James P. McAllister

Morphology of embryonic neostriatal cell suspensions transplanted into adult neostriata

Embryonic neostriatal cell suspensions were transplanted into intact or kainic acid-lesioned neostriata of adult host rats. These transplants survived and were sacrificed at 34-78 days posttransplantation. Nissl and Golgi preparations revealed neurons present within the transplants. Neurons with abundant dendritic spines (Spiny type I) were most frequent, but those with fewer spines (Spiny type II) and smooth dendrites (Aspiny II and III) were also present. These results indicate that neostriatal transplants are populated by the major output and internuncial neurons of the neostriatum.

Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement

As a sequel to our previous descriptions of the pathological changes induced by hydrocephalus in the infantile cerebral cortex, the study presented here has evaluated the effects of surgical decompression on cortical cytology and cytoarchitecture. Hydrocephalus was induced in 14 kittens by the intracisternal injection of kaolin at 4 to 11 days of age. Nine of these hydrocephalic animals received low-pressure ventriculoperitoneal shunts at 9 to 15 days after kaolin injection; these animals were monitored preoperatively and postoperatively by ultrasound and were killed at various postshunt intervals up to 30 days. Five normal or saline-injected animals served as age-matched controls. At the time of shunt placement, the ventricular index confirmed that all recipient animals had attained moderate or severe degrees of ventriculomegaly. Within 3 days after shunt placement, the size of the lateral ventricles had decreased to control levels and was accompanied by rapid and dramatic improvements in behavior and skull ossification. When the animals were killed, gross inspection revealed that about half of the animals exhibited mild to moderate ventriculomegaly, with cortical mantles 50 to 80% their normal thickness. Tissue from frontal (primary motor), parietal (association), and occipital (primary visual) cortical areas was processed for light microscopic analysis. Pyknotic or dark shrunken neurons, which are found typically in hydrocephalic brains, were observed only occasionally in the cortex of shunted animals. Gliosis and mild edema were prevalent, however, in the periventricular white matter. The laminae of the cerebral cortex could be identified in all shunted animals. In those animals with mild residual ventriculomegaly, the entire cortical mantle was somewhat compressed, as evidenced by an increased packing density of neurons. Furthermore, the somata of some neurons were disoriented. Overall, these results indicate that most of the morphological characteristics of the cerebral cortex are preserved after surgical decompression and suggest that ventriculoperitoneal shunts may prevent neuronal damage and/or promote neuronal repair.

Effects of Hydrocephalus and Surgical Decompression on Cortical Norepinephrine Levels in Neonatal Cats

Norepinephrine (NE) changes during hydrocephalus, and the effects of surgical decompression on these changes, were studied using a new model of neonatal hydrocephalus. Kittens 4 to 10 days old received intracisternal injections of a sterile solution of 25% kaolin. Control kittens were injected similarly with sterile injectable saline. Ultrasonography was used to follow the progression of ventriculomegaly and the initial effects of the shunts. A subgroup of hydrocephalic animals was shunted using a cerebrospinal fluid lumbar-peritoneal catheter. Hydrocephalic animals were killed at approximately 25 days of age (16-21 days after kaolin injection). Surgical decompression was performed at 12, 16, and 17 days after kaolin injection; these animals were killed 30 days after the shunts were inserted. Control animals were killed at 29 and 53 days of age, to correlate with the ages of the hydrocephalic and shunted animals, respectively. Cortical samples equivalent to Brodmanns areas 4, 22, and 17 were measured for NE using high-performance liquid chromatography. Hydrocephalus caused NE levels to decrease significantly in all cortical areas. These alterations followed a rostrocaudal gradient in severity, with mean reductions of 65.8, 83.9, and 95.8% in areas 4, 22, and 17, respectively. Partial recovery occurred in animals that received shunts 16 and 17 days after kaolin injection, such that NE reductions of 75.7, 56.2, and 81.6% were noted in areas 4, 22, and 17, respectively. Shunting at 12 days after kaolin injection produced complete recovery in areas 4 and 22, with only a 67.7% decrease in area 17. These results suggest that the projection fibers from the locus ceruleus are damaged by the direct effects of hydrocephalus. Axotomy or neuropraxia of these fibers could result in decreases in NE throughout the cerebral cortex. In addition, there appears to be a period of time during which surgical decompression will allow neuropraxic fibers to recover with partial restoration of NE levels. Earlier insertion of a shunt appears to allow for more recovery than later decompression.

