Rostral Brainstem Research Articles

Acute traumatic midbrain hemorrhage: experimental and clinical observations with CT.

Traumatic brain stem hemorrhage (TBH) after blunt head impact is an uncommon injury and has historically been associated with high mortality. Retrospective clinical review identified 64 patients with TBH admitted during a 5-year period. Complete imaging and clinical records for 45 of these patients demonstrated that TBH could be categorized into three groups. The most frequent site of hemorrhage, in 31 (69%) of 45 patients (group 1), was the midline rostral anterior brain stem, posterior to the interpeduncular cistern, and this injury was associated with a 71% survival rate. This pattern was also associated with a predominantly anterior site of head and/or face impact. Eight (18%) patients (group 2) had miscellaneous foci of acute brain stem hemorrhage with seven (88%) surviving. Six (13%) patients (group 3) had brain stem hemorrhage associated with transtentorial herniation and brain stem compression, with 100% mortality. Experimental findings in a canine model and clinical results indicate that the anterior rostral midbrain is a common site of TBH and appears to arise from sudden craniocaudal displacement of the brain at impact. Survival is unexpected high with this location of traumatic midbrain hemorrhage.

Neuro‐ophthalmologic signs of AIDS

In 50 hospitalized patients with acquired immunodeficiency syndrome, signs of central eye movement limitation (28 cases) were most common. Peripheral eye movement limitations (18), abnormalities of vision (18), and abnormal spontaneous eye movements (15) occurred with about equal frequency. Meningitis (17), usually due to lymphoma (8) or Cryptococcus (8), was the usual cause of peripheral nervous system involvement, while toxoplasmosis (18) was more common than lymphoma (4) or presumed viral causes (8) in producing CNS dysfunction. The midbrain and pretectal (8) were affected about as often as the pontine tegmentum (9), but rostral brainstem lesions appeared to be the result of toxoplasmosis (4) or lymphoma (3), whereas a viral etiology was the presumed cause of most caudal stem involvement.

Hypothyroidism increases serotonin turnover and sympathetic activity in the adult rat

Adult, male Sprague-Dawley rats underwent surgical thyroidectomy (Tx) or sham surgery. In all three experiments from which data are reported, a 3-week recovery period was allowed. In experiments I and II, baseline measurements of colonic temperature (Tc) and urinary norepinephrine excretion (NE) were obtained, and both variables were monitored daily for the duration of the studies. After baseline measurements, half of each surgical group was given either triiodothyronine (T3) or vehicle injections subcutaneously; in experiment I replacements continued for 1.5 days, while in experiment II T3 replacement continued for 3.5 days. Rats were decapitated at the end of each experiment and serotonin (5-HT) turnover was measured in brainstem. Serotonin turnover in rostral and caudal brainstem was increased with Tx (p less than 0.05). Increased turnover in caudal brainstem was normalized by T3 only in experiment II. Similarly, decreased Tc and elevated NE with Tx were normalized in experiment II but not in experiment I. In experiment III, NE measurements normalized on a creatinine excretion basis indicated that increased NE is evident with Tx, irrespective of normalization procedure. Significant correlations between 5-HT in caudal brainstem and metabolic correlates of sympathetic function, concurrent normalization of NE and 5-HT in caudal brainstem, plus work from other laboratories describing sympathoexcitatory serotonergic neurons located in the caudal brainstem suggest that the central and peripheral changes in the hypothyroid rat are causally related.

Activity of hippocampal extract on development of [3H]5-HT high-affinity uptake in dissociated microcultures

