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Biomedical subjects

H W Blume

Publications and source records attributed to H W Blume.

At least 19 recordsLinked to original sources

Connections of the hippocampal formation in humans: I. The mossy fiber pathway.

The hippocampal formation has been one of the most extensively studied cortical regions in rats, yet little is known about the anatomical connections of the hippocampus in primates, especially humans. With the use of an antibody against the calcium-binding protein, calbindin-D28K, in normal autopsy tissue and the neuronal tracers biocytin or biotinylated dextrans in in vitro slice preparations from tissue removed during surgery for intractable epilepsy, we examined the human hippocampal mossy fiber pathway. The injections of biocytin into the dentate granule cell layer labeled neurons in a Golgi-like manner, revealing the presence of basal dendrites on about 30% of the granule cells. The granule cell axons, the mossy fibers, initially formed a diffuse plexus of fibers in the polymorphic layer before organizing into fiber fascicles in the hilar pyramidal region. These fiber fascicles were much more prominent rostrally than caudally. Within the hilus and proximal portions of the extrahilar CA3 field, the mossy fibers ran through the pyramidal cell layer, and while near the transition to field CA2, the fibers turned superficially and crossed the pyramidal layer to run in the stratum lucidum. All of these features, seen following injections of tracer into hippocampal slices from the brains of epileptics, were confirmed by calbindin-staining of mossy fibers in normal brains. Biocytin-labeled mossy fiber axons revealed two characteristic types of enlargements: small varicosities and larger expansions. The expansions were found throughout the neuropil and were highly irregular, diaminobenzidine-dense profiles that had pleiomorphic modes of attachment to the parent axon. Electron microscopic images of these biocytin labeled expansions revealed that they were large synaptic boutons bearing asymmetric synapses. This study indicates that the human mossy fiber pathway shows some minor deviations from the rodent brain but little difference from monkeys. We argue that these changes mirror a phylogenetic growth of the CA3 pyramidal neurons (subfield CA3c) into the hilus rather than an evolutionary change of the mossy fiber pathway. This growth of subfield CA3c and the increase in mossy fibers running through the pyramidal layer (and a presumed accompanying increase in proximal basal dendritic contacts) may reflect a growing role of the projection from the dentate granule cells to subfield CA3c and from there to field CA1 in the primate hippocampus.

Adult↗

Connections of the hippocampal formation in humans: II. The endfolial fiber pathway.

We investigated the anatomical connections of the pyramidal neurons located within the hilar region of the dentate gyrus of the human hippocampus, neurons which do not have a rodent equivalent. The myeloarchitectural patterns of the human hippocampus indicated the presence of a distinct fiber pathway, the endfolial fiber pathway, in the stratum oriens of the hilus and field CA3. By using the fluorescent lipophilic dye DiI in formalin-fixed human hippocampal tissue, we demonstrated that this is a continuous fiber pathway between the deep hilar region and CA2. This fiber pathway did not enter the fimbria or alveus along the entire distance of the traced pathway and ran exclusively in the stratum oriens of the hilus and CA3. Tracing studies with biocytin in in vitro human hippocampal slices indicated that the hilar and CA3 pyramidal neurons contributed to this pathway. Out distally in field CA3, the long transverse fibers became short and choppy, suggesting that they were beginning to move out of the plane of the tissue slice. Numerous fibers from this pathway were seen crossing the pyramidal layer. Based on comparative studies, we propose that the endfolial fiber system is a component of the hilar Schaffer collateral system in humans. The presence of a significant Schaffer collateral system from the pyramidal neurons in the hilar region would indicate that these neurons are anatomically related to the CA3 pyramidal neurons. Therefore, we suggest the inclusion of the human hilar pyramidal neurons within Lorente de No's field CA3 and, in particular, within subfield CA3c.

Adult↗

128-channel cable-telemetry EEG recording system for long-term invasive monitoring.

A 128-channel cable-telemetry EEG monitoring system has been developed for use on patients undergoing intensive neurodiagnostic monitoring with invasive intracranial electrodes. A unique head mounted preamplifier/multiplexor design allows continuous recording from any combination of intracerebral, subdural, epidural or surface electrodes. A computer is used to delay or buffer all 128 channels by 2 min or more. This computer is connected to a fileserver via a local area network and is used exclusively for data acquisition. Seizure files created by the activation of the seizure/event push button or detected by a second computer containing on-line seizure/spike detection algorithms are written directly on to the fileserver by the acquisition computer. The 128 channels of EEG recorded on the fileserver can then be remotely reviewed on a high resolution graphics terminal, printed out on a laser jet printer, archived or played out on paper, 16 channels at a time on any EEG machine. A time of day signal is also generated by the computer to permit time correlation with a continuous audio/video VCR unit which permits comparison of the EEG and clinical events. This system allows continuous EEG monitoring of extensive multichannel arrays not previously possible with conventional 16-, 32- or even 64-channel systems.