Minimal connectivity between neostriatal transplants and the host brain.

The present study sought to determine if axonal connectivity is established between neostriatal transplants and the host brain during the first two months of graft development. Cell suspensions of embryonic neostriatum were transplanted into the adult rat neostriatum lesioned previously by kainic acid. After 1-2 months, injections of horseradish peroxidase conjugated with wheat germ agglutinin (HRP) were made either within the graft, into adjacent host neostriatum or the host ventral midbrain. In animals with HRP injection sites restricted to the graft no retrograde or anterograde label was found in the host brain. However, both anterograde axon label and retrogradely labelled neurons were found in areas within the transplant but distal to the injection site. Neither ventral midbrain nor host neostriatal HRP injections resulted in any significant anterograde or retrograde label within the graft. These results demonstrate a lack of connectivity between neostriatal grafts and the host brain 1-2 months post-transplantation but an ability of grafted neurons to project to different locations within the transplant. Therefore, transplanted neostriatal neurons develop for the first two months in the absence of normal neostriatal afferent and efferent connections.

Monoamine alterations during experimental hydrocephalus in neonatal rats

The present study was designed to determine the selected monoamine changes that occur during infantile hydrocephalus. Obstructive hydrocephalus was induced in newborn rats by injection of a suspension of kaolin into the 4th ventricle and cisterna magna. Eleven days later, experimental animals and their sham-operated littermate controls were killed and pieces of frontoparietal cortex, neostriatum, cerebellar vermis, and brain stem were processed for high performance liquid chromatography. Grossly, the lateral ventricles were extremely enlarged, the cerebral cortex was thinned, the neostriatum was compressed, and portions of the tectum and cerebellum were vacuolated. Decreases in norepinephrine (71%), dopamine (73%), and serotonin (50%) were observed in the cerebral cortex, neostriatum, and cerebellum, respectively. Brain stem norepinephrine and serotonin were increased 70% and 50%, respectively. These increases may indicate impairment of axonal transport or damage to projections from the locus ceruleus and raphe region. These preliminary results suggest that infantile hydrocephalus causes perturbations in the levels of different monoamines in several brain regions. Such changes may critically influence neuronal function and development, as well as the therapeutic management of hydrocephalus.

Maternal Shunt Dependency: Implications for Obstetric Care Neurosurgical Management, and Pregnancy Outcomes and a Review of Selected Literature

OBJECTIVE Because more women with cerebrospinal fluid shunts are surviving to child-bearing age, neurosurgeons, obstetricians, and other health care professionals require information about the care of these patients, especially during pregnancy and delivery. The purpose of this study was to gather comprehensive data from women with shunts regarding their clinical histories during and immediately after pregnancy. The following questions were addressed. 1) How does maternal shunt dependency influence the course of pregnancies and pregnancy outcomes? 2) What neurosurgical complications characterize this population of patients? 3) What complications of shunt dependency influence obstetric management, including prenatal testing and delivery? METHODS A total of 37 respondents (age, 18-41 yr), accounting for 77 pregnancies, completed a questionnaire providing information on maternal background and medical history, shunt performance during pregnancy, management of delivery, pregnancy outcomes, and unusual complications. RESULTS Fifty-six pregnancies resulted in live births; of these, 47 occurred in women with ventriculoperitoneal shunts. Three women underwent therapeutic abortions, 1 experienced preterm delivery, and 8 experienced 17 miscarriages. Four women experienced seizures during pregnancy, five reported third-trimester headaches, and eight described abdominal pains during the first and third trimesters. Four babies were diagnosed as having congenital defects. Shunt malfunctions and revisions occurred 10 times in 7 women, either during pregnancy or within 6 months after delivery. No acute malfunctions occurred during delivery. Forty-seven cases, representing 84% of all pregnancies, exhibited no shunt malfunctions or revisions. CONCLUSION This study extends previous observations to a larger population of shunt-dependent mothers. The results suggest that maternal shunt dependency entails a relatively high incidence of complications but that proper care of these patients can lead to normal pregnancies and deliveries.

