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Regional differences in peptide degradation by rat cerebral microvessels: a potential novel regulatory mechanism for communication between blood and brain.

The blood-brain barrier (BBB), composed of the microvessels of cerebral capillary endothelial cells, regulates the passage of peptides into the brain in several ways, mainly by saturable transport or passive diffusion. Here we describe an additional mechanism by which this regulatory function can occur. Cerebral microvessels were isolated from different regions of the brain and incubated with the mu-opiate selective endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) or the opiate-modulating Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2), both tetrapeptides selectively tritiated at the Pro. Degradation was determined by HPLC. For both peptides, the metabolism by microvessels from the cerebral cortex was much greater than that by microvessels from the hypothalamus or pons. For endomorphin-1, the least degradation was in the pons; for Tyr-MIF-1 there was no difference in metabolism by microvessels from the pons or hypothalamus. The results show a novel mechanism at the BBB by which the BBB can selectively regulate the activity of different peptides in different regions of the brain.

Animals↗

An HRP study on cell types and their regional topography within the locus coeruleus innervating the supraoptic nucleus of the rat.

Detailed histochemical studies have been performed on the distribution of various types of horseradish peroxidase (HRP) labeled neurons in the rat dorsal pons with special reference to regional topography within the locus coeruleus (LC) after HRP injections into the nucleus supraopticus (SO). Successful HRP injections into the SO resulted in labeling only in the ipsilateral LC but not in the other structures of the pons. In these cases a few densely labeled multipolar neurons were scattered in both dorsal and ventral divisions throughout the LC. HRP deposition in the hippocampus proper increased significantly the number of labeled neurons in the dorsal division of the ipsilateral LC where a few fusiform neurons in addition to more numerous multipolar ones were labeled. These results strongly suggest that the LC must be the only site of the dorsal pons that innervates the SO, that mainly a part of multipolar neurons may project to the ipsilateral SO, and that regional topography within the LC innervating the SO must be very different from that innervating the hypothalamus. At the present time there remains a possibility that the LC may project to the contralateral SO.

Animals↗

Regional distribution of nicotinic receptors during prenatal development of human brain and spinal cord.

The development of nicotinic acetylcholine receptors (nAChRs) in brains from human fetuses of 4-12 weeks gestational age was studied. The expression of nAChR subunit mRNAs was analyzed using reverse transcriptase-polymerase chain reaction. Expression of alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3 and beta 4 mRNA were all detected in the prenatal spinal cord, medulla oblongata, pons, cerebellum, mesencephalon, subcortical forebrain and cortex during first trimester development. Relative quantification of mRNA showed that the highest levels for alpha 3, alpha 4 and alpha 7 were expressed in the spinal cord, alpha 5 was most abundant in the cortex and beta 3 was highest in the cerebellum. beta 4 seemed to be equally distributed in all regions whereas beta 2 was high in the cortex and cerebellum. A comparison of expression of nAChR subunit mRNAs in the cortex and cerebellum of prenatal and aged (54-81 years) brain showed that mRNA levels for alpha 4, alpha 5, alpha 7, beta 2 and beta 4 were significantly higher in the prenatal cortex and cerebellum than in aged brain, whereas the level of alpha 3 transcript was similar, and beta 3 significantly higher in aged cortex. Specific binding of [3H]-epibatidine to prenatal brain membranes was detected as early as 4-5 weeks of gestation in the spinal cord, medulla oblongata, pons and subcortical forebrain. A positive correlation between gestational age and [3H]-epibatidine and [3H]-cytisine binding was found in several brain regions. The highest specific binding of [3H]-epibatidine and [3H]-cytisine was detected in the spinal cord, pons and medulla oblongata and the lowest in the cortex. Saturation analysis of [3H]-cytisine binding in both prenatal and aged brain were best fit by a model for a single site, whereas binding data for [3H]-epibatidine revealed two classes of binding sites. The early presence of nAChR proteins and gene transcripts shown in the present study suggests an important role for nAChRs in modulating dendritic outgrowth, establishment of neuronal connections and synaptogenesis during development.

