Rat models of middle cerebral artery ischemia.
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Biomedical subjects
Publications and source records attributed to W A Taylor.
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This chapter addresses the acute treatment of alcohol and cocaine. Because of the widespread use of both these drugs, health professionals must recognize the medical complications of alcohol and cocaine abuse and addiction. The biochemistry will be briefly reviewed as an avenue to understand the different treatment targets and modalities.
The management of hydrocephalus secondary to a posterior fossa tumour is controversial. We audited recent practice with a retrospective analysis of 287 consecutive patients undergoing posterior fossa exploration for tumour. 85 shunts and 112 external ventricular drains (EVD) were placed. The overall CNS infection rate in the series was 6%. There was a significantly higher (p less than 0.01) infection rate in patients who had a drainage procedure, and a trend towards higher infection rates in patients with two drainage procedures. Early infection rates with EVDs and shunts were the same (7%). One third of patients with hydrocephalus had pre-operative drainage, a third had per-operative drainage but only a quarter required a permanent shunt. The majority of patients will not require a permanent shunt and where temporary CSF diversion is required EVD is reasonable.
Thymidine incorporation proliferation assays to whole bovine P2 protein and its 58-81 and 14-25 synthetic peptides were performed on blood mononuclear cells from ten patients with Guillain-Barré syndrome (GBS), six patients with chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), and age and sex matched normal subjects. The only patients whose cells showed any response were two out of four with very early GBS. One responded to P2 and both synthetic peptides. One responded to P2 but to neither peptide. The results support a role for cell mediated immunity to P2 protein in some patients with Guillain-Barré syndrome.
Guillain-Barré syndrome (GBS), chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), and multiple sclerosis (MS) are disorders with presumed immunopathogenesis. To obtain evidence for T cell activation, we determined serum concentrations of soluble interleukin-2 receptors (sIL-2 R) in 50 patients with GBS, 24 with CIDP, and 54 with MS. Both in GBS and clinically active MS sIL-2 R levels were markedly increased compared with those in patients with other neurologic diseases. Four of 24 CIDP patients had abnormally increased sIL-2 R concentrations. sIL-2 R concentrations decreased with clinical improvement in serial samples taken from GBS patients, but were not otherwise correlated with disease severity. These data establish that T cells are activated in GBS and some patients with CIDP, and corroborate earlier evidence that activated T cells are circulating in the blood of MS patients.
When pharmacologic agents are considered in the treatment of cocaine addiction, the objective of such treatment--sustained abstinence--must be considered. Medication and medical approaches have been disappointing in the treatment of cocaine overdose. The central neurobiologic mechanism(s) involved in cocaine toxicity are poorly understood. Without a cocaine antagonist, pharmacologic approaches have been less than promising in preventing relapse. Various psychoactive medications have been tried in early cocaine abstinence, with some success.
In a Latin-square double-crossover with random assignment to sequence, 18 boys, aged 6-12 years, with attention-deficit hyperactivity disorder received 1 month each of placebo, D-amphetamine, and Efamol (evening primrose oil containing gamma-linolenic acid, with vitamin E as preservative). Parents' ratings were noncontributory. Teachers' ratings showed a trend of Efamol effect between placebo and D-amphetamine. The trend reached significance (p less than 0.05) only on Conners Hyperactivity Factor. Dosage may be crucial; 8 Efamol capsules per day were used in this study. Heuristic data scrutiny suggested possible interaction (sequence effect). Further study with a different design and dose is suggested. This study does not establish Efamol as an effective treatment.
High dose methylprednisolone (50 mg kg-1, daily) was administered to Lewis rats with experimental allergic neuritis from onset of the disease. Disease severity was reduced and recovery was significantly more rapid than that in saline-injected controls. Histological examination showed reduction of endoneurial edema, cellular infiltration, and demyelination. The results provide experimental evidence supporting the trial of high dose steroids in human demyelinating polyradiculoneuropathy.
Activated circulating T lymphocytes were measured in ten patients with Guillain-Barré syndrome (GBS) and in ten with chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), each paired with an age- and sex-matched healthy control. Activated T cells were identified by double labelling with phycoerythrin-conjugated anti-CD3 antibody and biotinylated antibodies to activation antigens: human leucocyte antigen (HLA)-DR, transferrin receptor (TFR) or interleukin-2 receptor (IL-2R) visualised with an avidin-biotin-fluorescein system. The frequency of activated T cells was increased in the GBS group. The median of the DR-positive T cells in the patients was 3.4% (range 0.5-9.4%), compared with 1.4% (range 0-4.3%) in the controls (P less than 0.01). For TFR the corresponding medians were 3.3% (range 0.5-6.2%) in the patients and 0% (range 0-2.5%) in the controls (P less than 0.01), and for IL-2R 3.7% (range 0-6.0%) in the patients compared with 0% (range 0-2.9%) in the controls (P less than 0.01). In the CIDP group the median percentage of activated T cells was also increased but the differences were less significant: for DR, patients 2.4% (range 0-3.8%), controls 0.5% (range 0-2.0%, P less than 0.05); for TFR, patients 0% (range 0-5.3%), controls 0% (range 0-1.0%, not significant), and for IL-2R, patients 0% (range 0-2.5%), controls 0% (range 0-0.5%, not significant). The activated cells might be directed against microbial antigens encountered during the infection preceding GBS, autoantigens, bacterial antigens encountered during concurrent infection, or a combination of these.