The Effect of Inherited Hydrocephalus and Shunt Treatment on Cortical Pyramidal Cell Dendrites in the Infant H-Tx Rat

The neuronal basis for neurological deficits in infantile hydrocephalus is poorly understood. Changes in the dendritic architecture of pyramidal cells of the auditory cortex have been measured at 21 days after birth in H-Tx rats. Tissue was prepared by the rapid Golgi method from hydrocephalic and control litter-mates, together with hydrocephalic rats with ventriculo-subcutaneous shunts placed at 3-4 days or at 10 days after birth. Layer V pyramidal cells were analyzed quantitatively on a light microscope at a magnification of 250 or 400 x. When compared to control, the hydrocephalic rats had a 30% reduction in the cortical thickness whereas in the shunt-treated rats it was similar to control. For both the apical and the basal dendrites, the distance extended from the soma was reduced in hydrocephalic rats by 49-57%, and the total length of the dendritic trees was decreased by 61 and 77%, respectively. Rats shunt-treated at 3-4 days had small dendrite changes which, in most cases, were not significantly different from control. Rats shunt-treated at 10 days had dendrites which were indistinguishable from untreated hydrocephalic rats. Dendritic branch patterns were also affected; the number and mean length of branch segments were reduced in both the hydrocephalic and the 10-day shunt group, with only small changes in the earlier group. Overall, the basal dendrites were more severely affected than the apical dendrites. It is concluded that infantile hydrocephalus results in severe neuronal abnormalities which can largely, but not completely, be prevented by shunt treatment performed in the early stages.

Minimal connectivity between six month neostriatal transplants and the host substantia nigra.

The present study sought to determine if axonal connectivity is established between 6-month-old neostriatal transplants and the host substantia nigra. Cell suspensions of fetal neostriatum were transplanted into the adult rat neostriatum lesioned previously by kainic acid. Horseradish peroxidase injections into the ipsilateral ventral midbrain labelled the lesion site and the intact neostriatum extensively, but no appreciable anterograde or retrograde label was found within the graft. These results demonstrate a paucity of connectivity between neostriatal grafts and the host brain at a time when other investigators have described transplant-mediated recovery of function.

Quantitative analysis of dendrites from transplanted neostriatal neurons

Dendritic spine density was determined quantitatively in 35-day-old neostriatal transplants and age-matched control tissue. Transplanted spiny I neurons showed significant decreases in spine density and in number of proximal dendrites. These differences may be due to aberrant maturation of transplanted neurons.

Anterograde transport of horseradish peroxidase in the nigrostriatal pathway after neostriatal kainic acid lesions

We used the anterograde transport of HRP to analyze the nigrostriatal pathway after intrastriatal injections of kainic acid. A total volume of 1 microliter kainic acid (3 nM) was injected unilaterally into the neostriatum of adult rats. After 5, 10, or 35 days, HRP was injected into the ipsilateral substantia nigra. Sections stained for Nissl substance revealed that kainic acid damaged as much as three-quarters of the neostriatum. Lesion sites were characterized by gliosis and the absence of neurons. Alternate sections processed for HRP histochemistry and analyzed with bright- and dark-field microscopy revealed labeled axons and terminals in the lesion site. These findings were consistent in all three time periods. Much of the labeling was similar to that seen in neostriatal of control animals. However, the normal homogeneous pattern of the nigrostriatal terminal field was disrupted in all experimental groups, illustrated by changes in some labeling characteristics in the lesion site. These findings provide morphologic evidence for the preservation of much of the nigrostriatal pathway but indicate that some axons and their terminals may be altered after kainic acid injection.