Search

Background and Purpose: Abnormal cerebral microstructure has been documented in term neonates with congenital heart disease, portending risk for injury and poor neurodevelopmental outcome. Our hypothesis was that preterm neonates with congenital heart disease would demonstrate diffuse cerebral microstructural abnormalities when compared with critically ill neonates without congenital heart disease. A secondary aim was to identify any association between microstructural abnormalities, white matter injury (eg, punctate white matter lesions), and other clinical variables, including heart lesions., Materials and Methods: With the use of tract-based spatial statistics, an unbiased, voxelwise method for analyzing diffusion tensor imaging data, we compared 21 preterm neonates with congenital heart disease with 2 cohorts of neonates without congenital heart disease: 28 term and 27 preterm neonates, identified from the same neonatal intensive care unit., Results: Compared with term neonates without congenital heart disease, preterm neonates with congenital heart disease had microstructural abnormalities in widespread regions of the central white matter. However, 42% of the preterm neonates with congenital heart disease had punctate white matter lesions. When neonates with punctate white matter lesions were excluded, microstructural abnormalities remained only in the splenium. Preterm neonates with congenital heart disease had similar microstructure to preterm neonates without congenital heart disease., Conclusions: Diffuse microstructural abnormalities were observed in preterm neonates with congenital heart disease, strongly associated with punctate white matter lesions. Independently, regional vulnerability of the splenium, a structure associated with visual spatial function, was observed in all preterm neonates with congenital heart disease.

Antibodies directed against the Met-enkephalin-related hexapeptide, Met-enk Arg6, have been used in radioimmunoassays in the characterization of material in rat brain, and bovine striatum, colon, and adrenal medulla. Met-enk Lys6 reacted 0.27 relative to Met-enk Arg6, but Leu-enk Arg6 and C-terminal extensions or deletions of Met-enk Arg6 showed less than 0.02 immunoreactivity. In rat brain, the concentration of Met-enk Arg6-like immunoreactivity was less than 20 pmol X g-1 in all regions, but after trypsinization of tissue extracts there were up to 80-fold increases in immunoreactivity as a result of cleavage of C-terminally extended forms. The tryptic product eluted as Met-enk Arg6 on gel filtration. In control extracts of rat brain there were at least three immunoreactive forms of Met-enk Arg6; one eluted in the position of the hexapeptide standard on gel filtration and HPLC while the others had properties of N-terminally extended forms. In bovine striatum and colon the hexapeptide-like material predominated; but in bovine adrenal extracts, there were relatively low concentrations of the hexapeptide and, instead, the dominant immunoreactive forms corresponded to two components that were probably N-terminally extended variants. Trypsin again produced marked increases in immunoreactivity. HPLC studies indicated that Met-enk Arg6Phe7- and Met-enk Arg6Gly7Leu8-like immunoreactive peptides were important substrates in bovine brain for the production of hexapeptide immunoreactivity after trypsin. The differences in the patterns of immunoreactive forms in bovine adrenal, colon, and brain are consistent with tissue variations in the pathways of posttranslational processing of the precursor molecules.

The anatomical distribution of neuronal perikarya and nerve fibres containing FMRF-amide-like immunoreactivity in the brain, spinal cord and pituitary of the rat has been studied by immunohistochemistry. In animals pretreated with colchicine, the highest concentration of nerve cell bodies occurred in hypothalamic nuclei. Cells were also present in the cortex, striatum, septum, thalamus and in the brainstem. Beaded nerve fibres were abundant in the septum, nucleus of the striae terminalis, hypothalamus, medial regions of the thalamus, the parabrachial nucleus, the ventrolateral medulla, the substantia gelatinosa of the spinal trigeminal nucleus and the dorsal horn of the spinal cord. Fibres were also present in the cortex, striatum, amygdala, pons, ventral spinal cord and the neural lobe of the pituitary. The localization was specific in that preabsorbtion of the antisera with FMRF-amide, but not structurally related molecules such as Met-Enk-Arg6Phe7, APP or BPP, completely abolished the localization. The mammalian counterparts of FMRF-amide may have a neurotransmitter or neuromodulatory role.

