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J P McAllister

Publications and source records attributed to J P McAllister.

At least 19 recordsLinked to original sources
PubMed2006

Gene expression analysis of the development of congenital hydrocephalus in the H-Tx rat.

To discover candidate genes in the pathogenesis of congenital hydrocephalus, gene arrays were utilized to analyze transcripts from the midbrain region of 5-day-old H-Tx rats; these animals develop hydrocephalus due to closure of their cerebral aqueduct between embryonic day 18 and post-natal day 5. Of the 15,924 transcripts assayed, we detected 47 differentially expressed transcripts representing 23 genes and 24 expressed sequence tags (ESTs); 17 transcripts (7 genes and 10 ESTs) were upregulated and 30 (16 genes and 14 ESTs) were downregulated in the hydrocephalic animals relative to control non-hydrocephalic animals. Seven of these genes, Cck, Nfix, Lgals3, Gsta1, Xdh, Tnf, and Tfpi-2, can be linked to hydrocephalus. In addition, 17 genes that displayed altered expression in our study are not currently known to be associated with the presence or development of hydrocephalus. These results indicate that a relatively few number of transcripts were found to be altered in the development of hydrocephalus in this model. This is the first experiment of its kind to identify changes in gene expression in a congenital model of rodent hydrocephalus that are occurring locally in the area surrounding the cerebral aqueduct. Studies are now needed to examine these candidate genes and their cognate proteins to delineate their role in hydrocephalus.

Animals↗
PubMed2002

Prereperfusion flushing of ischemic territory: a therapeutic study in which histological and behavioral assessments were used to measure ischemia-reperfusion injury in rats with stroke.

OBJECT: In ischemic stroke, the ischemic crisis activates a cascade of traumatic events that are potentiated by reperfusion and eventually lead to neuronal degeneration. The primary aim of this study was to investigate a procedure that could minimize this damage by interfering with the interactions between reestablished blood flow and ischemically damaged tissue, as well as by improving regional microcirculation. METHODS: Using a novel hollow filament, the authors flushed the ischemic territory with heparinized saline before vascular reperfusion after occlusion of the middle cerebral artery (MCA). The results demonstrate a statistically significant (p < 0.001) reduction in infarct volume (75%; from 45.3 +/- 3.6% to 11.4 +/- 1.7%, determined with Nissl staining) in rats in which a 2-hour MCA occlusion was followed by a 48-hour reperfusion. Infarction and neuronal degeneration were confirmed using silver staining, which revealed a significantly larger infarct (36.3%, p < 0.05) than that detected with Nissl staining. The long-term neuroprotection of the prereperfusion flushing was also evaluated. This was determined by a series of motor behavior tasks (foot placing, parallel bar traversing, rope and ladder climbing) performed up to 28 days after reperfusion. Motor deficits were found to be significantly ameliorated in animals that underwent the flushing procedure (p < 0.001). In addition, neurological outcome was also improved significantly (p < 0.001) in the same animals. CONCLUSIONS: These results indicate that interaction between reperfusion and the metabolically and biochemically compromised tissue could be interrupted by the prereperfusion flushing procedure, which could lead to a reduction in brain injury from stroke. Mechanical reopening of the cerebral occlusion with local flushing and isolated reperfusion of the regionally injured brain might offer new treatment options for patients with stroke.

Animals↗
PubMed2001

Neuron tolerance during hydrocephalus.

