Segregation of optic axons based on central target: the medial optic tract in Rana pipiens

The electrophysiological integrity of the adult rat spinal cord was assessed at the lumbar, lower cervical and cortical levels after the animals sustained a severe contusion injury at the mid-thoracic level (T8) and received either carbon filament cultured with fetal spinal cord tissue implants, fetal tissue implants, or carbon filament implants alone. Somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) were recorded from all animal groups at the end of the 8-week survival period. The results of this study demonstrate that the spinal cord injured animals that received carbon filament cultured with fetal spinal cord tissue implants had the highest degree of electrophysiological recovery, indicating that this combination plays an important role in promoting recovery after injury.     

Regeneration of retinal axons into the goldfish optic tectum

The growth of regenerating retinal axons into the central portion of the optic tectum of adult goldfish was examined with the light and electron microscopes. Optic tracts were cut and, two days to five months later, the animals were perfused and the tecta prepared for microscopy. Regenerating axons first reached central regions of the tectum seven to ten days postoperatively. Regenerating axons appear in very large numbers and travel in fascicles in the stratum opticum (SO) and in the adjacent neuropil, the stratum fibrosum et griseum superficiale (SFGS). In the SO, the fascicles are bordered by glial cells and degenerating debris. Within the SFGS, however, the fascicles do not seem to be similarly associated with glial cells and degenerating debris. The youngest regenerating axons are very slender processes, containing microtubules but few or no neurofilaments or dense granular material. By 10 to 14 days postoperatively, neurofilaments can be seen and, in addition, large numbers of vesicles with dense cores appear. The vesicles with dense cores increase in numbers until about 28 days postoperatively and then become quite rare. That vesicles with dense cores were seen in regenerating axons in both SO and SFGS during the period of growth into the tectum but were not seen in axon terminals at any time, suggests that they may be concerned with axon elongation. During the period one month to five months postoperatively, the regenerating axons gradually increase in diameter but do not reach preoperative sizes, suggesting that the regenerative changes may still be occurring. Remyelination is delayed and proceeds slowly. Many axons remain unmyelinated for as long as five months postoperatively.     

Sound and vibration sensitivity of VIIIth nerve fibers in the frogs Leptodactylus albilabris and Rana pipiens pipiens

1. Responses of 73 fibers to dorso-ventral vibration were recorded in the saccular and utricular branchlets of Rana pipiens pipiens using a ventral approach. The saccular branchlet contained nearly exclusively vibration-sensitive fibers (33 out of 36) with best frequencies (BFs) between 10 and 70 Hz, whereas none of the 37 fibers encountered in the utricular branchlet responded to dorso-ventral vibrations. 2. Using a dorsal approach we recorded from the VIIIth nerve near its entry in the brainstem and analyzed responses to both sound and vibration stimuli for 65 fibers in R. pipiens pipiens and 25 fibers in Leptodactylus albilabris. The fibers were classified as amphibian papilla (AP), basilar papilla (BP), saccular or vestibular fibers based on their location in the nerve. Only AP and saccular fibers responded to vibrations. The AP-fibers responded to vibrations from 0.01 cm/s2 and to sound from 40 dB SPL by increasing their spike rate. Best frequencies (BFs) ranged from 60 to 900 Hz, and only fibers with BFs below 500 Hz responded to vibrations. The fibers had identical BF's for sound and vibration. The saccular fibers had BFs ranging from 10 to 80 Hz with 22 fibers having BFs at 40-50 Hz. The fibers responded to sound from 70 dB SPL and to vibrations from 0.01 cm/s2. 3. No differences in sensitivity, tuning or phase-locking were found between the two species, except that most BP-fibers in R. pipiens pipiens had BFs from 1.2 to 1.4 kHz, whereas those in L. albilabris had BFs from 2.0 to 2.2 kHz (matching the energy peak of L. albilabris' mating call). 4. The finding that the low-frequency amphibian papilla fibers are extremely sensitive to vibrations raises questions regarding their function in the behaving animal. They may be substrate vibration receptors, respond to sound-induced vibrations or bone-conducted sound.     

