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Axonal elongation into peripheral nervous system "bridges" after central nervous system injury in adult rats.

The origin, termination, and length of axonal growth after focal central nervous system injury was examined in adult rats by means of a new experimental model. When peripheral nerve segments were used as "bridges" between the medulla and spinal cord, axons from neurons at both these levels grew approximately 30 millimeters. The regenerative potential of these central neurons seems to be expressed when the central nervous system glial environment is changed to that of the peripheral nervous system.

Animals↗

The immune system and the nervous system.

The immune system may interfere with brain function. The central nervous system may also influence the activity of the immune system. The central nervous system is functionally protected by the blood-brain barrier. The central nervous system is functionally protected by the blood-brain barrier. The endothelial cells of the brain capillaries are linked by tight junctions, resulting in an almost continuous interior wall which restricts the transfer of plasma proteins. The barrier function is modified by inflammatory meningeal lesions, stroke and epileptic seizures. Antigenic material may penetrate the barrier and enter the nerve tissue. The phagocytic cells in the central nervous system are mainly of haematogenous origin. The number of such cells in the brain is very low. There are also few lymphocytes under normal circumstances. These cells circulate from the blood, through the vessel walls and into the perivascular spaces, along the perivascular channels and to the CSF and back to the blood. This circulation may increase enormously during inflammatory conditions. In multiple sclerosis, the number of T-lymphocytes in the CSF is increased, corresponding to a preponderance of T-lymphocytes in the perivascular cell infiltrates in and around the lesions. Thus, the individual elements of the immune system are all present in the brain, which is only partially immunologically privileged. The mechanisms underlying the brain's immunological privilege may be of a non-immunological nature. As yet there are only few data which indicate that auto-immunity is a prominent feature in diseases of the human brain. The central nervous system also exerts a modulating influence upon the immune response. This may take place both by secretion of hormones and by a nervous/neurotransmitter influence upon the immune system.

Autoimmune Diseases↗

Immunoperoxidase labelled antibody staining in differential diagnosis of central nervous system haemangioblastomas and central nervous system metastases of renal carcinomas.

The problem of the differential diagnosis both of central nervous system haemangioblastomas and metastases of renal clear cell carcinomas was investigated by immunoperoxidase labelled antibody staining of five cases each of haemangioblastoma and metastatic renal carcinoma. Staining using anticarcinoembryonic antigen (CEA), antikeratin, antifactor VIII related antigen, and antibrush border was unhelpful. All five of the haemangioblastomas were negative and all five of the metastases were positive for epithelial membrane antigen (EMA), as defined by immunoperoxidase staining. This shows that commercially available anti-EMA monoclonal antibody is useful in distinguishing the two pathological entities.

Adenocarcinoma↗

[Interaction between the renin system and parasympathetic nervous system in heart failure].

UNLABELLED: The increase of sympathetic activity in heart failure is accompanied by a reduced parasympathetic tone. The renin-angiotensin system has not only multiple interactions with the sympathetic nervous system, but may also influence vagal tone directly by angiotensin II. Animal studies show a reduction of parasympathetic tone by a direct action of angiotensin II in the area postrema where the blood brain barrier is absent. It is possible that, in addition to the sympathetic and renin-angiotensin system, the parasympathetic nervous system may also influence prognosis in heart failure. Therefore, baroreflex sensitivity as (CBS) an index of vagal tone was examined in 35 patients with moderate to severe heart failure (NYHA II-III). Independent of the severity of heart failure BS was the lower the higher plasma-renin-activity was. Fifty-six months after the initial examination a comparison of the surviving patients (Group 1, n = 20) with the patients who died or underwent heart transplantation (Group 2, n = 15) did not reveal significant differences in the initial hemodynamic data. However, group 2 patients showed a tendency to higher initial plasma-renin-activity and significantly lower BS 1.3 +/- 0.2 vs. 2.2 +/- 0.3 ms/mm Hg; p < 0.05). CONCLUSION: In patients with heart failure a relation between the renin-angiotensin system and the parasympathetic nervous system is likely as there is a significant negative relationship between BS and plasma-renin-activity. Among patients with a similar degree of heart failure a low vagal tone identifies patients with a poor prognosis.

Adult↗

Planarian homologs of netrin and netrin receptor are required for proper regeneration of the central nervous system and the maintenance of nervous system architecture.

Conserved axon guidance mechanisms are essential for proper wiring of the nervous system during embryogenesis; however, the functions of these cues in adults and during regeneration remain poorly understood. Because freshwater planarians can regenerate a functional central nervous system (CNS) from almost any portion of their body, they are useful models in which to study the roles of guidance cues during neural regeneration. Here, we characterize two netrin homologs and one netrin receptor family member from Schmidtea mediterranea. RNAi analyses indicate that Smed-netR (netrin receptor) and Smed-netrin2 are required for proper CNS regeneration and that Smed-netR may mediate the response to Smed-netrin2. Remarkably, Smed-netR and Smed-netrin2 are also required in intact planarians to maintain the proper patterning of the CNS. These results suggest a crucial role for guidance cues, not only in CNS regeneration but also in maintenance of neural architecture.

Animals↗

Central nervous system origins of the sympathetic nervous system outflow to white adipose tissue.