Electroencephalography↗

High resolution EEG output using a laser printer.

With increasing computerization, digitization and complexity of 64- to 128-channel long-term monitoring (LTM), new problems have arisen with data presentation. We describe customized software that allows for high resolution EEG output on a standard laser printer. This system can display from 1 to 128 channels of EEG on standard or legal size paper with freedom to alter both time and amplitude scales as desired. This technique is inexpensive and provides a high resolution rectilinear paper record of selected EEG events that is convenient for review and storage.

Computers↗

Abnormal pulsatile secretion of luteinizing hormone in men with epilepsy: relationship to laterality and nature of paroxysmal discharges.

We compared the pulsatile secretion of luteinizing hormone (LH) between 13 men with clinically and electrographically documented temporal lobe seizures and 8 age-matched controls. Serum for LH measurement was drawn every 15 minutes during 8 hours of EEG telemetry in both groups. The 2 groups did not differ significantly in average mean baseline LH secretion, total LH secretion, or average pulse amplitude. The group with seizures, however, showed a significantly greater (p less than 0.05) variability of baseline LH secretion and pulse frequency. Among the men with unilateral paroxysmal EEG findings, pulse frequency was significantly greater (p = 0.05) with right epileptiform discharges or left slowing (6.4 +/- 0.4) than with left epileptiform discharges or right slowing (3.0 +/- 1.3). The relationship of pulse frequency to the nature and laterality of paroxysmal discharges makes it unlikely that endocrine abnormalities can be attributed to medication alone and strengthens the notion that temporal lobe epileptiform discharges may disrupt hypothalamic regulation of pituitary secretion.

Adolescent↗

Visual neglect during intracarotid amobarbital testing.

The unilateral suppression of hemispheric function by sodium amobarbital may result in hemispatial visual neglect, as measured by performance on a random letter cancellation task. Our study not only investigates this hypothesis but also attempts to identify more precisely the anatomic locus of control for directed attention to extrapersonal space by correlating scanning performance with EEG activity. Forty-eight consecutive patients with epilepsy underwent preoperative intracarotid amobarbital tests. The results indicated that disruption of scanning and contralateral neglect occurred only after right-hemisphere suppression and seemed specifically related to changes in right frontal lobe EEG activity. This pattern of performance held not only for right-handed subjects, but also for those who were left-handed, and even for those who had right-hemisphere language dominance.

Adolescent↗

Alterations of hippocampal acetylcholinesterase in human temporal lobe epilepsy.

Hippocampal sclerosis is the most common pathological finding associated with human temporal lobe epilepsy. Histochemical study with acetylcholinesterase (AChE) staining was used to investigate 7 surgically resected temporal lobes with hippocampal sclerosis from patients with temporal lobe epilepsy. In all 7 specimens, an abnormal but consistent pattern of staining was noted. In the hilum of the dentate gyrus, AChE-rich polymorphic cells were relatively preserved in comparison to the pyramidal neurons. In Ammon's horn, AChE fibers were lost in regions corresponding to the pyramidal cell dropout. AChE fibers were also lost along the inner portion of the molecular layer of the dentate gyrus, yet they were preserved within the outer portions of the molecular layer. These findings provide additional evidence for the relative selectivity of hippocampal pathology in human temporal lobe epilepsy.

Acetylcholinesterase↗

Embolization of solitary spinal metastases from renal cell carcinoma: alternative therapy for spinal cord or nerve root compression.

Four patients with a solitary vertebral metastasis from a renal cell carcinoma presented with acute spinal cord or nerve root compression. Because of the markedly hypervascular nature of the metastases it was decided to palliate the lesions by transarterial catheter embolization. The embolization reduced the venous blood pool within the tumors, resulting in progressive neurological improvement often lasting for 12 weeks or more. With such palliation, surgical decompression may be obviated, postponed, or at least made manageable.

Aged↗

Surgical approaches to epilepsy.

