Brainstem

The functional region known as the brainstem consists of the midbrain, and the pons and medulla of the hindbrain. It is continuous with the spinal cord and serves as an important connection between the brain and spinal cord because all sensory and motor pathways pass through it. The brainstem consists of numerous neuronal clusters or centers, each of which controls vital, life-supporting processes. 

The medulla contains control centers for subconscious, involuntary functions, such as cardiovascular activity, respiration, swallowing, and vomiting. The primary function of the pons is to serve as a relay for the transfer of 

The spinocervical tract terminates before reaching the brainstem and will therefore be included in this section. Other somatosensory pathways will be included in the sections below. 

In addition to cochlear primary afferents (see above), other nerve terminal populations in the auditory system have been subjects for analysis with Glu immunolabeling. Grandes and Streit (1989) examined calyces of Held (originating from the contralateral ventral cochlear 

Similar to other projections from the cerebellar nuclei (except those to the inferior olive which are GABAergic), terminals of cerebellar origin in the red nucleus are enriched in Glu (Schwarz and Schmitz, 1997 Fig. 5). Enrichment of Glu has also been detected in terminals in the oculomotor nucleus originating from the abducens and ventral lateral vestibular nuclei (Nguyen and Spencer, 1999 Fig. 5). 

An extensive review of the chemoarchitecture and anatomy of the cerebellum was published in a recent volume of the Handbook Series (Voogd et al., 1996). This volume should be consulted for a complete bibliography. Another recent review is that of Ottersen and Walberg (2000). 

The major afferent pathways to the cerebellar cortex are the mossy and climbing fiber systems. Climbing fibers establish direct contact with the Purkinje cells, whereas the mossy fibers influence the Purkinje cells indirectly, through the granule cell-parallel fiber system. The excitatory nature of each of these systems (including the parallel fibers) is well-established (Ito, 1984) and several lines of evidence point to Glu as their likely transmitter (Fig. 6). 

The mesencephalon, or midhrain, serves as a bridge between the higher areas of the brain (cerebrum and diencephalon) and the brainstem. The brainstem consists of the pons and the medulla oblongata. In addition to serving as a pathway between the higher brain and spinal cord, the midbrain and brainstem are the locations of centers responsible for controlling respiration and cardiovascular function (vasomotor center). 

The reticular formation is also located in the midbrain and brainstem. The reticular formation is comprised of a collection of neurons that extend from the reticular substance of the upper spinal cord through the midbrain and the thalamus. The reticular formation monitors and controls consciousness and is also important in regulating the amount of arousal or alertness in the cerebral cortex. Consequently, CNS drugs that affect the arousal state of the individual tend to exert their effects on the reticular formation. Sedative-hypnotics and general anesthetics tend to decrease activity in the reticular formation, whereas certain CNS stimulants (caffeine, amphetamines) may increase arousal through a stimulatory effect on reticular formation neurons. 

The cerebellum lies posterior to the brainstem and is separated from it by the fourth ventricle. Anatomically it is divided into two hemispheres, each consisting of three lobes (anterior, posterior, and flocculonodular). The function of the cerebellum is to help plan and coordinate motor activity and to assume responsibility for comparing the actual movement with the intended motor pattern. The cerebellum interprets various sensory input and helps modulate motor output so that the actual movement closely resembles the intended motor program. The cerebellum is also concerned with the vestibular mechanisms responsible for maintaining balance and posture. Therapeutic medications are not usually targeted directly for the cerebellum, but incoordination and other movement disorders may result if a drug exerts a toxic side effect on the cerebellum. 

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Glonidine. Clonidine decreases blood pressure, heart rate, cardiac output, stroke volume, and total peripheral resistance. It activates central a2 adrenoceptors ia the brainstem vasomotor center and produces a prolonged hypotensive response. Clonidine, most efficaciously used concomitantly with a diuretic in long-term treatment, decreases renin and aldosterone secretion. 

Dia2epam [439-14-5] (60) and clona2epam [1622-61 -3] (61) suppress cough induced by electrical stimulation of the lower brainstem of cats (90). Clona2epam and dia2epam adrninistered intravenously are about thirty-five times and six times more potent than codeine, respectively. Nevertheless, the compounds have not been widely used as antitussives in humans. Dia2epam is used in the treatment of anxiety, and clona2epam as an anticonvulsant. 

ALS is a disorder of the motor neurons and the cortical neurons that provide their input. The disorder is characterized by rapidly progressive weakness and muscle atrophy. Most affected patients die of respiratory compromise and pneumonia after 2 to 3 years. There is prominent loss of motor neurons in the spinal cord and brainstem although the oculomotor neurons are spared. Large pyramidal motor neurons in layer V of motor cortex, which are the origin of the descending corticospinal tracts, are also lost. 

The neuraxis is the rostrocaudal extension of the nervous system including forebrain, midbrain, brainstem, spinal cord, and peripheral nerves. 

Major efferent projections of the hypothalamic orexin system comprise descending and ascending, dorsal and ventral pathways that terminate preferentially in aminergic, endocrine, and autonomic control centers in the hypothalamus, midbrain, brainstem, and spinal cord, as well as in limbic cortical and subcortical structures, including sqDtum, amygdala, thalamus,... 