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Products of the bacterium Pseudomonas aeruginosa have been shown to slow the beating of human respiratory tract cilia in vitro. We have tested the effects of two of these compounds, pyocyanin and 1-hydroxyphenazine (given as a bolus dose dissolved in 2 microliters Ringer solution), on tracheal mucus velocity of radiolabeled erythrocytes in anesthetized guinea pigs. 1-Hydroxyphenazine (200 ng) caused a rapid slowing of tracheal mucus velocity (maximum fall 47% at 20 min) with recovery by 1 h. The effect of pyocyanin was slower in onset, 600 ng causing 60% reduction in tracheal mucus velocity at 3 h, and no recovery occurred. A combination of pyocyanin and 1-hydroxyphenazine produced an initial rapid slowing equivalent to the same dose of 1-hydroxyphenazine given alone, but the later slowing attributed to pyocyanin was greater than the same dose administered alone. This study demonstrates one mechanism by which products of P. aeruginosa may facilitate its colonization of the respiratory tract.
Experimental allergic neuritis (EAN) was induced in Lewis rats by immunisation with bovine spinal root myelin. Neurological signs appeared on day 12 and persisted for 10-15 days. A transient protein P2-specific proliferative response of circulating mononuclear cells was detected on days 10 and 14 after immunisation but not on days 17 and 35. Mononuclear cells recovered from cauda equina infiltrates on days 14 and 17 showed greater responsiveness to P2 than circulating cells. A P2-specific, interleukin-2-dependent T cell line has been developed from cauda equina (CE)-derived lymphocytes. In adoptive transfer experiments this cell line did not induce EAN but did protect normal recipients from actively induced EAN.
Lewis rats were maintained on a diet enriched with menhaden oil, a rich source of the arachidonic acid (AA) substitute eicosapentaenoic acid (EPA). After dietary manipulation the blood neutrophils showed normal leukotriene (LT)B4 but increased LTB5 concentrations, and the CD4+/CD8+T lymphocyte subset ratio was temporarily perturbed. The dietary manipulation did not affect the severity of actively induced experimental allergic neuritis (EAN).
The immune responses of 100 patients who presented with an acute idiopathic neuropathy were compared with those of age and sex matched controls. Blood lymphocytes and their subsets were counted with a fluorescent activated cell sorter. CD8+ (putative suppressor) lymphocytes were significantly reduced in the first week of the disease but total lymphocytes, total T and CD4+ (putative helper) cells were not altered. This reduction depended on the nature of the preceding infection. Serum complement C3 and C4 concentrations remained normal and immune complexes were rarely detected with a C1q binding assay. Complement-fixing antibodies to human peripheral nerve antigens were discovered in the serum of 7% of patients but only 1% of controls. Complement-fixing antibodies to galactocerebroside were not discovered in any sera. Enzyme-linked immunoassays detected increased antibody responses to galactocerebroside but none at all to human P2 myelin protein in the patient sera. Forty microliter of serum from five patients injected into the sciatic nerves of rats did not induce significantly more demyelination than the serum from control patients. It is concluded that auto-immune responses can only be detected by these techniques in a small minority of patients with acute idiopathic neuropathy.
Major histocompatibility antigens were identified in frozen sections of normal Lewis rat peripheral nerve tissue with monoclonal antibodies and an avidin-biotin-peroxidase complex system. Class I antigen is normally required for cytotoxic/suppressor T lymphocyte function and class II antigen for activation of helper T lymphocytes. In the sciatic nerves class I antigen was expressed diffusely by most endoneurial and perineurial cells but class II antigen only by a minority. In the cauda equina class I antigen was expressed by all arachnoid and some endoneurial cells, while class II antigen was expressed by a smaller proportion of arachnoid cells in the endoneurium of spinal roots and interstitial cells surrounding dorsal root ganglion neurons. The endothelium of endoneurial, perineurial and meningeal vessels uniformly expressed class I but not class II antigen. Experimental allergic neuritis was induced in Lewis rats by immunisation with bovine intradural root myelin. Early lesions consisted of multifocal infiltration of the nerve roots by cells expressing leucocyte common antigen. Surrounding endoneurial cells showed markedly increased expression of major histocompatibility antigens. In inflammatory lesions about 10% of the cells were stained with pan T cell antibodies. T lymphocyte subsets were identified with antibody W3/25 for helper cells and MRC OX-8 for cytotoxic/suppressor cells. The W3/25 positive cells were usually slightly in excess of OX-8 positive cells and their relative proportions did not alter during the disease. The presence of class I antigen on normal endothelium and its increased expression on endoneurial cells in the early phase of inflammation suggest an important role for class I restricted lymphocytes in the pathogenesis of the early stages of experimental allergic neuritis.
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P0 protein was prepared from bovine spinal root myelin. The purity was shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunostaining with affinity purified antisera. P0 in the presence of lysophosphatidylcholine induced paralysis and histological lesions resembling experimental allergic neuritis in Lewis rats. Lysophosphatidylcholine also enhanced the ability of P2 to produce neuritis. The conformation of these proteins may be important in determining their ability to induce experimental allergic neuritis. P0 deserves consideration as an antigen relevant to Guillain-Barré syndrome.
1. Genetically obese Zucker rats (fa/fa) contain 2-3 times higher activities mono- and diacylglycerol lipases in their spinal cords than their lean littermates. 2. When rats were exercised (1 hr daily, 5 days/week) on a treadmill for 6 months, there was a decrease of about 30% (P less than 0.05) in the activities of mono- and diacylglycerol lipases in lean rats but not in obese animals. 3. High activities of lipases in Zucker obese rats may be related to the elevated levels of beta-endorphin present in these animals. 4. The activities of arylsulfatase, beta-N-acetylhexosaminidase and alkaline phosphatase, tested to check the stability of spinal cord extracts, were similar in lean and obese rat spinal cords.