Whether or not neuron death plays a major role in pathophysiology during hydrocephalus is not well known. The goals of this study were to determine if neural degeneration occurred during hydrocephalus, and to determine if neuron tolerance developed during this pathophysiologic procedure.Neural damage as visualized by a sensitive staining technique, silver impregnation, was observed in three experimental groups: (1) adult hydrocephalic rats induced by kaolin injection into the cisterna magna, (2) adult rats with chronic hydrocephalus for 10 weeks subjected to acute forebrain ischemia induced by four-vessel occlusion, and (3) adult rats without hydrocephalus subjected to acute forebrain ischemia. The magnitude of hydrocephalus was also evaluated during this time. In mild or moderate hydrocephalus, little cell death was found. In severe hydrocephalus, axon and neuropil degeneration was extensively distributed, but cell death was still rarely observed. Although some neuron degeneration was found after acute forebrain ischemia in hydrocephalic rats, the extensive cell death in cortical layers III and V, and in hippocampal areas CA1 and CA4 that is commonly observed in the ischemic brain without hydrocephalus, was not seen. This study suggests that neuron death was not a major pathological change in the brain during hydrocephalus, with cerebral ventricles being enlarged during the development of hydrocephalus. Less neuron death in hydrocephalic rats after acute forebrain ischemia suggests that neuronal tolerance to ischemia occurs during hydrocephalus.

Animals↗
PubMed2001

Axonal damage associated with enlargement of ventricles during hydrocephalus: a silver impregnation study.

Motor and cognitive deficits are commonly associated with hydrocephalus. Although the mechanisms responsible for these impairments have not been confirmed, neuronal cell death and axon degeneration may play an important role, and have long lasting consequences on neuronal connectivity. The goal of this study was to determine if neural degeneration occurred during hydrocephalus in structures anatomically related to cognitive motor functioning, namely, the sensorimotor cortex, neostriatum, hippocampus and corpus callosum. Neural damage, as visualized by silver staining, was examined in adult rats 2-10 weeks after obstructive hydrocephalus was induced by kaolin injection into the cisterna magna. In mild or moderate hydrocephalus, mostly occurring 2-6 weeks after kaolin injections, silver-labeled axons were scattered in the white matter of the sensorimotor cortex, corpus callosum, neostriatum, and hippocampus. In severe hydrocephalus, 10 weeks after kaolin injections, axon degeneration was more extensive in these areas, as well as in layers IV through VI of the sensorimotor cortex. Axons in the subiculum and the fimbria were heavily labeled, suggesting damage to hippocampal afferent and efferent fibers. In contrast, neuron cell death was rarely observed at any stage of hydrocephalus. The major pathological change of brain regions involved in motor and learning functions during hydrocephalus is axon degeneration, and this degeneration is correlated with an enlargement of the cerebral ventricles.

Animals↗
PubMed2000

Pathology of the hippocampus in experimental feline infantile hydrocephalus.

Hydrocephalus is responsible for many pediatric neurological deficits presumed to be caused by neocortical pathophysiology. Relatively little is known about the role of non-neocortical CNS structures in this condition. In the present work experimental infantile hydrocephalus produced by intracisternal kaolin injection was studied in a neonate kitten model. The hippocampal formation was processed for electron microscopy, and the neuropil of the CA3 region was examined in untreated, severely hydrocephalic and age-matched normal animals. Both macroscopically and microscopically the thickness of the hippocampus was not decreased. Hippocampal pyramidal neurons were found in varying stages of cytoplasmic densification, and dendritic and axonal processes exhibited hydropic cellular deterioration. The number of synaptic contacts was decreased. However, there was no indication of edematous extracellular space and the ependymal covering of the hippocampus was intact. The macroscopic structural integrity of the hippocampus, as well as the dendritic, axonal and synaptic alterations, suggest that the dark pyramidal neurons are the result of deafferentation, which may have profound effects on learning and memory.

Animals↗
PubMed2000

A brief review of the effects of chronic hydrocephalus on the gonadotropin releasing hormone system: implications for amenorrhea and precocious puberty.

Precocious puberty and amenorrhea have been associated with hydrocephalus, but the pathogenesis has not been determined. Approximately 22 cases of amenorrhea, and a few cases of precocious puberty, have been reported in hydrocephalic patients. Shunt treatment leads to initiation and maintenance of normal reproductive cycles in most cases. An underlying mechanism responsible for reproductive dysfunction may involve the role of gonadotrophin releasing hormone (GnRH). The exact pathway by which hydrocephalus disrupts the hypothalamic GnRH system is unknown. However, compressive forces, ischemia, and impairment of neurotransmitter feedback loops are likely candidates.

