dose range of 10-40 mg/kg IP. These results raise the possibility that in addition to 3 alpha,5 alpha-P and 3 alpha,5 beta-P, some of their endogenously occurring pregnanediol metabolites may also influence physiological processes related to anxiety via the GRC.

Animals↗