Topographical distribution of NADPH-diaphorase activity in the central nervous system of the frog, Rana perezi

The distribution of NADPH-diaphorase (ND) activity was histochemically investigated in the brain of the frog Rana perezi. This technique provides a highly selective labeling of neurons and tracts. In the telencephalon, labeled cells are present in the olfactory bulb, pallial regions, septal area, nucleus of the diagonal band, striatum, and amygdala. Positive neurons surround the preoptic and infundibular recesses of the third ventricle. The magnocellular and suprachiasmatic hypothalamic nuclei contain stained cells. Numerous neurons are present in the anterior, lateral anterior, central, and lateral posteroventral thalamic nuclei. Positive terminal fields are organized in the same thalamic areas but most conspicuously in the visual recipient plexus of Bellonci, corpus geniculatum of the thalamus, and the superficial ventral thalamic nucleus. Labeled fibers and cell groups are observed in the pretectal area, the mesencephalic optic tectum, and the torus semicircularis. The nuclei of the mesencephalic tegmentum contain abundant labeled cells and a conspicuous cell population is localized medial and caudal to the isthmic nucleus. Numerous cells in the rhombencephalon are distributed in the octaval area, raphe nucleus, reticular nuclei, sensory trigeminal nuclei, nucleus of the solitary tract, and, at the obex levels, the dorsal column nucleus. Positive fibers are abundant in the superior olivary nucleus, the descending trigeminal, and the solitary tracts. In the spinal cord, a large population of intensely labeled neurons is present in all fields of the gray matter throughout its rostrocaudal extent. Several sensory pathways were heavily stained including part of the olfactory, visual, auditory, and somatosensory pathways. The distribution of ND-positive cells did not correspond to any single known neurotransmitter or neuroactive molecule system. In particular, abundant codistribution of ND and catecholamines is found in the anuran brain. Double labeling techniques have revealed restricted colocalization in the same neurons and only in the posterior tubercle and locus coeruleus. If ND is in amphibians a selective marker for neurons containing nitric oxide synthase, as generally proposed, with this method the neurons that may synthesize nitric oxide would be identified. This study provides evidence that nitric oxide may be involved in novel tasks, primarily related to forebrain functions, that are already present in amphibians.     

Regeneration of adult axons in white matter tracts of the central nervous system

It is widely accepted that the adult mammalian central nervous system (CNS) is unable to regenerate axons. In addition to physical or molecular barriers presented by glial scarring at the lesion site, it has been suggested that the normal myelinated CNS environment contains potent growth inhibitors or lacks growth-promoting molecules. Here we investigate whether adult CNS white matter can support long-distance regeneration of adult axons in the absence of glial scarring, by using a microtransplantation technique that minimizes scarring to inject minute volumes of dissociated adult rat dorsal root ganglia directly into adult rat CNS pathways. This atraumatic injection procedure allowed considerable numbers of regenerating adult axons immediate access to the host glial terrain, where we found that they rapidly extended for long distances in white matter, eventually invading grey matter. Abortive regeneration correlated precisely with increased levels of proteoglycans within the extracellular matrix at the transplant interface, whereas successfully regenerating transplants were associated with minimal upregulation of these molecules. Our results demonstrate, to our knowledge for the first time, that reactive glial extracellular matrix at the lesion site is directly associated with failure of axon regrowth in vivo, and that adult myelinated white matter tracts beyond the glial scar can be highly permissive for regeneration.     

Developmental failures of blood vessels within central nervous system

Improved prevention and detection methods, as well as advances in medical treatment have resulted in a trend of increasing numbers of cancer survivors. Today, there are over 8 million cancer survivors, 5 million of whom were diagnosed 5 or more years ago. Cancer, once thought of as an acute disease, is increasingly being classified as a chronic disease. This article reviews physical, psychological, and social aspects of cancer survivorship, as well as other issues related to a diagnosis of cancer.     

Ischemic injury of optic nerve axons: the nuts and bolts

The disposition of enrofloxacin was measured after intravenous and oral administration to pigs. Eight clinically healthy pigs weighing 25 to 40 kg received a dose of 5 mg/kg intravenously and 10 mg/kg orally in both a fasted and a fed condition in a three-way cross-over design. Enrofloxacin was present in plasma for up to 72 hr after both intravenous and oral administration to fasted as well as fed pigs. The steady state volume of distribution was determined to 3.9 +/- 0.5 1/kg body weight which indicates that enrofloxacin was widely distributed in the body. The bioavailability was determined to 83 +/- 13% in fed and to 101 +/- 32% in fasted pigs. Based on the bioavailability and the resulting plasma concentrations it is concluded that a therapeutically active concentration for the most common porcine microbial pathogens are maintained for at least 24 hr after oral administration of 10 mg/kg body weight to fasted as well as to fed pigs. Ciprofloxacin which is an active metabolite of enrofloxacin was observed in plasma samples from all treated pigs, but the concentration never exceeded 0.1 microgram/ml. During the first 24 hr after the administration of enrofloxacin the concentration of the metabolite made up less than 10% of the corresponding concentration of the parent compound.     

