Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated AB (1-42) injections in the rat

It has been suggested that inflammatory processes may play a role in the development of Alzheimerâ??s disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 μl of aggregated β-amyloid (Aβ) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 μl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Aβ injections. Withdrawal of ibuprofen treatment from aggregated Aβ-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Aβ-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Aβ injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.

Neuromuscular and biomechanical factors codetermine the solution to motor redundancy in rhythmic multijoint arm movement

How the CNS deals with the issue of motor redundancy remains a central question for motor control research. Here we investigate the means by which neuromuscular and biomechanical factors interact to resolve motor redundancy in rhythmic multijoint arm movements. We used a two-df motorised robot arm to manipulate the dynamics of rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow-joint complex. Participants were required to produce rhythmic FE and SP movements, either in isolation, or in combination (at the phase relationship of their choice), while we recorded the activity of key bi-functional muscles. When performed in combination, most participants spontaneously produced an in-phase pattern of coordination in which flexion is synchronised with supination. The activity of the Biceps Brachii (BB), the strongest arm muscle which also has the largest moment arms in both flexion and supination was significantly higher for FE and SP performed in combination than in isolation, suggesting optimal exploitation of the mechanical advantage of this muscle. In a separate condition, participants were required to produce a rhythmic SP movement while a rhythmic FE movement was imposed by the motorised robot. Simulations based upon a musculoskeletal model of the arm demonstrated that in this context, the most efficient use of the force-velocity relationship of BB requires that an anti-phase pattern of coordination (flexion synchronized with pronation) be produced. In practice, the participants maintained the in-phase behavior, and BB activity was higher than for SP performed in isolation. This finding suggests that the neural organisation underlying the exploitation of bifunctional muscle properties, in the natural context, constrains the system to maintain the