Aged↗

The leukemic oncogene tal-2 is expressed in the developing mouse brain.

tal-1 (T-cell acute leukemia-1; also known as SCL) and tal-2 genes belong to a family of basic helix-loop-helix transcription factors and were originally isolated from the breakpoints of chromosomal translocations in human T-cell leukemia cell lines. tal-1 is expressed not only in hematopoietic cells but also in several endothelial structures and the central nervous system during development. On the other hand, the detailed function and the sites of expression of tal-2 have remained obscure. We cloned the tal-2 cDNA from a mouse embryonic cDNA library and examined its expression pattern in the mouse, comparing with that of tal-1. In situ analyses revealed that tal-2 transcripts are detected at embryonic day 12.5 in the following regions; 1) the diencephalon-the zona limitans intrathalamica and the pretectum, 2) the mesencephalon-the tectum, and the anterior and posterior tegmentum, 3) the metencephalon-the isthmus and the anterior pons. In the diencephalon and the mesencephalon, the expression sites of tal-2 gene were similar to those of tal-1, and its expression was stronger than that of tal-1. In the metencephalon, tal-2 expression was observed in the anterior pons, whereas tal-1 transcripts were detected in the entire pons, and showed stronger expression than tal-2. The tal-2 messages were barely detectable in the brain at birth. These results suggest that tal-1 and tal-2 are involved in the development of specific areas of the central nervous system.

Amino Acid Sequence↗

Differential age-related changes in the regional metencephalic volumes in humans: a 5-year follow-up.

We examined changes in the metencephalon of healthy adults who underwent magnetic resonance imaging twice, 5 years apart. The volumes of the cerebellar hemispheres, anterior and posterior vermis, declive-folium-tuber of the vermis, and the ventral pons were measured by operators unaware of subjects' characteristics and the time of scan. The cerebellar hemispheres and the cerebellar vermis, but not the ventral pons, were smaller in older people at both measurements. Significant linear shrinkage was observed in all examined metencephalic regions. Annualized rate of shrinkage was the greatest in the cerebellar hemispheres, somewhat smaller in the vermis, and minimal in the pons. Neither sex differences, nor sex-specific aging trends were found. We conclude that differential age-related shrinkage of the metencephalic structures occurs in healthy adults, but its magnitude differs from cross-sectional estimates.

Adult↗

Brainstem correlates of gustatory similarity in the hamster.

Responses of neurons in the nucleus tractus solitarius (NTS) and parabrachial pons (Pb pons) of the hamster to 10 gustatory stimuli were compared to behavioral similarities among these compounds. Animals were given a conditioned taste aversion to one of the 10 stimuli by pairing it with an induced gastrointestinal illness. Following this procedure, the degree of generalization of the learned taste aversion to each of the other compounds was measured. Behavioral similarity profiles were derived for each stimulus from the similarities in the generalization profiles of each pair of compounds. The across-neuron correlations in the firing rates evoked by these stimuli in the NTS cells corresponded quite well to these behavioral profiles, as did these neural correlations among Pb pontine cells, except for those correlations involving quinine. Sucrose-best cells in the Pb pons are too broadly responsive to account for the behavioral similarity functions for sweet-tasting stimuli, although other best-stimulus categories of cells (NaCl- and HCl-best) showed response profiles quite similar to the behavioral profiles, as did all best-stimulus classes of cells in the NTS.

Animals↗

Acute moderate hyponatraemia and its rapid correction: effects on striatal and pontine ultrastructure in an animal model of the TURP syndrome.

BACKGROUND AND OBJECTIVE: To investigate the effects of moderate hyponatraemia, induced by intravenous application of an electrolyte-free irrigation fluid, as a model of the human transurethral prostate resection syndrome and of its rapid correction by hypertonic saline infusion in rats. METHODS: Experimental animals received irrigation fluid (Purisole SM) 20 mL kg(-1) body weight, intravenously. In one group, hyponatraemia was subsequently rapidly corrected by infusion of hypertonic saline (NaCl 5.85%), while rats of group two were 'sham-corrected' by infusion of a balanced salt crystalloid solution. Plasma sodium concentrations were analysed during and at the end of the experiments. After 10 days, experimental and untreated control animals were killed humanely, fixed by perfusion and the brains were prepared for electron microscopic investigation of myelin sheets and glial cell numbers in the striatum and pons. RESULTS: The myelin appearance was unaltered in experimental groups compared to controls, but glial cell numbers were distinctly altered in the pons but not in the striatum. In the pons, oligodendrocytes were significantly reduced in number upon rapid correction of hyponatraemia, while astrocyte numbers were increased in rats with uncorrected hyponatraemia. CONCLUSIONS: Our electron microscopic data demonstrate that the effects of hyponatraemia and of its rapid correction are multifarious in animals. This may also apply for human patients during transurethral prostate resection.

Animals↗

The results of radiotherapy for brainstem tumors.