Specific and localized lesions of the 5-HT fibers in the hippocampus induce homotypic collateral sprouting and enhance serotonergic fiber outgrowth from adult neurons and transplanted fetal tissue. In this study, hippocampal extracts were prepared and applied to primary cultures of fetal serotonergic neurons. The effects of plating density and serum additives were examined. The growth of the serotonergic neurons in the rostral brainstem dissociated cultures were estimated by measuring the specific uptake of [3H]5-HT. The results indicate the presence of a trypsin-sensitive factor which is active when prepared fresh at dilutions up to 110,000. The factor is higher in hippocampus than cerebellum. Young male tissue contained more activity than either female or aged hippocampus. Although both positive and negative effects are described, higher dilutions of factor (11,000) were generally stimulatory in high density cultures while lower dilutions (110) were inhibitory in low density cultures. Specific removal of 5-HT hippocampal afferents with fornix-fimbria microinjections of 5,7-dihydroxytryptamine resulted in an initial loss of activity (2 days and 2 weeks) followed by an enhanced activity (2 months) compared to normal hippocampal extract. Several possibilities are discussed as to the identity of the serotonergic growth factor from hippocampal supernatant.

Directed early axonal outgrowth from retinal transplants into host rat brains

Axons from retinae transplanted to the brain stem of neonatal rats exhibit two patterns of outgrowth that can be experimentally uncoupled from each other depending upon the location of the graft. Retinae placed close to the surface of the rostral brain stem (as much as 5 mm from the tectum) emit axons that project toward the superior colliculus along the subpial margin of the rostral brain stem. In contrast, axons from grafts embedded deep within the midbrain parenchyma project through the neuropil directly to the overlying superior colliculus, as long as the retina is within about 1 mm of the tectal surface. The present study shows that, as long as the retina is located outside the superior colliculus, and regardless of whether the axons derive from grafts in subpial or intraparenchymal locations, the earliest projections are oriented towards the superior colliculus. We have also found, however, that axons from retinae transplanted directly onto the superior colliculus can form projections that extend along the subpial margin away from the tectum. There are several major conclusions that may be drawn from these observations. First, the final tectopetal, transplant-derived projection does not result from the reorganization of an initially random outgrowth but is directed from the start toward an appropriate region of termination. Second, it appears that the interaction of retinal axons with a primary target alters the ability of the growth cone to respond to directional cues along the optic tract. Thus, although adding support to the proposal that optic axons attain the superior colliculus through an interaction involving substrates distributed along the optic tract and diffusible factors originating in the target region, it is increasingly clear that such interactions are likely to be complex and hierarchical.

Proximity as a factor in the innervation of host brain regions by retinal transplants

Embryonic mouse retinae transplanted to a variety of locations within the rostral midbrain of neonatal rats exhibit selective innervation of host visual nuclei when studied at maturity. Some of these nuclei (superior colliculus, nucleus of the optic tract, dorsal terminal nucleus) usually receive extensive transplant projections, others are innervated partially (dorsal division of the lateral geniculate nucleus, olivary pretectal nucleus, medial terminal nucleus), while a few (ventral division of the lateral geniculate nucleus, suprachiasmatic nucleus, intergeniculate leaflet) are not innervated at all. The selectivity of this innervation is largely independent of the transplant's position within the rostral brainstem, while the density of innervation of individual nuclei depends in part upon the proximity of the transplant to the nucleus and upon whether the host retinal projection to that nucleus is present or absent. These findings provide a foundation for further studies of the behavioral capabilities of retinal transplants, for developmental studies of factors responsible for the establishment of normal neural projections, and for examination of the immunological consequences of transplantation.

Non‐missile head injury: report of a patient surviving for 6 years

A female patient with non-missile head injury is described. She showed slight improvement in her level of consciousness, and survived for 6 1/2 years after injury. At autopsy, the white matter lesions were localized rather than diffuse in distribution. In addition to lesions in the corpus callosum, anterior commissure and dorsolateral quadrant of the rostral brain stem, those in the parasagittal cerebral white matter, and in the hilus of the dentate nucleus and superior cerebellar peduncle were considered to be due to primary axonal injury. A cavity in the frontal white matter was remarkable in that there was no evidence to indicate expansion of the lesion due to haemorrhage. These features suggested that the injurious physical forces had acted parallel to the direction of the axons.