Medically intractable epilepsy may be treated successfully with surgery in a high proportion of patients following appropriate clinical and diagnostic evaluation. Recent technical advances provide more precise diagnostic methods, especially for localizing the areas of seizure origin in the cerebral cortex. The excision of epileptogenic cortex remains the main surgical treatment for partial forms of epilepsy, while commissurotomies are appropriate for some patients with a secondary, generalized type of epilepsy. Limited experience with a variety of stereotaxic lesions and the modality of cerebellar stimulation has not yet provided definite evidence of efficacy of these techniques. Following surgical excisions, two thirds of the patients are significantly improved and over one third become seizure free, with morbidity-mortality rates of less than 0.5%.

Cerebral Cortex↗

Effect of optimization of hemodynamics on fibrinolytic activity and antithrombotic efficacy of external pneumatic calf compression.

External pneumatic calf compression is effective but imperfect for antithrombotic prophylaxis in surgical patients. In preliminary studies, sequential filling of multisegmented leggings with graded pressure decreasing from ankle to knee increased venous flow velocity and wall shear stress, decreased residual venous volume, and enhanced postoperative fibrinolysis more than uniform compression. To determine if improved hemodynamics also increased antithrombotic activity, we performed a prospective randomized trial in neurosurgical patients comparing sequential application of graded pressure with uniform pressure applied to either a segmented bladder or to a single bladder. Deep vein thrombosis was diagnosed by leg scanning and impedance plethysmography and confirmed by phlebography. Venous thrombosis developed in 3 of 45 patients with graded-sequential filling, 6 of 50 with uniform compression-multiple compartments, and 3 of 41 with uniform pressure single bladder (differences not significant). These results suggest either that uniform compression offers all that can be expected of external pneumatic calf compression in prevention of venous thrombosis, or that even if a study with greater statistical power showed graded-sequential filling to be superior, the benefit/cost ratio of the more complex latter system is not likely to be large.

Adolescent↗

Lateral septum-medial hypothalamic connections: an electrophysiological study in the rat.

Participation of both the lateral septum and the medial hypothalamus in similar behavioral and homeostatic functions, combined with anatomical data indicating a modest descending lateral septum projection to medial hypothalamic areas, prompted an investigation of the electrophysiology of lateral septum--medial hypothalamic connections in pentobarbital-anesthetized male Sprague-Dawley rats. Field potentials evoked by lateral septum stimulation were prominent within the hypothalamic ventromedial nucleus: their distribution closely overlapped with amygdala-evoked field potentials. Lateral septum stimulation evoked orthodromic responses from 67% of 800 medial hypothalamic and preoptic neurons (55.5% excitatory, latency 17.5 +/- 0.5 ms; 11.5% inhibitory, latency 19.1 +/- 1.4 ms), including 15 of 31 tuberoinfundibular neurons activated antidromically from the median eminence, 37.4% of cells responded orthodromically to both lateral septum and amygdala stimulation, whereas only 5.8% of cells demonstrated orthodromic responses to both lateral septum and midbrain periaqueductal gray stimulation. These observations suggest that lateral septum neurons influence the excitability of many medial preoptic and hypothalamic neurons, and indicate a convergence of lateral septum and amygdala influences onto 37% of medial hypothalamic cells. In the rat, the lateral septum's influence on adenohypophyseal hormone secretion appears to be mediated indirectly, i.e. through monosynaptic connections with medial hypothalamic tuberoinfundibular neurons.

Amygdala↗

Connections of the hypothalamic paraventricular nucleus with the neurohypophysis, median eminence, amygdala, lateral septum and midbrain periaqueductal gray: an electrophysiological study in the rat.