Different types of centrally acting antihypertensives and their targets in the central nervous system

The central regulation of blood pressure and other cardiovascular parameters may involve the baroreceptor reflex are, including both adrenergic and serotonergic pathways, as well as amino acids, as neurotransmitters. Both adrenergic and serotonergic pathways have been recognized as targets for clinically relevant, centrally acting antihypertensives, such as clonidine, guanfacine, and alpha-methyl-DOPA. The central components of the hybrid drugs urapidil and ketanserin also involve serotonergic pathways and receptors. For urapidil the stimulation of 5-HT1A-receptors is assumed to induce peripheral sympathoinhibition, whereas for ketanserin the central mechanism is unknown in detail. More recently central imidazoline (I1) receptors have been proposed as the major target for the newer antihypertensives rilmenidine and moxonidine. Clonidine, however, is assumed to be mixed I1- and alpha2-receptor agonist. The distinction between central I1- and alpha2-receptors may potentially offer the design of new antihypertensives, acting like clonidine but with fewer side effects. Finally, the amino acid pathways should be considered as potential targets for centrally acting antihypertensives. Experimental compounds on this basis are available but clinical implications appear to be very remote. In the present survey an outline is given of the various pathways, neurotransmitters, and receptors involved in the central regulation of blood pressure. The different types of centrally acting antihypertensives are subsequently discussed on this basis.     

Regulation of retinal and optic nerve blood flow

Blood flow to the retina and optic nerve remains constant over a range of elevated intraocular pressure or mean arterial pressure, independent of sympathetic activation (pressure autoregulation). In addition, increased metabolic activity in these tissues proportionally increases blood flow (metabolic autoregulation). At constant metabolic rate, altered arterial oxygen content reciprocally alters blood flow, leaving total oxygen delivery constant, while blood flow rises and falls with the arterial carbon dioxide tension. These responses are similar to those of the cerebral circulation. However, while aging, atherosclerosis, arterial hypotension, and individual variation may profoundly alter blood flow regulation and predispose to the development of illness, these factors remain largely unexplored.     

Temporal changes in beta-tubulin and neurofilament mRNA levels after transection of adult rat retinal ganglion cell axons in the optic nerve

Axons of adult mammalian retinal ganglion cells (RGCs) do not regenerate spontaneously after injury in the optic nerve and show a persistent decrease in the rate of transport of tubulin and neurofilament proteins. To investigate further the expression of cytoskeletal proteins in these axotomized CNS neurons, mRNA levels of beta-tubulin and the 150 kDa neurofilament subunit (NF-M) were measured after interrupting the optic nerve 9 mm from the eye. Northern blots of RNA extracted from whole retinas after optic nerve transection showed that the total level of both of these mRNAs fell after injury. To determine if this decrease was a result of the death of axotomized RGCs or reflected changes in individual neurons, RNA probes were hybridized to radial cryostat sections of normal and axotomized retinas from 1 d to 6 months after injury. Grain counts revealed two trends of tubulin expression in RGCs. An early increase in tubulin mRNAs in the axotomized RGCs was followed by a later decrease. Such an increase in tubulin mRNA levels has been correlated with regenerative growth in other neurons. By 1 week after injury, the beta-tubulin mRNA levels decreased to 70% of the control value. Moreover, the time of this fall coincided with the onset of a marked slowing of cytoskeletal transport that follows injury in the optic nerve. In contrast, NF-M mRNA levels dropped immediately after axotomy, and remained at 80% of the control level. It is suggested that the transient increase in tubulin mRNAs may reflect an early regenerative response whose persistence depends on further growth cone interactions with the substrate.     

Urotensin II in the central nervous system of the frog Rana ridibunda: immunohistochemical localization and biochemical characterization

