| Objective To establish the adult canine model of obstructive hydrocephalus by injecting Cyanoacrylic glue into the fourth ventricle and explore: 1. the characteristics of the animal model of hydrocephalus;2. the effects of ventriculoperitoneal shunt and shunt-occlusion on brain compliance in hydrocephalus;3. the pathological changes and variety of the number of dopaminergic neuron of periventricle tissue caused by experimental hydrocephalus.Methods Eighteen adult healthy mongrel dogs, twelve in laboratory group and six in control group, were used for the experiment. All dogs underwent baseline magnetic resonance imaging (MRI) and neurological evaluation prior to hydrocephalus induction, and those dogs with ventricular enlargement before experiment were excluded from the study. Evan's ratios (ventricular width-brain width) were calculated from MRI of single coronal brain slices at the foramen of Monro. After the anaesthesia in vein and intubatton of branches, the right parietal craniectomies were drilled, and ventricular access catheter were inserted. The basic intracranial pressure (ICP) before hydrocephalus induction were measured and recorded. A reservoir was connected the ventricular catheter, and located subcutaneous in order to timely measure ICP after hydrocephalus induction. A midline suboccipital craniectomy was performed and the dura mater was openedalong the midline. The cerebellomedullary cistern and the Fourth ventricle was exposed, then Cyanoacrylic glue was injected into the fourth ventricle of the laboratory group and the same amount of normal saline solution was injected in the fourth ventricle of control group through a silicone tube. All dogs were monitored for 1-8 weeks post-induction using intracranial pressure measurement, neurological fitness assessments and MRI.Eight weeks following surgery, a second MRI examination was performed. On the day after this examination, the animals received measurements of ICP and brain compliance. Compliance was the amount of saline needed to increase ICP from 5 to 15 mmHg and from 15 to 25 mmHg. After the measurements had been obtained, a VP shunt system without a valve was implanted in each animal. We made a primary experiment using an improved shunt with a bracket of the synthetic blood vessel in the shunt operation, and compared the shunt without improvement. All dogs were monitored for 4 weeks post-shunt using neurological fitness assessments and ICP measurement.Four weeks following shunt surgery, measurements of ICP and brain compliance were repeated, following which the shunt systems were obstructed. One week after shunt occlusion, the last measurements were obtained. At the termination of the experiments animals were deeply sedated and brains were extracted and post-fixed for 3-5 days in 4% formaldehyde after one week. The tissues of the brain, such as ependyma, white matter of periventricle, corpus callosum, hippocampus, and cortical movement zone were sliced and stained with hematoxylin and eosin (HE), we use immuohistochemical method and use antibody link with tyrodine hydroxylase which is peculiarly in dopaminergic neuron and display dopaminergic neurons of basic ganglion through show the colour, we can ensure the changes of the mount of dopaminergic neurons in basic ganglion of hydrocephalus canines,so we can assure the pertinency of the symptoms and the mount of dopaminergic neurons in basic ganglion. The results contain three parts.The first part: the establishment and characterization of themodel of obstructive hydrocephalusResults: (D In the laboratory group, one dog was died of acute hydrocephalus, while the other ten were successfully, and one was failed, which meaned that the success inducing rate is 83%. Among the 10 dogs who developed hydrocephalus, three had severe ventricular enlargement, (meaning the change percent in Evan's ratio was 123 ±41%), and another three dogs underwent moderate ventricle enlargement (73 ±15%). Four had mild ventricular enlargement (31±14%). In the control group, one died of anaesthesia, there were no differences after operation for the five dogs (Evan's ratio was 123 ±41%).? The abnormal behavior, such as inappetence, vomit, asthenia, lethargy, persistent gait and balance abnormity, rigor and hypokinesia in the development of the hydrocephalus was observed and recorded. ? Compared with the control group, a significant increase in ICP was observed. Among the dogs in the untreated hydrocephalus stage, ICP remained within the mild elevation (9.98 ±1.84 mm Hg), which was significantly higher than that of the control group (3.82+1.19mm Hg), p <0.05. ? Histological outcomes of the pons adjacent to the glue revealed evidences for a minimal tissue reaction to the glue itself, and it was confirmed no infarction of supratentorial tissues was found.Conclusion (pCanines can be used to establish the models of hydrocephalus by injecting Cyanoacrylic glue into the fourth ventricle. ?We believe that the model resembles LIAS, which is typically insidious, characterized by a long period of onset, and usually associated with mild