Amenorrhea↗
PubMed1999

Decreased c-fos expression in experimental neonatal hydrocephalus: evidence for reduced neuronal activation.

Although neonatal hydrocephalus often results in residual neurological impairments, little is known about the cellular mechanisms responsible for these deficits. The immediate early gene, fos (c-fos), functions as a "third messenger" to regulate protein synthesis and is a good marker for neuronal activation. To identify functional changes in neurons at the cellular level, the authors quantified fos RNA expression and localized fos protein in the H-Tx rat model of congenital hydrocephalus. Tissue samples from sensorimotor and auditory regions were obtained from hydrocephalic rats and age-matched, normal litter mates at 1, 6, 12, and 21 days of age (four-six animals in each group) and processed for immunohistochemical analysis of fos and Northern blot analysis of RNA. At 12 days of age, hydrocephalic animals exhibited significant decreases in the ratio of fos immunoreactive cells to Nissl-stained neurons from both cortical regions, but no statistical differences were noted in fos expression. At 21 days of age, both the ratio of fos immunoreactive cells to Nissl-stained neurons and fos expression decreased significantly. The number of fos-positive neurons decreased in all cortical layers but was most prominent in layers V through VI. This decrease did not appear to be caused by neuronal death because examination of Nissl-stained sections revealed many viable neurons within the areas where fos immunoreactivity was absent. These results suggest that progressive neonatal hydrocephalus reduces the capacity for neuronal activation in the cerebral cortex, primarily in those neurons that provide corticofugal projections, and that this impairment may begin during relatively early stages of ventriculomegaly.

Journal Article↗
PubMed1999

Development and characterization of an adult model of obstructive hydrocephalus.

While hydrocephalus is common in adults its pathophysiology is not fully understood and its treatment remains problematic. Previous animal models have been acute, developmental, or involved non-specific blockage or inflammation and are not suitable for study of chronic adult-onset hydrocephalus. In this study, we describe the development of a canine model which allows basic physiological studies along with diagnostic and treatment procedures via surgical occlusion of the fourth ventricle with a bolus injection of cyanoacrylic gel glue. A total of 26 adult male canine mongrels were used for the induction of chronic hydrocephalus and were monitored for 1-12 weeks post-induction using magnetic resonance imaging (MRI), intracranial pressure measurements, and neurological fitness assessments. Of these, 81% (21/26) developed hydrocephalus that was mild (N = 6), moderate (N = 7), or severe (N = 8). Pressures were mild and transiently elevated, and brain compliance decreased. Clinical symptoms were also mild and transient. This model is unique in its focal obstruction without local compression or general inflammation and should facilitate the study of the pathophysiology and treatment of chronic adult-onset hydrocephalus.

Animals↗
PubMed1998

Differential ventricular expansion in hydrocephalus.

In the large canine model of acquired obstructive hydrocephalus that we have developed recently, computer-assisted 3-dimensional morphometry has been performed on T1-weighted Spin Echo MRI images from adult dogs before and after the induction of hydrocephalus. To date, 7 hydrocephalic animals have been analyzed that survived 7-83 days (median = 54) after receiving injections of cyanoacrylate glue into the anterior fourth ventricle. Measurements were obtained from lateral, 3rd, and 4th ventricles. The volumes of the left and right lateral ventricles were symmetrical before and after induction. Mean lateral ventricle volume increased 424% from a baseline of 0.63 cc to a post-induction value of 3.30 cc (p < 0.01 with unpaired t-test). In contrast, the 3rd ventricle expanded 187% from a mean of 0.15 cc to 0.43 cc (p < 0.05). The combined volume of the lateral and 3rd ventricles increased 369% from a mean of 0.78 cc to 3.69 cc (p < 0.01). Evans' ratios, which are used routinely in the clinical setting, were also obtained from linear measurements of the lateral ventricle width divided by brain width at the level of the foramen of Monro. These values exhibited only a 94% increase from mean baseline ratios of 0.17 to post-induction ratios of 0.33 (p < 0.05). These findings indicate that in mechanically-induced obstructive hydrocephalus the relative expansion of the lateral ventricles is greater than that of the 3rd ventricle. In addition, volumetric measurements of the lateral and 3rd ventricles suggest that the extent of ventriculomegaly is 3-4 times greater than estimated by Evans' ratios.