Functional organization within the medullary reticular formation of intact unanesthetized cat. II. Electromyographic activity evoked by microstimulation

1. The present study has examined the detailed organization of the medullary reticular formation (MRF) as revealed by microstimulation (33-ms trains of 0.2-ms duration pulses at 330 Hz and 35 microA or less) in the intact, chronically implanted, unanesthetized cat. Stimulus-locked electromyographic (EMG) responses were recorded from flexors and extensors of each of the four limbs, as well as bilaterally from muscles of the neck and back, during stimulation of the same 592 loci that formed the basis of the preceding article. 2. The thresholds of the responses were different for each group of muscles, with, on the average, the neck muscles being activated at the lowest range of currents, 13.8-16.5 microA; forelimb muscles at 16.9-17.9 microA; back muscles at 25.4-25.7 microA; and hindlimb muscles at 21.1-25.7 microA. 3. Whereas stimulation within the MRF evoked movement of the head only to the stimulated side (preceding article), analysis of the EMG responses showed there was frequently bilateral activation of the neck muscles. Similarly, even though stimulation produced predominantly ipsilateral elbow flexion and contralateral elbow extension, most loci caused cocontraction of antagonistic muscles at these joints. Cocontraction was also frequently observed for the hindlimbs. Reciprocal activation of antagonistic muscles was less frequent but was observed in the ipsilateral forelimb as well as in both hindlimbs; it was never observed in the contralateral forelimb. 4. Although excitatory responses were observed from widespread regions for all of the muscles under study, those regions of the MRF that evoked the strongest responses in each muscle showed a large degree of segregation. Muscles of the ipsilateral forelimb were most strongly activated from the rostrodorsal MRF, whereas muscles of the contralateral forelimb were most strongly effected by stimulation caudoventrally. Muscles of the hindlimbs were more strongly activated from the rostral brain stem, although with some exceptions. Responses in axial muscles were evoked from widespread regions of the brain stem but were concentrated further caudally than were the limb muscles. 5. Excitatory responses were much more prevalent than inhibitory responses and were evoked from all regions of the MRF, including the most caudal and ventral areas. The shortest latency responses in each track were, on the average, as follows: 6.6-8.8 ms for the neck; 11.2-13.4 ms for the forelimbs; 13.8-14.2 ms for the back; and 15.9-17.2 ms for the hindlimbs. Inhibitory responses were also evoked from widely distributed regions, which were intermingled with those loci evoking excitatory responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Anatomical and functional recovery folloing spinal cord transection in the chick embryo

Following complete transection of the thoracic spinal cord at various times during embryonic development, chick embryos and posthatched animals exhibited various degrees of anatomical and functional recovery depending upon the age of injury. Transection on embryonic day 2 (E2), when neurogenesis is still occurring and before descending or ascending fiber tracts have formed, produced no noticeable behavioral or anatomical deficits. Embryos hatched on their own and were behaviorally indistinguishable from control hatchlings. Similar results were found following transection on E5, an age when neurogenesis is complete and when ascending and descending fiber tracts have begun to project through the thoracic region. Within 48 h following injury on E5, large numbers of nerve fibers were observed growing across the site of transection. By E8, injections of horse-radish peroxidase (HRP) administered caudal to the lesion, retrogradely labelled rostral spinal and brainstem neurons. Embryos transected on E5 were able to hatch and could stand and locomote posthatching in a manner that was indistinguishable from controls. Following spinal cord transections on E10, anatomical recovery of the spinal cord at the site of injury was not quite as complete as after E5 transection. Nonetheless, anatomical continuity was restored at the site of injury, axons projected across this region, and rostral spinal and brainstem neurons could be retrogradely labelled following HRP injections administered caudal to the lesion. At least part of this anatomical recovery may be mediated by the regeneration or regrowth of lesioned axons. Although none of the embryos transected on E10 that survived to hatching were able to hatch on their own, because several sham-operated embryos were also unable to hatch, we do not attribute this deficit to the spinal transection. When E10-transected embryos were aided in escaping from the shell, they were able to support their own weight, could stand, and locomote, and were generally comparable, behaviorally, to control hatchlings. Repair of the spinal cord following transection on E15 was considerably less complete compared to embryos transected on E2, E5, or E10. However, in some cases, a degree of anatomical continuity was eventually restored and a few spinal neurons rostral to the lesion could be retrogradely labelled with HRP. By contrast, labelled brainstem neurons were never observed following E15 transection. E15 transected embryos were never able to hatch on their own, and when aided in escaping from the shell, the hatchlings were never able to stand, support their own weight or locomote.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuropathological findings in a suspected case of childhood schizophrenia