OBJECTIVE: This analysis was performed to examine the outcome of adult and pediatric patients with brainstem tumors. METHODS AND MATERIALS: Forty patients with brainstem glioma were evaluated retrospectively. Included were 24 females and 16 males ranging in age from 3 to 81 years (median, 29.5 years). These patients were treated with various combinations of surgery, chemotherapy, and radiotherapy (RT). The length of follow-up in survivors ranged from 0.6 to 20 years (median: 3.2 years, mean: 6 years). Survival rates were calculated with the Kaplan Meier method and differences between survival curves were calculated using the log-rank test. RESULTS: The overall 2 and 5-year survival rates were 44% and 34%, respectively. The median survival time was 19 months. The 5-year survival rate was 54% for patients with tumors outside the pons compared to 21% for those with tumors involving the pons (p = 0.04). The 5-year survival rate was 59% for patients with exophytic tumors as compared to 23% for those with intrinsic tumors (p = 0.05). Patients undergoing subtotal resection had a 5-year survival rate of 53% compared to 28% for those having only a biopsy or no surgical intervention (p = 0.04). None of the other potential prognostic or treatment related factors evaluated [patient age, tumor grade, tumor histology, radiotherapy parameters (including BID fractionation, 3-D treatment planning, or the use of doses > 55 Gy), or the administration of adjuvant chemotherapy] evaluated were associated with patient survival. CONCLUSIONS: Brainstem gliomas generally occur in younger individuals. The survival rates were better for patients with exophytic tumors, those involving sites other than the pons, and tumors amenable to subtotal resection. Improvements in the outcome of patients with brainstem gliomas will require new therapeutic approaches.

Adolescent↗

A novel central pathway links arterial baroreceptors and pontine parasympathetic neurons in cerebrovascular control.

1. We tested the hypothesis that arterial baroreceptor reflexes modulate cerebrovascular tone through a pathway that connects the cardiovascular nucleus tractus solitarii with parasympathetic preganglionic neurons in the pons. 2. Anesthetized rats were used in all studies. Laser flowmetry was used to measure cerebral blood flow. We assessed cerebrovascular responses to increases in arterial blood pressure in animals with lesions of baroreceptor nerves, the nucleus tractus solitarii itself, the pontine preganglionic parasympathetic neurons, or the parasympathetic ganglionic nerves to the cerebral vessels. Similar assessments were made in animals after blockade of synthesis of nitric oxide, which is released by the parasympathetic nerves from the pterygopalatine ganglia. Finally the effects on cerebral blood flow of glutamate stimulation of pontine preganglionic parasympathetic neurons were evaluated. 3. We found that lesions at any one of the sites in the putative pathway or interruption of nitric oxide synthesis led to prolongation of autoregulation as mean arterial pressure was increased to levels as high as 200 mmHg. Conversely, stimulation of pontine parasympathetic preganglionic neurons led to cerebral vasodilatation. The second series of studies utilized classic anatomical tracing methods to determine at the light and electron microscopic level whether neurons in the cardiovascular nucleus tractus solitarii, the site of termination of baroreceptor afferents, projected to the pontine preganglionic neurons. Fibers were traced with anterograde tracer from the nucleus tractus solitarii to the pons and with retrograde tracer from the pons to the nucleus tractus solitarii. Using double labeling techniques we further studied synapses made between labeled projections from the nucleus tractus solitarii and preganglionic neurons that were themselves labeled with retrograde tracer placed into the pterygopalatine ganglion. 4. These anatomical studies showed that the nucleus tractus solitarii directly projects to pontine preganglionic neurons and makes asymmetric, seemingly excitatory, synapses with those neurons. These studies provide strong evidence that arterial baroreceptors may modulate cerebral blood flow through direct connections with pontine parasympathetic neurons. Further study is needed to clarify the role this pathway plays in integrative physiology.

Animals↗

Quantification of benzodiazepine receptors in human brain using PET, [11C]flumazenil, and a single-experiment protocol.

