Establishment of a rat model of Cryptococcus neoformans meningitis / 中国感染与化疗杂志

Objective To establish a rat model of Cryptococcus neoformans meningitis. Methods Sprague-Dawley rats were divided into four groups (group A to D). The load of Cryptococcus neoformans was inoculated by intracisternal injection to the animals in Group A (1×105 cfu), Group B (1×106 cfu), Group C (1×107 cfu), and 0.9％ NaCl solution to Group D. The rats were observed after inoculation for their clinical symptoms. On day 14 and day 21 after inoculation, cerebrospinal fluid was sampled and cultured for counting of bacterial colonies. The 28-day mortality of the animals was calculated. Results All the animals in group A (1×105 cfu) survived without any apparent clinical symptoms, and associated with decreasing bacteria load. The animals in group B (1×106 cfu) had mild symptoms associated with low mortality rate and slightly increased bacterial load. The animals in group C (1×107 cfu) showed a lot of symptoms and associated with high mortality rate and significantly increased bacteria load. All the animals in group D (0.9％ NaCl solution) survived with normal activity. No bacterial colony was cultured from the cerebrospinal fluid. Conclusions Intracisternal injection of 1×107 cfu Cryptococcus neoformans to rats could cause apparent clinical symptoms of meningitis. The 28-day mortality rate of such a rat model of Cryptococcus neoformans meningitis is greater than 80％. An ideal rat model of Cryptococcus neoformans meningitis is established successfully.

Rat Cerebrospinal Fluid Treatment Method through Cisterna Cerebellomedullaris Injection / 神经科学通报·英文版

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 involvement 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 cerebellomedullaris. 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 solution. 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.

Intracisternal Cranial Root Accessory Nerve Schwannoma Associated with Recurrent Laryngeal Neuropathy

Intracisternal accessory nerve schwannomas are very rare; only 18 cases have been reported in the literature. In the majority of cases, the tumor origin was the spinal root of the accessory nerve and the tumors usually presented with symptoms and signs of intracranial hypertension, cerebellar ataxia, and myelopathy. Here, we report a unique case of an intracisternal schwannoma arising from the cranial root of the accessory nerve in a 58-year-old woman. The patient presented with the atypical symptom of hoarseness associated with recurrent laryngeal neuropathy which is noted by needle electromyography, and mild hypesthesia on the left side of her body. The tumor was completely removed with sacrifice of the originating nerve rootlet, but no additional neurological deficits. In this report, we describe the anatomical basis for the patient's unusual clinical symptoms and discuss the feasibility and safety of sacrificing the cranial rootlet of the accessory nerve in an effort to achieve total tumor resection. To our knowledge, this is the first case of schwannoma originating from the cranial root of the accessory nerve that has been associated with the symptoms of recurrent laryngeal neuropathy.

Pharmacology of Intracisternal or Intrathecal Glycine, Muscimol, and Baclofen in Strychnine-induced Thermal Hyperalgesia of Mice

Glycine and gamma-aminobutyric acid (GABA) are localized and released by the same interneurons in the spinal cord. Although the effects of glycine and GABA on analgesia are well known, little is known about the effect of GABA in strychnine-induced hyperalgesia. To investigate the effect of GABA and the role of the glycine receptor in thermal hyperalgesia, we designed an experiment involving the injection of muscimol (a GABAA receptor agonist), baclofen (a GABAB receptor agonist) or glycine with strychnine (strychnine sensitive glycine receptor antagonist). Glycine, muscimol, or baclofen with strychnine was injected into the cisterna magna or lumbar subarachnoidal spaces of mice. The effects of treatment on strychnine-induced heat hyperalgesia were observed using the pain threshold index via the hot plate test. The dosages of experimental drugs and strychnine we chose had no effects on motor behavior in conscious mice. Intracisternal or intrathecal administration of strychnine produced thermal hyperalgesia in mice. Glycine antagonize the effects of strychnine, whereas, muscimol or baclofen does not. Our results indicate that glycine has anti-thermal hyperalgesic properties in vivo; and GABA receptor agonists may lack the binding abilities of glycine receptor antagonists with their sites in the central nervous system.

The Effect of Systemic Nicardipine and Intracisternal Nicardipine on the Experimental Cerebral Vasospasm

This study reports the protective of systemic nicardipine and intracisternal nicardipine administration in the three-hemorrhage canine model of chronic cerebral vasospasm. Twenty-one dogs were assigned to one of three groups : control, intravenous nicardipine, and intracisternal nicardipine. All animals received a total of 12ml of fresh unheparinized autologous blood via three cisternal injection. Selective vertebral angiograms were obtained before intravenous nicardipine for 7 days continuously, the other seven were treated by intracisternal nicardipine for 7 days, and the remaining were not treated. Animals were sacrificed at day 9. Comparisons were based on the percentage of reduction in basilar artery diameter(% RBAD). The ultrastructural changes were studied by transmission electron microscopy(TEM). There was a mean reduction(+/- standard deviation) of 54+/-6% in control dogs, 35+/-4% in dogs with intravenous nicardipine, 32+/-6% in dogs with intracisternal dicardipine(difference significant, t-test, P<0.05). The preventive effects of intracisternal nicardipine was superior to those of intravenous nicardipine. There was a strong trend toward reduction of medial necrosis in the basilar artery in dogs with intravenous and intracisternal group compared to control dogs. All basilar arteries showed structural changes with celectron microscopic examination ; these included medial necrosis, lysosome, initial changes, endothelial cell vacuoles, and adventitial erythrocytes, leukocytes. Intimal proliferation was unusual in all three groups, but reduction of intimal proliferation was found in dogs with treatment, and it was believed that vasospasm in this stage is due to long-standing smooth muscle contraction and not to arterial wall thickening. There was significant reduction of blood clot in intracisternal nicardipine group, which may be due to inhibitory action on platelet aggregation of nicardipine. These investigations support the hypothesis that the presence of clotted blood around the intracranial arteries is the cause of vasospasm.

Effect of Calcium Antagonist(Nicardipine) on CBF, CMRO2, and CMRG in Experimental Cerebral Vasopasm

The author investigated the cerebral circulatory and metabolic effects of systemic and intracisternal administration of nicardipine in a canine model of chronic cerebral vasospasm. Twenty-one dogs were assigned to one of three groups; control, intravenous nicardipine, and intracisternal nicardipine. All animals received a total of 12 ml of fresh unheparinized autologous blood via three cisternal injections. Sequential measurements of cerebral blood flow(CBF), cerebral metabolic rate of oxygen(CMRO2), and cerebral metabolic rate of glucose(CMRG) were chacked four times in nine days. Animals were sacrificed at Day 9 and amount of clot remained in brainstem and basal cistern was graded accordingly. Significant improvement of cerebral blood flow was noted in Day 6, Day 9 of intracisternal group and in Day 3, Day 6 of intravenous group(each, p<0.05) with slight better results seen in intracisthernal group. Results of sequential changes of CMRO2 and CMRG indicated possible role of nicardipine in protective effects on deleterious neuronal damage following ischemic changes after vasospasm, but definitive statements on this subject matter should be reserved until further study, espedially on morphologic examinations is carried on, Significantly less amount of clot remained in intracisthernal group may be due to effects of nicardipine in its inhibitory action on platelet aggregation, and/or stimulatory effect on prostacyclin production. These factors along with other possible factors should be speculated.