Afferent input from cutaneous and visceral nociceptors is known to converge on spinal neurons, which accounts for the referral of pain between visceral and cutaneous structures (e.g. cardiac pain gets referred to the chest and left upper arm in patients suffering from angina pectoris). Projection neurons in the spinal dorsal horn project to cell nuclei in supraspinal areas such as the thalamus, brainstem and midbrain. Of these, the synaptic junctions in the thalamus play a very important role in the integration and modulation of spinal nociceptive and non-nociceptive inputs. Nociceptive inputs are finally conducted to the cortex where the sensation of pain is perceived (Fig. 1). The mechanisms via which the cortex processes nociceptive inputs are only poorly understood. 

The raphe nuclei are a cluster of nuclei found in the brainstem, where they are located in the medial portion of the formatio reticularis, the raphe. (The raphe is the junction of the left and right brainstem hemisphere, hence the name raphe=seam). Serotonergic nerve cells in the CNS originate from the raphe nuclei, i.e., their rostral portion, and because of their wide-ranging projections appear to supply serotonin (5HT) to the rest of the brain. 

Localization CNS Cortex, hippocampus, striatum, olfactory bulb, spinal cord CA/S not present in adult. CNS Choroid plexus, medulla, pons, striatum, hippocampus (CA1, CA3), hypothalamus, spinal cord CNS Striatum, hippocampus (CA1), substantia nigra, globus pal-lidus. CNS Striatum, brainstem, thalamus, hippocampus, olfactory bulb, substantia nigra... 

Saracibar G, Hernandez ML, Echevarria E, et al Toluene alters mu-opioid receptor expression in the rat brainstem. Ind Health 39 231-234, 2001 Schikler KN, Seitz K, Rice JF, et al Solvent abuse associated cortical atrophy. J Adolesc Health Care 3 37-39, 1982... 

The distribution of endosulfan and endosulfan sulfate was evaluated in the brains of cats given a single intravenous injection of 3 mg/kg endosulfan (Khanna et al. 1979). Peak concentrations of endosulfan in the brain were found at the earliest time point examined (15 minutes after administration) and then decreased. When tissue levels were expressed per gram of tissue, little differential was observed in distribution among the brain areas studied. However, if endosulfan levels were expressed per gram of tissue lipid, higher initial levels were observed in the cerebral cortex and cerebellum than in the spinal cord and brainstem. Loss of endosulfan was most rapid from those areas low in Upid. Endosulfan sulfate levels peaked in the brain at 1 hour postadministration. In contrast, endosulfan sulfate levels in liver peaked within 15 minutes postadministration. The time course of neurotoxic effects observed in the animals in this study corresponded most closely with endosulfan levels in the central nervous system tissues examined. 

The sensitivity and specificity of DWI depend to some extent on the technique being used and the amount of imaging time that can be dedicated to the DWI sequence. DWI pulse sequences typically require between approximately 30 seconds and 4 minutes of imaging time to image the entire brain and achieve sensitivity and specificity approaching 100% (Fig. 2.2). The rare infarcts that are not apparent on DWI are usually very small and are often located in the brainstem. 

FIGURE 4.2 (Continued) A compliant balloon was used to perform angioplasty (c). Postangioplasty angiogram demonstrated complete recanalization of the basilar artery and its major branches (d and e). MRI performed 2 days later demonstrated only small areas of infarction in the cerebellar hemispheres (arrows—f and g) but no brainstem or occipital infarcts. 

Stroke patients who require mechanical ventilation are not necessarily destined for a poor outcome. In a study by Santoli et al., 58 patients underwent mechanical ventilation and 16 survived. Eleven achieved a Barthel Index (BI) score of 60, indicating a good outcome. Within this study population, those patients with bilaterally absent comeal and pupillary reflexes had uniformly poor outcomes, underscoring the need for careful assessment of brainstem reflexes in intubated stroke patients. Other factors that have been associated with poor outcome in intubated stroke patients are advanced age and lower Glasgow Coma Score (GCS) at the time of intubation, as well as seizures and pulmonary edema. ... 

Figure 1.8 Some basic neuronal systems. The three different brain areas shown (I, II and III) are hypothetical but could correspond to cortex, brainstem and cord while the neurons and pathways are intended to represent broad generalisations rather than recognisable tracts. A represents large neurons which have long axons that pass directly from one brain region to another, as in the cortico spinal or cortico striatal tracts. Such axons have a restricted influence often only synapsing on one or a few distal neurons. B are smaller inter or intrinsic neurons that have their cell bodies, axons and terminals in the same brain area. They can occur in any region and control (depress or sensitise) adjacent neurons. C are neurons that cluster in specific nuclei and although their axons can form distinct pathways their influence is a modulating one, often on numerous neurons rather than directly controlling activity, as with A . Each type of neuron and system uses neurotransmitters with properties that facilitate their role...

Dahlstrom, A and Fuxe, K (1964) Evidence for the existence of monoamines containing neurons in the central nervous system. 1. Demonstration of monoamines in the cell bodies of brainstem neurons. Acta Physiol. Scand. 62 (Suppl 232) 1-55. 

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