A kinetic method using a multiinjection protocol, positron emission tomography (PET), and [11C]flumazenil as a specific ligand was used to study in vivo the flumazenil-benzodiazepine receptor interactions in the human brain. The model structure is composed of three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The arterial plasma concentration, after correction for metabolites, was used as the input function. The experimental protocol, which consisted of three injections of labeled and/or unlabeled ligand, allowed the evaluation of the five model parameters in various brain regions from a single experiment. In particular, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (KDVR, VR being the volume of reaction) were estimated in five brain regions, including the pons, in which these parameters are identified for the first time (B'max = 4.7 +/- 1.7 pmol/ml and KDVR = 4.4 +/- 1.3 pmol/ml). Due to the large range of measured receptor concentrations, a linear correlation between B'max and KDVR was pointed out (r = 0.88, p < 0.0005) and was interpreted as a linear relationship between B'max and VR, the parameter KD being assumed constant. This result and its concordance with the published data are discussed. Simulation of the usual two-experiment Scatchard analysis, using the pons as a reference region, showed that the bias on the receptor concentration estimates introduced by this method is significant (from 20 to 40%) but can be corrected using an estimate of the receptor concentration in the pons. Furthermore, we propose a new experimental protocol, based on a Scatchard analysis of the PET data obtained with a partial-saturation experiment. This single-injection protocol is entirely noninvasive, and thus the estimation of the benzodiazepine receptor concentration and of the flumazenil affinity is now possible in human patients using a single 1-h experiment without blood sampling.

Adult↗

Ectopic expression of the neural cell adhesion molecule L1 in astrocytes leads to changes in the development of the corticospinal tract.

The cell recognition molecule L1, of the immunoglobulin superfamily, participates in the formation of the nervous system and has been shown to enhance cell migration and neurite outgrowth in vitro. To test whether ectopic expression of L1 would influence axonal outgrowth in vivo, we studied the development of the corticospinal tract in transgenic mice expressing L1 in astrocytes under the control of the GFAP-promoter. Corticospinal axons innervate their targets by extending collateral branches interstitially along the axon shaft following a precise spatio-temporal pattern. Using DiI as an anterograde tracer, we found that in the transgenic animals, corticospinal axons appear to be defasciculated, reach their targets sooner and form collateral branches innervating the basilar pons at earlier developmental stages and more diffusely than in wild type littermates. Collateral branches in the transgenic mice did not start out as distinct rostral and caudal sets, but they branched from the axon segments in a continuous rostrocaudal direction across the entire region of the corticospinal tract overlying the basilar pons. The ectopic branches are transient and no longer present at postnatal day 22. The earlier outgrowth and altered branching pattern of corticospinal axons in the transgenics is accompanied by an earlier differentiation of astrocytes. Taken together, our observations provide evidence that the ectopic expression of L1 on astrocytes causes an earlier differentiation of these cells, results in faster progression of corticospinal axons and influences the branching pattern of corticospinal axons innervating the basilar pons.

Aging↗

Continued in situ DNA fragmentation of microglia/macrophages in white matter weeks and months after traumatic brain injury.

Paraffin-embedded material from the pons of head-injured patients whose disability could be attributed to diffuse traumatic axonal injury, and controls, was identified from the department's archive. The cases were divided into three groups based on survival, viz Group 1 (n = 5) who survived for between 4 and 8 weeks, Group 2 (n = 5) for between 3 and 9 months, and Group 3 (n = 5) who survived for more that 12 months. Sections were stained by the TUNEL (TdT-mediated UTP nick end labelling) technique, and by H&E, LFB/CV and immunohistochemically for astrocytes (GFAP) and microglia/macrophages (CD68). Microscopic abnormalities were mapped onto line diagrams of two levels of the pons and quantitation of the response determined by an eye-piece graticule placed over the medial lemmisci, cortico-spinal and transverse fiber tracts. Data were pooled by region of interest. In the H&E and LFB/CV stained sections, there was variable pallor of staining in ascending and descending fiber tracts due to loss of myelin: within these same tracts there was an astrocytosis and increased numbers of microglia/macrophages compared with controls. In the white matter tracts of the controls, there was on average 1-2 TUNEL+ cells per unit area. In contrast, there were on average 2-16 TUNEL+ cells in the cortico-spinal tracts and in the medial lemnisci of all groups of head-injured patients. CD68+ cells co-located with the TUNEL+, and their number mirrored the TUNEL + staining with on average 16-30 cells per unit area in Group 1, 14-27 cells per unit area in Group 2, and 12-14 cells per unit area in Group 3. There was a statistical association between the TUNEL+ and CD68+ cells. Few changes were seen in the transverse fiber tracts of the pons. These findings indicate that most of the in situ DNA fragmentation occurred in microglia/macrophages in ascending and descending fiber tracts of the brain stem in which by conventional light microscopy there is Wallerian degeneration. However, in addition, a few TUNEL+ oligodendrocyte-like cells were also seen.

Adolescent↗

Neuroanatomical correlates of brainstem coma.