Extracellular recordings were obtained from 555 paraventricular (PVN) nucleus neurons in pentobarbital-anesthetized male rats. Cells were examined for their spontaneous activity patterns and response to single 1-Hz electrical stimulation of the neurohypophysis, median eminence, amygdala, lateral septum (LS) and midbrain periaqueductal gray (PAG). Neurohypophyseal stimulation evoked antidromic activation from 109 neurons. Among spontaneously active neurohypophyseal neurons, evidence of a recurrent inhibitory pathway usually required pituitary stimulus intensities twice threshold for antidromic activation. Orthodromic excitatory or inhibitory responses followed amygdala and LS stimulation, but not PAG stimulation. The amygdala influence was predominantly inhibitory to 'phasic' (putative vasopressin-secreting) PVN neurohypophyseal neurons. Neurohypophyseal stimulation evoked orthodromic responses from 124 PVN cells; some of these neurons were also responsive to stimulation in other sites. Median eminence stimulation evoked antidromic responses from 37 PVN neurons; some of these cells also displayed phasic activity but no evidence for recurrent inhibition. Twelve cells in this group were also activated antidromically from both the median eminence and the neurohypophysis; collision tests suggest that the median eminence innervation may be an axon collateral of a neurohypophyseal pathway. Amygdala stimulation was inhibitory to some cells in this category. Amygdala, LS and PAG stimulation evoked antidromic activation from a small number of PVN cells, but none of these cells appeared to innervate more than one area, including the neurohypophysis, and none displayed phasic activity. Orthodromic responses were recorded among other PVN neurons after stimulation in these sites; however, PAG stimulation was the least effective stimulation area. These observations provide additional electrophysiological data that confirm efferent PVN connections to all areas tested, afferent connections from amygdala and LS but not PAG, and the possibility for coordinated activity among PVN neurons through local recurrent or common afferent connections.

Amygdala↗

Sensitivity of identified medial hypothalamic neurons to GABA, glycine and related amino acids; influence of bicuculline, picrotoxin and strychnine on synaptic inhibition.

Medial hypothalamic neurons in pentobarbital anesthetized rats were identified by location and response to electrical stimulation of the amygdala, medial preoptic area, midbrain periaqueductal gray and median eminence. Cells were then examined for their sensitivity to microiontophoretic applications of GABA, glycine and 3 related amino acids, i.e. beta-guanidinopropionic acid, delta-aminovaleric acid and beta-alanine. Application of all agents decreased the spontaneous and glutamate or aspartate evoked activity of the majority of neurons in all identified categories. The majority of neurons were more sensitive to beta-guanidinopropionate, delta aminovalerate and GABA than to glycine and beta-alanine. Bicuculline and picrotoxin produced a selective and reversible antagonism of depressions evoked by GABA and GABA-like amino acids whereas strychnine produced a selective and reversible antagonism of depressions evoked by glycine and beta-alanine. Bicuculline and picrotoxin, but not strychnine, were observed to diminish synaptic inhibition evoked by electrical stimulation of several sites when these agents were administered by microiontophoresis and by i.v. injections in convulsive doses. These observations suggest that many medial hypothalamic neurons have both GABA and glycine receptors but that GABA may have the more important role as a neurotransmitter common to afferent or recurrent inhibitory hypothalamic pathways.

Amino Acids↗

Influence of midbrain stimulation on the excitability of neurons in the medial hypothalamus of the rat.

Extracellular action potentials were recorded from 1098 neurons in the medial hypothalamus of pentobarbital anesthetized male rats. Their excitability was analyzed after single 1 Hz stimulation of the midbrain periaqueductal gray (PAG) or adjacent reticular formation. Cells were also examined for their response to median eminence (ME), amygdala, lateral septum (LS) or anterior hypothalamic/preoptic area (AHA/POA) stimulation. Antidromic invasion from midbrain stimulation was recorded from 110 neurons. Eight of these neurons showed features of axon branching and displayed antidromic invasion from both midbrain and amygdala (2 cells) or AHA/POA (6 cells). Many neurons with midbrain projections displayed orthodromic responses to stimulation in the amygdala, but few responded to AHA/POA or LS stimulation. Midbrain stimulation evoked orthodromic responses from 99 medial hypothalamic neurons. Many of these cells also displayed orthodromic responses to amygdala or AHA/POA stimulation, whereas a small number were activated antidromically by stimulation in these sites. None of 42 neurons activated antidromically from median eminence stimulation were responsive to midbrain stimulation. These results provide electrophysiological evidence of reciprocal connections between medial hypothalamic and medial midbrain areas, and indicate that medial hypothalamic neurons with midbrain connections are subject to influences from other extrahypothalamic areas.

Action Potentials↗

Thyrotropin-releasing hormone selectively depresses glutamate excitation of cerebral cortical neurons.

The microiontophoretic application of thyrotropin-releasing hormone causes a selective reduction in neuronal excitation evoked by L-glutamate but not by acetylcholine in rat cerebral cortex. Thyrotropin-releasing hormone has no influence on the activity of acetylcholinesterase or on choline uptake and release from cerebral synaptosomes. This evidence for a selective interaction between a centrally acting peptide and an excitatory amino acid neurotransmitter may indicate a specific locus of thyrotropin-releasing hormone action at glutamate-activated receptor sites.

Acetylcholine↗