A behavioural characterisation of the FVB/N mouse strain.

The use of transgenic models in scientific research has made an enormous contribution to our understanding of the causes and symptoms of many diseases, including neurodegenerative conditions such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). In the creation of transgenic models of neurodegenerative disease, effects of the background strain of the animal on the resulting genotype must be taken into consideration. This is particularly true for behavioural studies in which the background strain of the mouse may mask the phenotype of the genetic manipulation. Here, the behaviour of two mouse strains used in transgenic models, FVB/N and C57BL6/J, were compared. Studies of circadian wheel activity, cognition and aggression revealed considerable phenotypic differences between strains. These data also indicate that the FVB/N strain is not appropriate as a background strain in the behavioural assessment of transgenic mouse models.

A delayed class of BOLD waveforms associated with spreading depression in the feline cerebral cortex can be detected and characterised using independent component analysis (ICA).

An application of independent component analysis to blood oxygenation level- dependent MRI (BOLD-MRI) results was used to detect cerebrovascular changes that followed the initiation of cortical spreading depression (CSD) in feline brain. The cortical images were obtained from a horizontal plane at 28 s intervals before, and for 1.4-1.75 h after, KCl dissolved in agar (KCl/agar) had been directly applied to the left suprasylvian gyrus of 13 anesthetized cats for 10 min. It successfully resolved, for the first time, a novel class of prolonged, and delayed, biphasic BOLD waveforms. These were larger in amplitude ( approximately 20%), longer lasting and more delayed in onset (13-33 min) than the brief propagating (90 s) BOLD increase ( approximately 4%) already known to be associated with CSD on earlier occasions. Furthermore, such changes occurred in localized regions on the hemisphere ipsilateral to the site of stimulus application in 4 out of 5 control subjects rather than themselves generating propagating waves. Finally, the biphasic waveforms were consistently abolished in the 4 experimental animals studied following the i.v. administration of sumatriptan (0.3 mg kg(-1)), an antimigraine 5-HT(1B/1D) agonist, 15 min before the application of the transient stimulus. They were abolished in 2 out of 4 animals following the intraperitoneal (i.p.) administration of SB-220453 (tonabersat: 10 mg kg(-1), 90 min before stimulus application), a novel anticonvulsant that has recently been reported to inhibit CSD. ICA has thus been successful in detecting a novel localized, as opposed to propagating, signal of potential physiological significance hidden in complex BOLD- MRI data, whose sensitivity to sumatriptan may relate it to the cerebrovascular changes reported in the headache phase of migraine.

Cortical spreading depression in the feline brain following sustained and transient stimuli studied using diffusion-weighted imaging.

Cortical spreading depression (CSD) was induced by transient (10 min) applications of KCl in agar upon the cortical surface of alpha-chloralose anaesthetised cats. Its features were compared with CSD resulting from sustained applications of crystalline KCl through a mapping of the apparent diffusion coefficient (ADC) using diffusion-weighted echo planar imaging (DWI) over a poststimulus period of 60-100 min. Individual CSD events were computationally detected with the aid of Savitzky-Golay smoothing applied to critically sampled data derived from regions of interest (ROIs) made up of 2 x 2 pixel matrices. The latter were consistently placed at three selected sites on the suprasylvian gyrus (SG) and six sites on the marginal gyrus (MG). The CSD events thus detected were then quantitatively characterised for each ROI using the original time series. Both stimuli consistently elicited similar spreading patterns of initial, primary CSD events that propagated over the SG and marginal MG and were restricted to the hemispheres on which the stimuli were applied. There followed secondary events over smaller extents of cortical surface. Sustained stimuli elicited primary and secondary CSD events with similar amplitudes of ADC deflection that were distributed around a single mean. The ADC deflections were also conserved in peak amplitude throughout the course of their propagation. The initial primary event showed a poststimulus latency of 1.1 +/- 0.1 min. Successive secondary events followed at longer, but uniform, time intervals of around 10 min. Primary and secondary CSDs showed significantly different velocities of conduction (3.32 +/- 0.43 mm min(-1) vs. 2.11 +/- 0.21 mm min(-1), respectively; n = 5) across the cerebral hemisphere. In contrast, transient stimuli produced significantly fewer numbers of CSD events (3.8 +/- 0.5 events per animal, n = 5) than did sustained stimuli (7.4 +/- 0.5 events per animal, mean +/- S.E.M., n = 5, P = 0.002). The peak ADC deflection of their primary CSD events declined by approximately 30 % as they propagated from their initiation site to the interhemispheric boundary. The primary CSD event following a transient stimulus showed a latency of 1.4 +/- 0.1 min. It was followed by successive and smaller secondary ADC deflections that were separated by progressively longer time intervals. Conduction velocities of secondary events were similar to those of primary events. Conduction velocities of both primary and secondary events were slower than their counterparts following a sustained stimulus. ADC changes associated with CSD thus persist at times well after stimulus withdrawal and vary markedly with the nature of the initiating stimulus even in brain regions remote from the stimulus site.