The brainstem tegmentum, including the reticular formation, contains distinct nuclei, each of which has a set of chemical, physiological and anatomical features. Damage to the brainstem tegmentum is known to cause coma, the most radical disturbance of consciousness. However, it has remained unclear which nuclei within the tegmentum are crucial for the maintenance of consciousness in humans. Accordingly, we initiated a retrospective study of MRIs obtained from 47 patients with brainstem stroke. The lesion boundaries were charted on patient MRIs and transferred onto a corresponding series of 4.7 T MRIs obtained from a control brainstem specimen that later was cut on a freezing microtome and analysed histologically. In addition, medical charts and available post-mortem materials were used to obtain relevant clinical and anatomical data to verify the MRI readings in each case. We found that in the 38 patients who did not have coma, brainstem damage either was located outside the tegmentum (n = 29) or produced a very small and unilateral compromise of the tegmentum (n = 9). In contrast, in patients who had coma (n = 9), the lesions in the tegmentum were mostly bilateral (n = 7) and were located either in the pons alone (n = 4) or in the upper pons and the midbrain (n = 5). The maximum overlap territory of the lesions coincided with the location of the rostral raphe complex, locus coeruleus, laterodorsal tegmental nucleus, nucleus pontis oralis, parabrachial nucleus and the white matter in between these nuclei. We also found that four coma subjects developed hyperthermia and died in the absence of any infections. In these cases, the maximum lesion overlap was centred in the core of pontine tegmentum. Our findings suggest that lesions confined to the upper pons can cause coma in humans even in the absence of damage to the midbrain. The findings also point to the brainstem nuclei whose lesions are likely to be associated with loss of consciousness and fatal hyperthermia in humans.

Adult↗

Brain norepinephrine and metabolites after treadmill training and wheel running in rats.

Regional changes in concentrations of brain norepinephrine [NE] and its metabolites after chronic exercise have not been described for exercise protocols not confounded by other stressors. We examined levels of [NE], 3-methoxy-4-hydroxyphenylglycol [MHPG], and 3,4-dihydroxyphenylglycol [DHPG] in the frontal cortex, hippocampus, pons-medulla, and spinal cord after 8 wk of exercise. Male Sprague-Dawley rats (N = 36) were randomly assigned to three conditions: 1) 24-h access to activity wheel running (WR), 2) treadmill running (TR) at 0 degrees incline for 1 h.d-1 at 25-30 m.min-1, or 3) a sedentary control group (C). Levels (nmol.g-1) of [NE], [MHPG], and [DHPG] were assayed by high performance liquid chromatography with electrochemical detection. Planned contrasts (P < 0.05) indicated that exercise training increased succinate dehydrogenase activity (mmol cytochrome C reduced.min-1.g-1 wet weight) in soleus muscle for TR compared with WR or C. [NE] was higher in the pons-medulla and spinal cord for both TR and WR compared with C. [DHPG] was higher in the pons-medulla for TR compared with C, and [MHPG] was higher in the frontal cortex and in the hippocampus for TR compared with C. Our results suggest that treadmill exercise training is accompanied by brain noradrenergic adaptations consistent with increased metabolism of NE in areas containing NE cell bodies and ascending terminals, whereas treadmill running and wheel running are accompanied by increases in levels of NE in the areas of NE cell bodies and the spinal cord, independently of an exercise training effect.

Animals↗

The anterior subtemporal, medial transpetrosal approach to the upper basilar artery and ponto-mesencephalic junction.

OBJECTIVE: To describe and anatomically analyze the amount of exposure provided by an anterior subtemporal, medial transpetrosal approach to access the upper third of the basilar artery, ventral mesencephalon, pons, and posterior cavernous sinus. PATIENTS AND METHODS: The outcomes of six patients who underwent surgical treatment via the anterior subtemporal, medial transpetrosal approach at our institution during the past 2 years were reviewed. The series included three patients with subarachnoid hemorrhage from low-lying basilar apex aneurysms, one patient with intraparenchymal hemorrhage from a pontine cavernous malformation, and two patients with slowly progressive cranial neuropathies secondary to petroclival tumors. Thirty dry temporal bone specimens were also measured to quantify the height of petrous bone resection and added proximal basilar artery exposure. RESULTS: The surgical exposure was greatly enhanced in each instance, allowing each lesion to be treated in a straightforward manner with minimal added morbidity (one trochlear nerve palsy, one worsening of a preexistent oculomotor nerve palsy). Our subsequent morphometric analysis indicates that an additional 1 to 1.5 cm of basilar artery, clivus, and pons exposure over that of a standard anterior subtemporal approach is provided by this technique. CONCLUSION: This approach combines the wide view of the subtemporal approach with the more proximal exposure afforded by a medial petrosectomy. The widened visualization of the ventral pons and mesencephalon minimizes cranial nerve morbidity, greatly facilitates dissection of low-lying aneurysms, and provides proximal basilar artery control that would otherwise be obscured by the petrous ridge.