The ventral tegmental area (VTA) is the major dopaminergic (DA) center responsible for the innervation of the prefrontal cortex, nucleus accumbens, and entorhinal region. These areas have been causally implicated in schizophrenia. Thus, the existence of brainstem pathology could explain many of the previously reported findings in schizophrenic (SC) patients. The authors focus on uncovering brainstem abnormalities in schizophrenia by studying the autopsied material of a patient having an early onset of symptomatology. The patient was evaluated at the age of 10 years for manneristic behavior, a speech disorder, and violence. Prominent auditory hallucinations became apparent years later. His mental status and ability for self-care steadily deteriorated until he succumbed to pneumonia at age 22. Microscopic examination of the brain showed central chromatolysis of neurons and mild gliosis in a restricted distribution of the brainstem and thalamus. Cell loss and cytoarchitectural disruption were evident in the frontal lobes, prepyriform cortex, and entorhinal region. The neuropathological changes were interpreted as a chronic derangement in the function of neurons of the rostral brainstem tegmental area and medial thalamus with secondary involvement of their terminal projection sites.

Cure of a man with solitary abscess of the brain-stem

A 25-year-old man with lung abscess and signs of an abscess in the rostral brain-stem was cured by large doses of antibiotics and stereotactic aspiration of the abscess.

Induction of target-directed optic axon outgrowth: Effect of retinae transplanted to anophthalmic mice

In previous work using neural transplants ( Hankin and Lund, 1987) we demonstrated two basic components of optic axon outgrowth in the mammalian retinotectal system: one category of outgrowth utilizes the subpial margin of the rostral brain stem as a preferential substrate (as do normal retinotectal axons); the other type of outgrowth, from retinae embedded deep within the midbrain parenchyma, is distance-dependent and highly target-oriented, but shows little apparent substrate specificity. One explanation for this directed outgrowth is that it is in response to a diffusible factor emanating from cells in the superior colliculus. In the present study we use congenitally anophthalmic mice as recipients for retinal transplants to test whether prior optic innervation of the superior colliculus plays a role in establishing either component of outgrowth. We show that outgrowth along the subpial pathway from a graft placed on the surface of the brain stem can take place in the absence of prior innervation of the superior colliculus. The target-directed outgrowth exhibited by embedded grafts only occurs if the tectum is also innervated by a second graft placed on the surface of the brain stem. It is proposed that tectal cells produce a factor in response to optic innervation and that this directs the growth patterns of embedded grafts. This suggests that optic innervation is a necessary prerequisite for the superior colliculus to produce the proposed diffusible chemotropic signal. In normal development such a factor could function to improve the efficiency of target-finding by later growing optic axons, but it might serve a quite different role, encouraging branching and trophic maintenance of the optic pathway once it has reached the tectum.

Precortical filtering and selective attention: An evoked potential analysis

Attention-related changes in the human auditory brainstem response and the short-latency somatosensory evoked potential (SLSEP) were demonstrated in separate experiments. In Experiment 1, ABRs were recorded during conditions in which subjects awaited the presentation of either auditory or somatosensory target stimuli. In Experiment 2, median nerve SLSEPs were recorded in a similar task context. Analyses of ABR and SLSEP component amplitudes and latencies revealed that the auditory nerve (wave II) and rostral brainstem (wave V) components of the ABR, and the cervical component (N12) of the SLSEP, were facilitated when attention was directed toward stimuli that were presented in the same sensory modality and receptive field as the EP-eliciting stimuli. These results suggest that central mechanisms can modulate the transmission of auditory and somatosensory information at an early, precortical stage and that these mechanisms play a role in auditory and somatosensory selective attention.