White adipose tissue (WAT) is innervated by postganglionic sympathetic nervous system (SNS) neurons, suggesting that lipid mobilization could be regulated by the SNS [T. G. Youngstrom and T. J. Bartness. Am. J. Physiol. 268 (Regulatory Integrative Comp. Physiol. 37): R744-R751, 1995]. A viral transsynaptic retrograde tract tracer, the pseudorabies virus (PRV), was used to identify the origins of the SNS outflow from the brain to WAT neuroanatomically. PRV was injected into epididymal or inguinal WAT (EWAT and IWAT, respectively) of Siberian hamsters and IWAT of rats. PRV-infected neurons were visualized by immunocytochemistry and found in the spinal cord, brain stem (medulla, nucleus of the solitary tract, caudal raphe nucleus, C1 and A5 regions), midbrain (central gray), and several areas within the forebrain. The general pattern of infection of WAT in both species was more similar than different and resembled that seen after PRV injections into the adrenal medulla in rats (A. M. Strack, W. B. Sawyer, J. H. Hughes, K. B. Platt, and A. D. Loewy. Brain Res. 491: 156-162, 1989). EWAT versus IWAT injected hamsters had relatively less labeling in the suprachiasmatic, dorsomedial, and arcuate nuclei. Overall, it appeared that the SNS innervation of WAT originates from the general SNS outflow of the central nervous system and therefore may play a significant role in lipid mobilization.

Adipose Tissue↗

Distinguishing primary central nervous system lymphoma from other central nervous system diseases: a neurosurgical perspective on diagnostic dilemmas and approaches.

OBJECT: White matter diseases, including demyelinating or inflammatory disorders, may be indistinguishable clinically and radiologically from some central nervous system (CNS) tumors. In such situations, determination of the final diagnosis is difficult. An example is the differential diagnosis of non-acquired immunodeficiency syndrome-related primary central nervous system lymphoma (PCNSL) and multiple sclerosis (MS), a demyelinating disease. Unfortunately, delayed diagnosis and treatment of PCNSL can negatively affect prognosis. METHODS: The authors reviewed the cases of eight patients with PCNSL or MS. In each case, the initial diagnosis (PCNSL or MS) was equivocal. In these cases, conventional diagnostic approaches were not definitive, thus further delaying diagnosis. The initial symptoms, the selected diagnostic tests, and the presumptive as well as final diagnosis for each case are discussed. The final diagnosis was PCNSL in six cases and MS in two. The uncertainty about the clinical or initial pathological presentation required further diagnostic evaluation in all cases. Two important neurosurgical guidelines are the avoidance of corticosteroid agents and performance of biopsy sampling rather than volumetric tumor resection. Highvolume lumbar puncture, slit-lamp examination/vitrectomy, new CNS imaging techniques, and repeated biopsy procedures also proved helpful. CONCLUSIONS: In PCNSL, early definitive diagnosis and treatment are the keys to successful outcomes. Knowledge of strategies essential to early diagnosis lessens the need for brain biopsy sampling, but this procedure is still usually necessary. In such selected cases, biopsy sampling is appropriate even when pathological investigation shows MS rather than PCNSL. Complete resection is not indicated in PCNSL and can lead to additional sequelae.

Adolescent↗

Role of the parasympathetic nervous system and interaction with the sympathetic nervous system in the early phase of hypertension.

The role of the peripheral parasympathetic nervous system in the development of hypertension was investigated in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Animals were 5-7 weeks old, anesthetized, and in the open-chest condition. The decrement in heart rate evoked by parasympathetic nerve stimulation (62 +/- 8 beats/min) in SHR was greater (p < 0.01) than that in WKY rats (23 +/- 4 beats/min). Furthermore, the decrease in heart rate (73 +/- 9 beats/min) in response to combined stimulation of sympathetic and parasympathetic nerves in SHR was greater (p < 0.05) than that in response to vagal stimulation alone. The extent of the interaction of sympathetic and parasympathetic nerves was calculated as the difference between the decrease in heart rate during combined stimulation and that during vagal nerve stimulation alone. The extent of the interaction in SHR (-11 +/- 5) was not significantly different from that in WKY rats (-8 +/- 3 beats/min). Therefore, the influence of the peripheral parasympathetic nervous system in the early phase of hypertension may be greater than that in the normotensive state. Interaction between the two branches of the autonomic nervous system may occur as accentuated antagonism originating in the early phase of hypertension. The interaction during the early phase of hypertension may not be different in extent from that of the normotensive state.

Animals↗

New approaches to the study of central nervous system function. Immune-nervous system interactions and cell culture.

The paper by Lal and Forster is discussed with reference to future experiments which might provide insight into mechanisms regarding their exciting data that circulating brain reactive antibodies may cause learning deficits. The paper by Azmitia et al. on cell culture techniques is discussed with respect to the types of studies in which culture systems have proven most valuable in the past, and should continue to do so in the future.

Aging↗

Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 4. Central nervous system depressants.

The synthesis of 1'-[3-(4-fluorobenzyoyl)propyl]-3-phenylspiro[isobenzofuran-1(3H),4'-piperidine] (2a) and eight halo and methoxy analogues is described. The compounds were generally more potent per os than chlorpromazine in the Sidman avoidance paradigm in rats and less potent than haloperido. 1'-[3-(4-Fluorobenzoyl)propyl]-3-(4-fluorophenyl)spiro[isobenzofuran-1(3H),4'-piperidine] (2e) approached the per os potency of haloperidol in this test and was shown to be active in inhibiting monkey avoidance also. Compound 2e was much less active than haloperidol in antagonizing apomorphine-induced emesis in dogs, apomorphine-induced stereotypy in rats, and amphetamine-induced circling in lesioned rats. This lack of nonselective, dopamine-receptor blocking effects makes 2e attrative as a potential neuroleptic.

Amphetamine↗