Adult↗

Transsynaptic degeneration in the inferior olivary nucleus associated with pontine glioblastoma.

A case of glioblastoma arising in the pons of a 14-year-old boy in whom transsynaptic degeneration was found in the inferior olivary nucleus is reported. The tumor occupied most of the pons including the tegmental tract and invaded into the midbrain, medulla oblongata, cerebellar peduncles, thalamus, basal ganglia, and meninges. The right inferior olivary nucleus was devoid of the tumorous lesion, but many neurons were severely vacuolated. An immunohistochemical study using glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), and S-100 protein was performed. GFAP and S-100 protein were positive in the reactive glia of the nucleus and NSE gave a faint reaction in some degenerated neurons. These degenerative changes found in neurons of the inferior olivary nucleus were considered to be transsynaptic degeneration due to the destruction of the tegmental tract at the pons and of cerebellar peduncles by invasive pontine glioblastoma.

Atrophy↗

Reversible alterations of cerebral gamma-aminobutyric acid in pyrithiamine-treated rats: implications for the pathogenesis of Wernicke's encephalopathy.

Treatment of rats with the central thiamine antagonist, pyrithiamine, results in severe neurological symptoms such as loss of righting reflex. Measurement of gamma-aminobutyric acid (GABA) content of brain tissue from symptomatic pyrithiamine-treated (PT) rats revealed significant reductions in thalamus, cerebellum, and pons. GABA content of cerebral cortex, however, was unaltered. Activities of the thiamine-dependent enzyme alpha-ketoglutarate dehydrogenase (alpha KGDH) were reduced in parallel with the GABA changes. On the other hand, activities of the GABA-synthetic enzyme glutamic acid decarboxylase (GAD) remained within normal limits, with the exception of a small but significant decrease in thalamus of symptomatic PT rats. Affinities and densities of high-affinity [3H]muscimol binding sites on crude cerebral membrane preparations from symptomatic PT rats were unchanged. Thiamine administration to symptomatic animals resulted in correction of abnormal righting reflexes and in normalization of decreased GABA levels and reduced alpha KGDH activities in cerebellum and pons. Thalamic GABA levels and alpha KGDH activities, on the other hand, remained significantly lower than normal. These results suggest that the reversible symptoms of pyrithiamine treatment may result from imparied GABA synthesis in cerebellum and pons of these animals. Similar mechanisms may play a role in the pathogenesis of the reversible symptoms of Wernicke's encephalopathy in man.

Animals↗

Posterior hypothalamic and brainstem activation in hemicrania continua.

OBJECTIVE: To determine the brain structures involved in mediating the pain of hemicrania continua using positron emission tomography. BACKGROUND: Hemicrania continua is a strictly unilateral, continuous headache of moderate intensity, with superimposed exacerbations of severe intensity that are accompanied by trigeminal autonomic features and migrainous symptoms. The syndrome is exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that of the trigeminal autonomic headaches and migraine in which the hypothalamus and the brainstem, respectively, have been postulated to play central pathophysiologic roles. We hypothesized, based on the clinical phenotype, that hemicrania continua may involve activations in the hypothalamus, or dorsal rostral pons, or both. METHODS: Seven patients with hemicrania continua were studied in two sessions each. In one session, the patients were scanned during baseline pain and when rendered completely pain free after being administered indomethacin 100 mg intramuscularly. In the other session, the patients were scanned during baseline pain and when still in pain after being administered placebo intramuscularly. Seven age- and sex-matched nonheadache subjects acted as the control group. The scan images were processed and analyzed using SPM99. RESULTS: There was a significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons in association with the headache of hemicrania continua. In addition, there was activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus and the substantia nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation was obvious. CONCLUSIONS: This study demonstrated activations of various subcortical structures, in particular the posterior hypothalamus and the dorsal rostral pons. If posterior hypothalamic and brainstem activation are considered as markers of trigeminal autonomic headaches and migrainous syndromes, respectively, then the activation pattern demonstrated in hemicrania continua mirrors the clinical phenotype, with its overlap with trigeminal autonomic headaches and migraine.

Adult↗