Urotensin II (UII) is traditionally regarded as a product of the neurosecretory cells in the caudal portion of the spinal cord of jawed fishes. A peptide related to UII has been recently isolated from the frog brain, thereby providing the first evidence that UII is also present in the central nervous system of a tetrapod. In the present study, we have investigated the distribution of UII-immunoreactive elements in the brain and spinal cord of the frog Rana ridibunda by immunofluorescence using an antiserum directed against the conserved cyclic region of the peptide. Two distinct populations of UII-immunoreactive perikarya were visualized. The first group of positive neurons was found in the nucleus hypoglossus of the medulla oblongata, which controls two striated muscles of the tongue. The second population of immunoreactive cell bodies was represented by a subset of motoneurons that were particularly abundant in the caudal region of the cord (34% of the motoneuron population). The telencephalon, diencephalon, mesencephalon, and metencephalon were totally devoid of UII-containing cell bodies but displayed dense networks of UII-immunoreactive fibers, notably in the thalamus, the tectum, the tegmentum, and the granular layer of the cerebellum. In addition, a dense bundle of long varicose processes projecting rostrocaudally was observed coursing along the ventral surface of the brain from the midtelencephalon to the medulla oblongata. Reversed-phase high-performance liquid chromatography analysis of frog brain, medulla oblongata, and spinal cord extracts revealed that, in all three regions, UII-immunoreactive material eluted as a single peak which exhibited the same retention time as synthetic frog UII. Taken together, these data indicate that UII, in addition to its neuroendocrine functions in fish, is a potential regulatory peptide in the central nervous system of amphibians.     

Aging and the central nervous system

This review of the literature on aging and the central nervous system attempts to cover the basic perameters investigated at both human and infrahuman levels for the better part of the last century. The results have indicated that there is a rather considerable lack of consistency in the data both within the frame of reference of a single species, and with regard to intraspecies comparisons. We have suggested that possible reasons for the contradictory findings would rest upon variability in techniques employed but, perhaps more importantly, on the failure of investigators in this area to standardize terminology. It is suggested that such a standardization might well be one of the more useful things to be accomplished in order to facilitate the interpretation of future work. The literature review first dealt with gross, i.e., macroscopic changes in brain morphology that could correlate with age, and then covered changes at the microscopic level. Finally, a brief review of the literature with regard to the biochemistry of aging was carried out. Implications of the data were noted where appropriate.     

Cyclooxygenases and the central nervous system

Prostaglandins (PGs) were first described in the brain by Samuelsson over 30 years ago (Samuelsson, 1964). Since then a large number of studies have shown that PGs are formed in regions of the brain and spinal cord in response to a variety of stimuli. The recent identification of two forms of cyclooxygenase (COX; Kujubu et al., 1991; Xie et al., 1991; Smith and DeWitt, 1996), both of which are expressed in the brain, along with superior tools for mapping COX distribution, has spurred a resurgence of interest in the role of PGs in the central nervous system (CNS). In this review we will describe new data in this area, focusing on the distribution and potential role of the COX isoforms in brain function and disease.     

Remyelination of the central nervous system

The three typical stages in the clinical course of multiple sclerosis (relapse, persistent disability and progression) can be explained on the basis of inflammation, demyelination and failure of repair leading to axon degeneration and astrocytosis. Strategies are being evaluated for limiting the inflammatory process using immunological treatments and these may have unexpected dividends in promoting endogenous remyelination. Increasing knowledge on glial lineages and axon-glial interactions needed for stable myelination also offer the prospect for enhancing remyelination through growth factor therapy and cell implantation.     

Tumors of the central nervous system

Neoplasia of the central nervous system (CNS) can be divided into two main categories: nonpituitary CNS neoplasia and pituitary adenomas. Nonpituitary CNS neoplasias are generally compressive in nature, although some are also invasive. The majority of reported CNS tumors are secondary with only a few originating from nervous tissue. Pituitary adenomas predominantly occur in the pars intermedia of the older horse. Clinical signs, diagnostic testing, and possible treatments are discussed.     

Cardiopulmonary bypass, rewarming, and central nervous system dysfunction

BACKGROUND: During cardiopulmonary bypass a nasopharyngeal temperature greater than 38 degrees C at the end of rewarming may indicate cerebral hyperthermia. This could exacerbate an ischemic brain injury incurred during cardiopulmonary bypass. METHODS: In a cohort of 150 aortocoronary bypass patients neuropsychologic test scores of 66 patients whose rewarming temperature exceeded 38 degrees C were compared with those who did not. There were no differences between groups with respect to demographic and intraoperative variables. RESULTS: A trend was seen for hyperthermic patients to do worse on all neuropsychologic tests in the early postoperative period but not at 3-month follow-up. By analysis of covariance hyperthermic patients did worse on the visual reproduction subtest of the Weschler memory scale at 3 months (p = 0.02), but this difference was not found by linear regression (p = 0.10). CONCLUSIONS: We were unable to demonstrate any significant deterioration in patients rewarmed to greater than 38 degrees C in the early postoperative period. The poorer performance in the visual reproduction subtest of the Wechsler memory scale at 3 months in the group rewarmed to more than 38 degrees C is interesting but far from conclusive. Caution with rewarming is still advised pending more in-depth study of this issue.