Areal Distributions of Cortical Neurons Projecting to Different Levels of the Caudal Brain Stem and Spinal Cord in Rats

Distributions of corticospinal and corticobulbar neurons were revealed by tetramethylbenzidine (TMB) processing after injections of wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) into the cervical or lumbar enlargements of the spinal cord, or medullary or pontine levels of the brain stem. Sections reacted for cytochrome oxidase (CO) allowed patterns of labeled neurons to be related to the details of the body surface map in the first somatosensory cortical area (SI). The results indicate that a number of cortical areas project to these subcortical levels: (1) Projection neurons in granular SI formed a clear somatotopic pattern. The hindpaw region projected to the lumbar enlargement, the forepaw region to the cervical enlargement, the whisker pad field to the lower medulla, and the more rostral face region to more rostral brain stem levels. (2) Each zone of labeled neurons in SI extended into adjacent dysgranular somatosensory cortex, forming a second somatotopic pattern of projection neurons. (3) A somatotopic pattern of projection neurons in primary motor cortex (MI) paralleled SI in mediolateral sequence corresponding to the hindlimb, forelimb, and face. (4) A weak somatotopic pattern of projection neurons was suggested in medial agranular cortex (Agm), indicating a premotor field with a rostromedial-to-caudolateral representation of hindlimb, forelimb, and face. (5) A somatotopic pattern of projection neurons representing the foot to face in a mediolateral sequence was observed in medial parietal cortex (PM) located between SI and area 17. (6) In the second somatosensory cortical area (SII), neurons projecting to the brain stem were immediately adjacent caudolaterally to the barrel field of SI, whereas neurons projecting to the upper spinal cord were more lateral. No projection neurons in this region were labeled by the injections in the lower spinal cord. (7) Other foci of projection neurons for the face and forelimb were located rostral to SII, providing evidence for a parietal ventral area (PV) in perirhinal cortex (PR) lateral to SI, and in cortex between SII and PM. None of these regions, which may be higher-order somatosensory areas, contained labeled neurons after injections in the lower spinal cord. Thus, more cortical fields directly influence brain stem and spinal cord levels related to sensory and motor functions of the face and forepaw than the hindlimb. The termination patterns of corticospinal and corticobulbar projections were studied in other rats with injections of WGA:HRP in SI.(ABSTRACT TRUNCATED AT 400 WORDS)

Brainstem afferents to the tuberomammillary nucleus in the rat brain with special reference to monoaminergic innervation

Monoaminergic innervation of a histamine-producing cell group, the tuberomammillary nucleus in the posterior hypothalamus, was investigated in the rat by light and electron microscopic immunohistochemical techniques. Immunohistochemical staining of sections of the posterior hypothalamus was demonstrated afferent fibers immunoreactive to tyrosine hydroxylase in ventral and medial subgroups of the tuberomammillary nucleus afferent fibers immunoreactive to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenyletanolamine-N-methyltransferase (PNMT), and serotonin (5-HT). TH- and DBH-immunoreactive fibers were similar and were evenly and densely distributed throughout the tuberomammillary nucleus. Fibers stained with 5-HT antibodies were also present throughout the tuberomammillary nucleus but exhibited the densest labeling in the dendritic layer adjacent to the glia limitans in the ventral subgroup. Innervation by PNMT-immunoreactive axons was sparse. Electron microscopic analysis of TH-, DBH-, and 5-HT-immunoreactive fibers in the tuberomammillary nucleus revealed vesicle-containing terminal boutons, which formed synapses with dendrites of varying size. Synaptic contacts with nerve cell bodies were not found. Retrograde transport of the fluorescent dye Fast Blue injected into the tuberomammillary nucleus, combined with immunofluorescent staining with anti-TH, anti-DBH, anti-PNMT, and anti-5-HT antibodies, showed that monoaminergic input to the tuberomammillary nucleus originated mainly from the adrenergic and noradrenergic cell groups C1-C3 and A1-A2, respectively, and from the serotoninergic cell groups B5-B9 as designated by Dahlström and Fuxe ('65). Few double-labeled neurons were found in the nucleus locus coeruleus and the dopaminergic cell groups of the rostral brain stem. The present findings suggest that the activity of the histamine-producing neurons of the tuberomammillary nucleus is influenced by monoaminergic neurons in the ventrolateral and dorsomedial medulla oblongata and the raphe nuclei of the rostral brainstem.