Animals↗
PubMed1998

The microglial response to progressive hydrocephalus in a model of inherited aqueductal stenosis.

Although gliosis has been reported to be a common and persistent feature in the white matter of hydrocephalic brains, no studies have identified the cell types that characterize this response. Therefore, the present study has employed histochemical methods to evaluate microglial cells in the brains of infant rats with inherited hydrocephalus. This strain of rats acquires hydrocephalus during late fetal stages due to aqueductal stenosis. Tissue from the sensorimotor and auditory cortices of 12- and 21-day-old hydrocephalic and normal H-Tx rats was processed and stained for the lectin microglial marker Griffonia simplicifolia (GSA-IB4). During the progression of hydrocephalus, GSA-positive cells exhibited three changes: (1) Cytologically, the cell bodies were enlarged, and their processes were thicker, longer and more numerous. These changes were most notable in the gray matter. (2) The packing density of GSA-positive cells was either increased or decreased, depending on the age of the animal and the severity of hydrocephalus. (3) Localized clusters of GSA-positive cells were conspicuous in the white matter of 12-day animals with mild hydrocephalus, and in the gray matter of 21-day animals with severe hydrocephalus. These results indicate that the microglial response is initiated during intermediate stages of hydrocephalus, and is not restricted to the periventricular white matter. These changes may signal other pathophysiologic events in the hydrocephalic brain, and demonstrate that microglia constitute one important element in the gliosis that accompanies hydrocephalus.

Animals↗
PubMed1998

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.

Adolescent↗
PubMed1998

Neonatal hydrocephalus. Mechanisms and consequences.

Although hydrocephalus is a multifactorial disorder, the processes responsible for neurologic impairment can be classified into primary and secondary mechanisms. Primary mechanisms include mechanical compression and stretching of brain parenchyma, ischemia and anoxia, cerebral edema, and blood brain barrier dysfunction. These processes lead to secondary mechanisms, which include cytologic and cytoarchitectural alterations of neurons, reduced size and numbers of cerebral microvessels, axonal degeneration and demyelination, and so on. Shunting studies suggest that neuronal cell death may not play a major role until severe stages of hydrocephalus and that some impairments in connectivity can be reversed. Relatively early shunting may alleviate many of the pathologic features of hydrocephalus, but residual impairments in neurotransmitter levels and dependence on anaerobic respiration leave the treated hydrocephalic brain vulnerable to subsequent insults.

Humans↗
PubMed1996

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.

Analysis of Variance↗
PubMed1993

The microstructure of cortical neuropil before and after decompression in experimental infantile hydrocephalus.

Hydrocephalus is a common clinical disorder and responsible for many pediatric neurological deficits. Relatively little is known about the cellular mechanisms of this disorder and less is known about reconstitution of connectivity following ventricular shunt procedures. In the present studies experimental infantile hydrocephalus produced by kaolin injection was studied in a neonate kitten model. The neuropil of the cerebral cortex was examined in hydrocephalic animals and animals which received a ventriculoperitoneal shunt to reduce ventriculomegaly. The brains were processed for Golgi silver impregnation and electron microscopy to study the detailed dendritic and synaptic architecture. The periventricular region of the hydrocephalic animals exhibited increased extracellular space and signs of neuronal degeneration. Components of the deep neuropil (laminae V-VI) were in disarray and surrounded by edematous extracellular spaces. The superficial neuropil (laminae I-IV), in contrast, appeared intact, but detailed examination showed indications of dendritic degeneration. Shunt procedures successfully restored the cortical mantle to near normal thickness. However, Golgi light microscopy and electron microscopy revealed that dendritic appendage morphology was altered. The results are discussed in regard to development of neuronal connectivity following shunt procedures.

Animals↗