The reliability of cranial computed tomography (CT) in detecting a broad range of intracerebral disorders has been well established (1) and its complementary role with other neuroradiologic procedures has been documented (2). Some attempts at inferring specific histologic diagnosis from static CT scans have been made (3,4). However, other investigators have demonstrated that it is difficult to separate cystic from noncystic, benign from malignant, and neoplastic from non-neoplastic lesions by absorption coefficients alone (5,6). While initial studies utilizing dynamic CT scanning indicate that patterns of contrast accumulation may be helpful in distinguishing enhancing cerebral lesions (7,16), the differential diagnosis of the low-attenuation lesion remains difficult (17). We present a series of hypodense lesions in the middle cranial fossa that demonstrate a broad range of pathologic entities. Their CT features, differential diagnosis, and pathologic correlation are discussed.

The postnatal development of cholecystokinin (CCK) in rat brain was studied by radioimmunoassay and bioassay of tissue extracts. Marked differences were found in the patterns of development in different regions of the brain. In the cerebellum and brainstem of newborn rats the concentrations of CCK8-like immunoreactivity were 40-100% those in adults, whereas in more rostral regions the concentrations were 1-10% of those in adults. Between 0 and 14 days in concentrations of CCK-like activity measured by radioimmunoassay increased up to 30-fold in hypothalamus, cortex and olfactory bulb; in the cortex there were further increases up to 42 days. Cortical CCK was also measured by bioassay on rabbit gall bladder in vitro; bioactivity was identified in foetuses, and after birth showed a similar pattern of increase to that measured by radioimmunoassay. Immunoreactive material in extracts of neonatal cerebellum, brainstem and cortex was identified as CCK8 on the basis of cross-reactivity with different antisera, and chromatographic properties on gel filtration. The results raise the possibility of different rates of maturation of central CCKergic systems.

The enkephalin-related heptapeptide, Tyr-Gly-Gly-Phe-Met-Arg-Phe, forms the C-terminus of a biosynthetic precursor that contains both Met-enkephalin and Leu-enkephalin sequences. We have studied the distribution of heptapeptide-like immunoreactivity in rat brain by immunohistochemistry using a C-terminal specific antiserum. The results were compared with those obtained using an antiserum specific for the C-terminus of Met-enkephalin which does not react with C-terminally-extended variants. Both antisera specifically stained cell bodies and fibres in many regions of the rat central nervous system. Colchicine was needed for the demonstration of cell bodies with the Met-enkephalin antiserum, but not for the heptapeptide antiserum. In the nucleus of the solitary tract, in the commissural nucleus, the nucleus raphe obscurus and in the hypothalamus, studies of serial sections and re-staining experiments indicated that the two antisera stained the same cell bodies. However, in the olfactory bulb, the anterior olfactory nucleus, the olfactory tubercle, the nucleus accumbens, caudate-putamen, central nucleus of the amygdala, nucleus interstitialis striae terminalis, pre-lateral mamillary nuclei, ventral hypothalamus, hippocampus, peri-aqueductal grey and the granular layer of the cerebellum, cells were stained by the heptapeptide antiserum but not the Met-enkephalin antiserum. The two antisera revealed similar patterns of staining of nerve fibres in many regions including hypothalamus, central nucleus of the amygdala, lateral septum, thalamus, mid-brain and spinal cord. But in other areas notably, pallidum, caudate-putamen, substantia inominata, nucleus of the solitary tract and commissural nucleus, there were abundant fibres and terminals revealed by the Met-enkephalin antiserum but not by the heptapeptide antiserum. The results are discussed with respect to possible patterns of enkephalin biosynthesis; it is suggested that in some neurones immunoreactive enkephalin precursors terminating in the heptapeptide sequence are processed to produce the heptapeptide which is stored in terminals and is available for release as an endogenous opioid agonist in its own right. In other cases, however, it is suggested that the heptapeptide might be cleaved by removal of -Arg-Phe to yield Met-enkephalin which is the primary opioid product of this class of neurone.

A wide variety of cystic appearing or low attenuation lesions in the midline posterior fossa can so closely resemble one another as to render specific histologic diagnosis from CT scans alone fraught with error. Absorption coefficients often overlap and are too nonspecific to infer consistently accurate histologic diagnosis. It is virtually impossible to separate cystic from noncystic, benign from malignant, and neoplastic from non-neoplastic lesions by absorption coefficients alone.