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H J Nauta

Publications and source records attributed to H J Nauta.

At least 37 records · Page 2Linked to original sources

Human nerve growth factor prevents degeneration of basal forebrain cholinergic neurons in primates.

Basal forebrain cholinergic neurons respond to nerve growth factor (NGF), and it has been suggested that the administration of NGF might prevent their degeneration in patients with Alzheimer's disease. One major prerequisite to be fulfilled before the consideration of clinical trials of NGF in patients with Alzheimer's disease is the demonstration that human NGF affects basal forebrain cholinergic neurons in primates. In the present study, we used a recombinant human nerve growth factor (rhNGF), which we previously showed to be active on rat basal forebrain cholinergic neurons, in nonhuman primates with a unilateral transection of the fornix (a well-established model for the induction of retrograde degenerative changes in septal cholinergic neurons). After the lesion, one group of animals received rhNGF and a second group received vehicle solution for 2 weeks. In animals receiving vehicle, the medial septal nucleus ipsilateral to the lesion showed reductions in number (55%) and size of cell bodies immunoreactive for NGF receptor and choline acetyltransferase. In Nissl stains, many cells showed reduced size and basophilia. The rhNGF completely prevented alterations in the number and size of NGF receptor- and choline acetyltransferase-immunoreactive neurons in the medial septal nucleus and reversed atrophy in a subpopulation of large, basophilic medial septal nucleus neurons, as identified by Nissl stains. The effects of rhNGF were identical to those of mouse NGF, which we have previously used in the same primate lesion paradigm. The restoration of the phenotype of injured cholinergic septal neurons by rhNGF in the monkey raises the possibility that this factor may be used to ameliorate acetylcholine-dependent memory impairments that occur in aged nonhuman primates. In concert, results of the present investigation provide critical information for the future use of NGF in patients with neurological disorders that affect NGF-responsive cells in the peripheral and central nervous systems.

Acetylcholinesterase↗

Stereotactic brain biopsy in the diagnosis of malignant lymphoma.

Fifteen patients with cerebral involvement by malignant non-Hodgkin's lymphoma were identified, among more than 200 patients who underwent stereotactic biopsy at The Johns Hopkins Hospital. All but one of these cases were diagnosed accurately by the stereotactic biopsy procedure. In 12 of 14 patients, the material was adequate to classify the lymphoma according to the Working Formulation. Because all but one of the lesions were intermediate or high-grade neoplasms, a diagnosis of lymphoma was often possible by conventional light microscopic examination alone. Monotypic light chain expression was demonstrated by immunohistochemical techniques in six patients, and positivity for B-cell markers was observed in an additional case. In one instance, two stereotactic biopsy specimens were interpreted as being suggestive of lymphoma, but necrosis and inflammation prevented a definitive diagnosis. Nine patients had no known risk factors for cerebral lymphoma, and the diagnosis often was unsuspected clinically.

Adolescent↗

Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey.

NGF, a trophic polypeptide, is necessary for the normal development and survival of certain populations of neurons in the CNS and PNS. In the CNS, cholinergic neurons of the basal forebrain magnocellular complex (BFMC) are prominent targets of NGF. During rat development, NGF increases the activity of ChAT in these neurons. In adult rats with experimental injury of axons in the fimbria-fornix, NGF prevents degenerative changes in axotomized cholinergic BFMC neurons in the medial septal nucleus (MSN). Because the amino acid sequences of NGF and its receptor (NGF-R) are highly conserved across species, we hypothesized that mouse NGF would also prevent degeneration of cholinergic BFMC neurons in nonhuman primates. Therefore, the present study was designed to test whether fimbria-fornix lesions result in retrograde degenerative changes in basal forebrain cholinergic neurons in macaques, whether these changes are prevented by mouse NGF, and whether the protective effect of NGF is selective for cholinergic neurons of the basal forebrain. Following unilateral complete transection of the fornix, animals were allowed to survive for 2 weeks, during which time half of the subjects received intraventricular NGF in vehicle and the other half received vehicle alone. In animals receiving vehicle alone, there was a 55% reduction in the number of ChAT-immunoreactive cell bodies within the MSN ipsilateral to the lesion; loss of immunoreactive somata was more severe in caudal planes of the MSN. Remaining immunoreactive neurons appeared smaller than those in control, unoperated animals. In Nissl stains, there was no apparent loss of basophilic profiles in the MSN, but cells showed reduced size and intensity of basophilia. Treatment with NGF almost completely prevented reductions in the number and size of cholinergic neurons and had a significant general effect in preventing atrophy in basophilic magnocellular neurons of the MSN, though some basophilic neurons in the MSN did not appear to respond to NGF. Adjacent 7-microns-thick sections stained with ChAT and NGF-R immunocytochemistry revealed that these markers are strictly colocalized in individual neurons in the MSN in controls and in both groups of experimental animals. Thus, mouse NGF profoundly influences the process of axotomy-induced retrograde degeneration in cholinergic BFMC neurons in primates. The in vivo effectiveness of mouse NGF on primate BFMC neurons suggests that mouse or human recombinant NGF may be useful in ameliorating the ACh-dependent, age-associated memory impairments that occur in nonhuman primates.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

Treatment of carotid-cavernous sinus fistulas using a detachable balloon catheter through the superior ophthalmic vein.

