APOE epsilon3 gene transfer attenuates brain damage after experimental stroke.

Apolipoprotein E (apoE, protein; APOE, gene) is the major lipid-transport protein in the brain and plays an important role in modulating the outcome and regenerative processes after acute brain injury. The aim of the present study was to determine if gene transfer of the epsilon3 form of APOE improves outcome in a murine model of transient focal cerebral ischaemia. Mice received an intrastriatal injection of vehicle, a second-generation adenoviral vector containing the green fluorescent protein gene (Ad-GFP) or a vector containing the APOE epsilon3 gene (Ad-APOE) 3 days before 60 mins focal ischaemia. Green fluorescent protein expression was observed in cells throughout the striatum and subcortical white matter indicating successful gene transfer and expression. ApoE levels in the brain were significantly increased after Ad-APOE compared with Ad-GFP or vehicle treatment. Ad-APOE treatment reduced the volume of ischaemic damage by 50% compared with Ad-GFP or vehicle treatment (13+/-3 versus 29+/-4 versus 27+/-5 mm(3)). The extent of postischaemic apoE immunoreactivity was enhanced in Ad-APOE compared with Ad-GFP or vehicle treated mice. These results show the ability of APOE gene transfer to markedly improve outcome after cerebral ischaemia and suggest that modulating apoE levels may be a potential strategy in human stroke therapy.     

Primary orthostatic tremor is an exaggeration of a physiological response to instability.

Primary orthostatic tremor (POT) is a rare disorder characterised by an intense sense of unsteadiness upon standing and a 16-Hz tremor in which the timing between tremor bursts in different muscles (unilateral and bilateral) remains constant. Hitherto, similar EMG activity has not been described in healthy subjects and it has been postulated that the oscillations seen in POT are primarily pathological. In this study, EMG was recorded from tibialis anterior in healthy subjects who were made unsteady through vestibular galvanic stimulation or leaning backwards. Under these conditions, a peak at approximately 16 Hz was seen in the coherence between the left and right tibialis anterior. This bilateral coherence was absent when the subjects activated the same muscles when not unsteady. These data indicate the existence of a physiological system involved in organising postural responses under circumstances of imbalance and characterised by a highly synchronised output at approximately 16 Hz. In addition, the results suggest that the core abnormality in POT may be an exaggerated sense of unsteadiness when standing still, which then elicits activity from a 16-Hz oscillator normally engaged in postural responses.