Neurofilament light chain levels in ventricular cerebrospinal fluid after acute aneurysmal subarachnoid haemorrhage.

PURPOSE: The contribution of axonal injury to brain damage after aneurysmal subarachnoid haemorrhage (aSAH) is unknown. Neurofilament light chain (NF-L), a component of the axonal cytoskeleton, has been shown to be elevated in the cerebrospinal fluid of patients with many types of axonal injury. We hypothesised that patients with aSAH would have elevated cerebrospinal fluid (CSF) NF-L levels and sought to explore the clinical correlates of CSF NF-L dynamics. METHODS: Serial ventricular CSF (vCSF) samples were collected from 35 patients with aSAH for up to 15 days. vCSF NF-L measurements were determined by enzyme-linked immunosorbent assay. NF-L levels were analysed in relation to acute clinical status, radiological findings and 6-month outcomes. RESULTS: vCSF NF-L concentrations were elevated in all patients with aSAH. Patients with early cerebral ischaemia (ECI), defined as a CT hypodense lesion visible within the first 3 days, had higher acute vCSF NF-L levels than patients without ECI. These elevated NF-L levels were similar in patients with ECI associated with intracranial haemorrhage and ECI associated with surgical/endovascular complications. vCSF NF-L levels did not differ as a function of acute clinical status, clinical vasospasm, delayed cerebral ischaemia or 6-month Glasgow Outcome Scale. CONCLUSIONS: Elevated vCSF NF-L levels may in part reflect increased injury to axons associated with ECI. However, our results suggest that axonal injury after aSAH as reflected by release of NF-L into the CSF may not play a major role in either secondary adverse events or long-term clinical outcomes.

Supratentorial juvenile pilocytic astrocytoma in a young adult with Silver-Russell syndrome.

Silver-Russell syndrome is a rare genetically heterogeneous disorder in which patients demonstrate intrauterine and postnatal growth retardation, triangular facies, excessive sweating during early childhood, late closure of the anterior fontanelle and skeletal asymmetry. An association with malignancy exists and only one previous intracranial tumour has been reported, a craniopharyngioma. We report the first case of Silver-Russell syndrome associated with a supratentorial juvenile pilocytic astrocytoma.

Adenoviral-mediated gene transfer in human and animal vein grafts using clinically relevant exposure times, pressures, and viral concentrations.

This study examined the efficiency of adenoviral-mediated gene transfer in experimental vein grafts and cultured human saphenous vein under physiologic conditions using clinically relevant exposure times, pressures, and viral concentrations. The external jugular veins of 25 male New Zealand White rabbits were exposed to 0.5 mL of replication-deficient adenovirus vectors encoding beta-galactosidase (AdlacZ), control adenovirus (AdBg/II), or vehicle at pressures ranging from 0 to 120 mmHg for 10 min. Veins were excised and grafted into the carotid circulation. After 5 days, the vessels were reexposed, excised, and stained with X-gal chromagen for beta-galactosidase (beta-gal) activity. Gene transfer was also performed in 13 segments of human saphenous vein discarded at the time of bypass grafting. The veins were cultured for 0-21 days and assayed for beta-gal activity as above. Rabbit vein grafts exposed to high-pressure AdlacZ transfection showed significant transgene expression in 100% of grafts (39 +/- 2% positive cells/hpf) while only 60% of those transfected at low pressure expressed beta-gal (9 +/- 3% positive cells/hpf). All human veins exposed to AdlacZ expressed beta-gal to a variable degree (range 10-50% positive cells/hpf). No control grafts or veins expressed the transgene. Efficient adenoviral-mediated gene transfer in experimental vein grafts and human saphenous vein segments can be achieved using clinically feasible parameters of exposure time, pressure, and viral concentration.

Effects of muscarinic and adrenergic agonism on auditory P300 in the macaque.

Homologs of human endogenous evoked potentials are known in several species of nonhuman primates, but the neurotransmitter substrates of these potentials remain uncertain. In particular, the role of central cholinergic and adrenergic systems is not yet clearly defined. We recorded cognitive evoked potentials from the scalp in four adult bonnet macaque monkeys during a passive version of the auditory oddball paradigm with unique novel stimuli under saline control conditions. In two subjects each, cognitive evoked potentials were also recorded following intramuscular administration of the m1 muscarinic agonist AF102B or of the alpha-2A noradrenergic agonist guanfacine. On saline, large positivities resembling the human P300 were recorded over midline sites in response to rare or novel auditory stimuli in all four monkeys. The amplitude of these positivities was sensitive to the delivery of fruit-juice reward in association with rare stimuli in three monkeys tested. At cognition-enhancing doses, AF102B enlarged the amplitude of P300-like positivities in both monkeys tested; guanfacine enlarged the amplitude of P300-like positivities in one of two monkeys tested. These results add to existing evidence of human-like endogenous late positivities in monkeys that are influenced by the cholinergic and adrenergic systems, and suggest a possible role of m1 muscarinic and alpha-2A noradrenergic receptor subtypes.

Divided attention-enhancing effects of AF102B and THA in aging monkeys.

The effects of cholinergic drugs proposed for treatment of cognitive impairment in normal aging and dementia on divided attention have been little studied in non-human primates. We tested the hypothesis that cholinergic drugs improve spatial divided attention in primates via a computer task requiring simultaneous tracking of two visual targets in three young and two aged healthy bonnet macaques. Task accuracy (number of correct responses) and reaction time (RT) were measured 2 h after administration of either the m1 agonist +/- -cis-2-methyl-spiro(1,3-oxathiolane-5,3')quinuclidine (AF102B; 0.1-2.1 mg/kg IM) or the cholinesterase inhibitor 9-amino-1,2,3,4-tetrahydroamino-acridine (THA; 0.5-2.0 mg/kg orally). Accuracy increased for four of five monkeys at appropriate doses of one or both cholinomimetics, accompanied in two monkeys by a drop in RT. Responses were less uniform to THA than to AF102B. For the five-monkey group at Best dose, accuracy increased 34% (THA) or 43% (AF102B) above baseline (P<0.05 for both drugs), respectively, with no significant change in RT and with minimal untoward effects. Cholinotherapy may improve divided attention in young and aged healthy primates.