Four consecutive patients with carotid-cavernous sinus fistulas that could not be treated by the standard techniques of endoarterial balloon occlusion or embolization were successfully treated by advancement of a detachable balloon catheter through the ipsilateral superior ophthalmic vein. Under angiographic monitoring, the balloon was passed into the cavernous sinus, inflated to close the fistula, and detached. Three of the patients had a spontaneous fistula, and one had a traumatic fistula that had previously been trapped unsuccessfully. All patients had complete resolution of symptoms and signs after occlusion of the fistula. There were no intraoperative or postoperative complications. The transvenous approach to the cavernous sinus through the superior ophthalmic vein is a safe, effective treatment of carotid-cavernous sinus fistulas, whether they are direct or dural in nature.

Adult↗

Combining the detachable balloon technique and surgery in imaging carotid cavernous fistulae.

Among 143 carotid cavernous fistulae, 10 cases could not be successfully treated by standard endovascular techniques alone; some form of surgical assistance was required. The circumstances included incomplete closure of the fistula while the internal carotid artery was occluded, failure to occlude the fistula after both arterial and venous endovascular approaches, hairpin loop of the cervical portion of the internal carotid artery, failure of previous trapping procedures, and failure to cure spontaneous carotid cavernous fistulae of the dural type after embolization of the external carotid feeders. These ten patients were cured by combining a surgical procedure and an interventional technique.

Adult↗

Lipomeningioma: report of three cases and review of the literature.

Lipomeningioma is a benign tumor of the meninges that contains mature adipose tissue. It demonstrates fat density on computed tomographic scan and mixed signal intensities on magnetic resonance imaging scan. Although the pluripotential nature of the mesenchymal cell has long been recognized, only a single case with this diagnosis has been documented in the literature to date. Three patients with this diagnosis seen at the Johns Hopkins Hospital during the last two years are presented, and the literature is reviewed.

Aged↗

Intraoperative CT monitoring during stereotactic brain surgery.

This paper reports our experience in performing the entire stereotactic surgical procedure with a CT scanner, which shows that target shifting can occur as the probe approaches the target. Therefore, when sampling of small targets or specific sites within larger targets is desired. CT confirmation of the probe's position ensures that the specific area seen on CT is biopsied.

Adolescent↗

Magnetic resonance planned thalamotomy followed by X-ray/CT-guided thalamotomy.

Magnetic resonance imaging (MRI) is currently the optimal neuroradiologic technique for visualizing the anterior and posterior commissure for defining the AC-PC line. CT is the optimal technique for electrode and probe guidance during stereotactic thalamotomy. Various possibilities of transferring or overlying MRI and CT are outlined which in some future might result in more refined methods of CT-MRI guidance for stereotactic surgery.

Humans↗

Brain stem abscess managed with computed tomography-guided stereotactic aspiration.

The importance of stereotactic aspiration to the successful management of three cases of brain stem abscess is discussed with special reference to the advantages offered over medical treatment alone. Stereotactic aspiration allows evacuation of pus, accurate bacteriological diagnosis, selection of an optimal antibiotic regimen, and instillation of antibiotics directly into the abscess cavity. In two of the three cases described here, the abscess reaccumulated after initial aspiration despite appropriate maximal medical therapy. A repeat aspiration was required before resolution occurred. We conclude that medical management alone is not adequate for some cases of brain stem abscess. There was no morbidity that could be attributed to the procedure, suggesting that the risk of stereotactic aspiration is probably quite low and is likely to be less than the risk of incorrect diagnosis, suboptimal choice of antibiotics, or progression of the lesion despite appropriate maximal medical therapy.

Adult↗

Virchow-Robin space: a path of spread in neurosarcoidosis.

Three cases of documented sarcoid meningoencephalitis were reviewed. Computed tomography (CT) showed enhancing, perivascular, linear, and nodular areas along the subarachnoid space, extending deep into the white matter. In one case the perivascular granulomatous infiltration, which caused small vessel periangiitis, gave rise to a CT pattern closely resembling that of arteriovenous malformation or infarction with gyral enhancement. This infiltrative pattern might be seen in other chronic meningeal processes. The pathophysiology responsible for the unusual CT appearance and the differential diagnosis are discussed.

Adult↗

An animal model for neuron-specific spinal cord lesions by the microinjection of N-methylaspartate, kainic acid, and quisqualic acid.