symptoms. (3) The model established in our study had the following features: 1) uniform obstruction at the fourth ventricle without inflammatory reaction;2) high success rate in induction of hydrocephalus, consistent ventriculomegaly;3) mild increased ICP and clinical symptoms also were mild;4) no infarction confirmed histologically. This model should facilitate the study of the pathophysiology, diagnosis and treatment of chronic hydrocephalus.The second part: the effects of ventriculoperitoneal shunt andshunt-occlusion on brain compliance in hydrocephalusResults: ? After shunt placement, ICP decreased significantly (from 9.98 ± 1.84 mm Hg to4.28±L25mmHg p<0.01) and symptoms of hydrocephalus canine were disappeared in one day. ICP increased again (10.57 ±1.93mmHg, p<0.01, compared with the shunted stage) after shunt occlusion. No significant in ICP was observed between the untreated and shunt-removed stages. In this study, two of dogs died within a few days after a shunt occlusion. In the control group, a lower ICP was observed when compared with that in the hydrocephalus group during the shunt occlusion (PO.001) stage, but not during the shunted stage (3.96 ± 1,78mmHg,p>0.05). ?For the test group (n=10) , before shunt, the brain compliance under a low pressure was 0.288±0.074ml/mmHg, the brain compliance under a high pressure was 0.065±0.008ml/mmHg;after V-P shunt, the brain compliance under a low pressure was 0.263±0.078ml/mmHg, the brain compliance under a high pressure was O.O53±O.O13ml/mmHg;after the shunt occlusion, the brain compliance under a low pressure was 0.300±0.082ml/mmHg, the brain compliance under a high pressure was 0.032dfc0.005rnl/mmHg. Brain compliance at high pressure demonstrated a significant gradual decrease in hydrocephalus group(p<0.05, 0.005, 0.001), but was no significant difference at low pressure. For the control group ( n=5), before shunt, the brain compliance under a low pressure was 0.203+0.05 ml/mmHg, he brain compliance under a high pressure was 0.082+0.017 ml/mmHg;after V-P shunt, the brain compliance under a low pressure was 0.206 + 0.059ml/mmHg, the brain compliance under a high pressure was 0.092 ±0.019 ml/mmHg;after shunt occlusion, the brain compliance under a low pressure was 0.209+0.049 ml/mmHg, the brain compliance under a high pressure was 0.090+0.016 ml/mmHg? ?Under a low pressure, before shunt and after shunt occlusion , the brain compliance of the test group is higher than that of control (p<0.05, p<0.05)? after shunt placement, there was no significant difference between the test group and the control group(p>0.05). Brain compliance measured at high pressure demonstrated a significant gradualdecrease at every measurements (p<0.05,0.01,0.001).Conclusion: (DAfter shunt placement, previously hydrocephalus symptoms and sign got disappear. Shunt occlusion reverses these improvements quickly back to levels present during the untreated stage. ? Brain compliance measured at high pressure demonstrated a significant gradual decrease at the untreated -. shunt and shunt-obstruction stages. The decrease in brain compliance may be one of the factors responsible for the acute pathological changes after the failure of shunt.The third part: The pathological changes and varieties of the number of dopaminergic neuron of periventricle tissues caused byexperimental hydrocephalusResults: ?In contrast with control group, the periventricular tissues of the experimental group developed the following changes: widened fissures, flattened gyri, depressed grey and white matter, twisted hippocampi, prolonged fimbria hippocampi et al. ?The pathological changes were also viewed as the ependyma cells flattened like bug-corroded , the ependyma is discontinued with the structures completedly destroyed. The edema of priventricular tissues is mostly seen in the white matter. The number of the synapsis and other protuberances of the pyramid cells in the deep cortex of the control group is much less than the control group, the former is charactered by enlarged cell nucleus with darkened coloration, the perinuclear cytoplasm was less colored, and the astrocytes together with small glia cells developed reactive hyperplasia and hypertrophy. The endothelial cells swelled and the gaps between them were broadened. The nerve fibers of the callosum were also loosened and stretched. (§) We found that the amount of dopaminergic neuron declined compared to the control group in basic ganglion through immuohistochemical method and the larger of ventrical system, the less dopaminergic neuron could be found.Conclusion: ?We primarily observed the ependyma is discontinued with the structures completely destroyed. The edema of priventrar tissues is mostly seen in thewhite matter. The number of the synapsis and other protuberances of the pyramid cells, and the nerve fibers of the callosum were also loosened and stretched.d)There is the pertinency between the symptoms and the decline of the number of dopaminergic neurons in the basic ganglion of hydrocephalus carmines.
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