Effect of trigeminal subnucleus caudalis cold block on the cerebrovascular-evoked responses of rostral trigeminal complex neurons

The technique of reversible cold block was used to explore the possibility that the trigeminal subnucleus caudalis (Vc) influences the responses of rostral trigeminal brainstem nuclear complex (TBNC) neurons to stimulation of the cerebrovasculature. Reversible cold block of Vc was found to abolish totally the responses of many rostral TBNC neurons to stimulation of the cerebrovasculature. The remaining neurons were not affected by the cold block. These data suggest that some rostral TBNC neurons may receive an indirect input from the cerebrovasculature via Vc while other rostral TBNC neurons receive a direct input from the cerebrovasculature.

Surgical excision of a cavernous hemangioma of the rostral brain stem

Surgical excision of a cavernous hemangioma of the rostral brain stem

Surgical excision of a cavernous hemangioma of the rostral brain stem: case report.

A 23-year-old pregnant woman presented with sudden diplopia, ataxia, hemiparesis, and headache secondary to a brain stem hemorrhage. Magnetic resonance imaging (MRI) revealed a hematoma associated with a probable cavernous hemangioma of the rostral brain stem. In this report, we discuss the MRI findings leading to the preoperative diagnosis, as well as the surgical techniques involved in the successful resection.

A new model of brainstem ischemia in dogs.

A new model of brainstem ischemia in dogs is described. The perforating arteries arising from the posterior cerebral arteries as far as the bilateral junctions with the posterior communicating arteries were occluded using a subtemporal approach to the region of the interpeduncular cistern. Infarction of the posterior thalamus, subthalamus, midbrain, and upper pons was consistently produced. The dogs survived for greater than 1 week while exhibiting such clinical symptoms as disturbance of consciousness, tetraparesis, oculomotor paralysis, respiratory abnormalities, bradycardia, and arrhythmia. The clinical features and extent of infarction observed in this model closely resemble those of rostral brainstem infarction in human stroke. The model may be useful in studying the pathophysiology of brainstem ischemia.

Cholinergic and non-cholinergic projections from the upper brainstem core to the visual thalamus in the cat.

The projections of cholinergic and non-cholinergic neurons of the rostral brainstem reticular formation to the visual thalamic nuclei (dorsal lateral geniculate - LG, lateral posterior - LP, and perigeniculate - PG) were studied in cat by using the retrograde transport of horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) combined with choline acetyltransferase (ChAT) immunohistochemistry. After thalamic injections, less than 10% of all retrogradely labeled neurons in the upper brainstem reticular core were located at most rostral (perirubral) levels where there are virtually no cholinergic elements. Approximately 75-80% of all HRP-positive neurons in the reticular formation were found between stereotaxic planes anterior 1 and posterior 2, in the peribrachial (PB) area of the pedunculopontine nucleus and in the laterodorsal tegmental (LDT) nucleus. The brainstem afferents to LG and PG thalamic nuclei essentially derive from PB neurons, with a small contribution from LDT cells, whereas the LP thalamic nucleus receives massive inputs from both PB and LDT brainstem nuclei. Of all HRP-positive elements visualized in the PB nucleus after an LG or a PG injection, 87% and 73%, respectively, were also ChAT-positive. Of all HRP-positive elements in the PB and LDT nuclei after an LP injection, 82% and 92%, respectively, were also ChAT-positive. The numbers of labeled neurons in the contralateral brainstem reticular nuclei reach 30% to 50% of the numbers found in the ipsilateral reticular formation. These findings reveal the existence of a prominent cholinergic projection from the brainstem reticular formation to the visual thalamic nuclei. Such a chemospecific projection is probably involved in phasic and tonic events of activated behavioral states.