It has been shown that N-methylaspartate (NMA), kainic acid (KA), and quisqualic acid (QA) can produce preferential neuronal damage in various parts of the striatum, hippocampus, and thalamus with relative sparing of axons in transit. Thus far, the evidence that axons in transit escape destruction has been based largely on histological observations. To test the functional integrity of axons in passage, we made unilateral lesions with these agents in the cervical spinal cord of rats and compared the subsequent functional deficits with those seen after spinal cord hemisections. Observations were made in 14 rats. In each case, a laminectomy at the C6-C7 level was performed under general anesthesia. Animals receiving microinjections of KA, QA, or NMA showed motor and sensory deficits only in the ipsilateral forepaw and remained able to use the hindpaws normally. By contrast, animals undergoing spinal cord hemisection developed obvious motor deficits in the ipsilateral hindpaw in addition to the deficits in the forepaw. Histological observations of the spinal cords confirmed an extensive gray matter destruction with relative preservation of the long tracts in animals injected with KA, QA, and NMA. In addition, it was noted that spinal cord neurons appear relatively less sensitive to KA and more sensitive to QA than neurons in the thalamus, striatum, or hippocampus. The possible application of these findings for the production of dorsal root entry zone lesions will be discussed.

Animals↗

Arterial bolus contrast medium enhancement for computed tomographically guided stereotactic biopsy.

Stereotactic biopsy of deep-seated brain lesions by computed tomography guidance with intravenous contrast medium enhancement is now a well-recognized technique. However, arteriography continues to be the best method for studying the vasculature of such lesions. A method is described here in which a limited arteriography can be incorporated into the computed tomographic technique especially for the purpose of avoiding injury to vessels in stereotactic biopsy procedures. The technique requires that a single 4-mL bolus of contrast medium be injected intraarterially as the computed tomography scan for stereotactic localization is performed. The vessels are thereby seen in the same computed tomographic image as that used for stereotactic localization. The method has these additional advantages: it provides more pronounced contrast medium enhancement; it requires only 4 mL of contrast medium and can therefore be used in patients with renal failure; it can often distinguish crude arterial and venous phases; and lastly, it can be performed with routinely available equipment.

Adolescent↗

Microsurgical anatomy of spinal subarachnoid space.

The anatomy of the spinal subarachnoid space is reviewed with special reference to the work of Key and Retzius, the authors' own cadaver dissections, and experience from operative cases. It appears that despite some variations in the spinal arachnoid anatomy, there are many consistent features that can serve to guide the operating neurosurgeon.

Adult↗

Perikaryal cell labeling in the subthalamic nucleus following the injection of 3H-gamma-aminobutyric acid into the pallidal complex: an autoradiographic study in cat.

Although the subthalamic nucleus is thought to exert a major influence on the corpus striatum output cells, there is little information available on the transmitter or transmitters involved. In a series of autoradiographic experiments in which various different radiolabeled putative transmitter substances were injected separately into the pallidal complex of cats, it was noted that 3H-gamma-aminobutyric acid injection consistently resulted in perikaryal labeling in the subthalamic nucleus. 3H-gamma-aminobutyric acid injection in the lateral part of the external pallidal segment resulted in labeled cells situated laterally in the subthalamic nucleus, while 3H-aminobutyric acid injection in the internal pallidal segment (entopeduncular nucleus) resulted in cell labeling more medially in the subthalamic nucleus. Perikaryal cell labeling was also noted in the lateral putamen following 3H-gamma-aminobutyric acid injection in the external pallidal segment in cats pretreated with systemic amino-oxyacetic acid. No cell groups other than the striatum and subthalamic nucleus could be made to label with 3H-gamma-aminobutyric acid. Furthermore, no perikaryal cell labeling in the subthalamic nucleus was seen to follow injections of 3H-D-aspartate or 3H-serotonin into the pallidal complex. The findings suggest that 3H-gamma-aminobutyric acid, but not aspartate or serotonin, undergoes high affinity uptake and retrograde transport by subthalamo-pallidal neurons. Bearing in mind the many reservations discussed, the observation implies that 3H-gamma-aminobutyric acid may be a transmitter in the subthalamo-pallidal pathway.

Animals↗

A case of Huntington's chorea with unilateral ectopic gray matter.

The authors report a single case of Huntington's chorea associated with a unilateral focus of ectopic gray matter. The patient's symptoms began at age 45 and included typical involuntary jerking movements of all extremities and face. Mental deterioration may have proceeded the choreiform movements. The family history was positive for Huntington's chorea. Pneumoencephalogram showed atrophy of the caudate nuclei bilaterally early in the disease. The patient improved transiently with haloperidol therapy. The major pathologic features included mild generalized cerebral atrophy with marked atrophy of the caudate nuclei and putamen. Within the white matter of the left frontal lobe, there were irregular nodules of ectopic gray matter with an overall diameter of 2 cm. The rarity of either unilateral ectopia or Huntington's chorea alone, makes it impossible to judge if the two lesions might be linked by a common pathologic mechanism. The significance such a linkage might hold is discussed in light of several currently postulate pathologic mechanisms.

Atrophy↗