Restorative Neurology and Neuroscience

{\it Purpose:} To improve functional recovery after peripheral nerve suture, we characterized the quality of target reinnervation in rats in which the afferent trigeminal connection to facial motoneurons had been altered.

{\it Methods:} Employing an improved lesion model and a refined mode of retrograde tracer application, we studied the accuracy of reinnervation in rats which underwent buccal-buccal nerve anastomosis (BBA) alone (group 1), BBA plus excision of the ipsilateral infraorbital nerve (ION; group 2), and BBA plus excision of the contralateral ION (group 3). This was done by comparison between the number of double-labeled motoneurons after pre-operative injection of Fluoro-Gold (FG) and post-operative injection of Fast Blue (FB) into the whisker pad muscles.

{\it Results:} In the first group we counted 398 ± 80 FG+FB double labeled cells (mean ± SD; n=9 rats), i.e., only 27% of all motoneurons that grew axons into the whisker pad had projected to these muscles before surgery. In group 2, this value was increased marginally to 436 ± 68 (32%). In group 3,. we counted 580 ± 63 double-labeled neurons. This is the first morphological report demonstrating significantly improved specificity of reinnervation. Indeed, 41% of the motoneurons innervating the target in group 3 belonged to the original neuron pool. These morphological findings are supported by evidence obtained from electrophysiological recordings and behavioural studies.

{\it Conclusions:} The principle finding of the present study is that a peripheral lesion to the contralateral trigeminal nerve improves the quality of reinnervation of the whisker pad musculature by its original nerve. The contralateral trigeminal lesion may trigger behavioural demand and forced overuse of the axotomized facial nerve, which may be a key issue for recovery of vibrissae rhythmical whisking after facial nerve surgery.

{\it Purpose:} 5-Lipoxygenase (5LOX) is an enzyme critical for leukotriene synthesis from arachidonic acid. In addition to its role in peripheral inflammation, this enzyme is also expressed in the brain but its functional role in the central nervous system is poorly understood. An upregulated expression of brain 5LOX, for example during aging and in multiple sclerosis, has been associated with increased vulnerability to neurodegeneration. Moreover, the 5LOX pathway has been associated with the neurotoxicity of the prion peptide. 5LOX-deficient mice [5LOX(-); B6129S$^{Alox5tm1Fun}$] and their controls (B6129SF2/J) have not been behaviorally characterized.

{\it Methods:} The following behavioral tests were used for behavioral characterization of 5LOX(-) mice: elevated plus-maze, marble burying, locomotor activity, rota-road, and the spontaneous alternations in T-maze.

{\it Results:} We found that in an elevated plus-maze, 5LOX(-) mice spent a shorter time in the "safe" closed arms, a longer time in the "anxiogenic" open arms, and entered the open arms more frequently. They also covered fewer marbles in the marble-burying anxiety test. No difference was observed between 5LOX(-) and 5LOX(+) mice in other tests.

{\it Conclusion:} These results indicate that 5LOX(-) mice are less prone to anxiety and point to a possible role for 5LOX in affective behaviors. We propose that creating congenic 5LOX(-) mice by backcrossing into inbred strains would provide additional tools to further elucidate this putative role.

{\it Purpose:} Receiving the Arm Ability Training for three weeks improves motor function among stroke patients with mild arm paresis. There is, however, a considerable variability in recovery among patients receiving the Arm Ability Training. The study investigated whether intersubject differences in movement-related electric brain activity explain the variability in motor recovery.

{\it Methods:} In a sample of 9 patients receiving the Arm Ability Training both motor performance using a standardised arm function test (TEMPA) and movement-related electric brain activity, i.e. slow cortical potentials (DC) as well as event-related desynchronisation of alpha (alpha-ERD) and beta activity (beta-ERD), were assessed before the Arm Ability Training was started. Stepwise multiple regression was used to establish the best predictive model for motor improvement scores (TEMPA difference from pre to post test three weeks later).

{\it Results:} Stepwise multiple regression indicated that electric brain activity during movement preparation explained the variance of motor improvement scores completely. Further, electric brain activity during movement as well as baseline motor performance accounted each for 50% of the variance of motor improvement scores.

{\it Conclusions:} Activation of sensorimotor areas during movement preparation and deactivation of other cortical areas during movement execution seem to be factors that predict a favourable outcome after training.

{\it Purpose:} The Arm Ability Training improves motor function among stroke and traumatic brain injury patients with mild arm paresis. There is, however, a considerable variability in motor recovery among patients receiving the Arm Ability Training. The study investigated whether psychological variables can explain the variability in motor recovery.

{\it Methods:} In a sample of 33 patients receiving the Arm Ability Training both motor performance (by use of the standardised arm function test TEMPA) and cognitive functions (attention, perceptual abilities, and learning) as well as depression were assessed before training was commenced. Both univariate correlational analyses and stepwise multiple regression were used to investigate these variables' ability to predict motor improvement (TEMPA difference scores from pre to post test after 3 weeks).

{\it Results:} The degree of motor dysfunction of the affected arm explained most (70%) of the variance of motor improvement scores of the standardised arm function test (TEMPA). Psychometric scores showed no or at the most weak associations with motor improvement (explaining at the most 10% of the variance).

{\it Conclusions:} Psychological variables had not been critical modifiers of motor recovery among stroke and traumatic brain injury patients with mild arm paresis receiving the Arm Ability Training.

{\it Purpose:} Recent research on the purine derivative of hypoxanthine Neotrofin™ (4-[[3-(1,6-dihydro-6-oxo-9-purin-9-yl)-1-oxopropyl]amino]benzoic acid; AIT-082) has indicated that Neotrofin treatment elevates the mRNA levels of various neurotrophic factors, including nerve growth factor (NGF), in the CNS. Several previous studies have indicated that NGF may regulate septodentate sprouting after entorhinal cortex lesions in rats. Thus, the objective of this investigation was to determine whether Neotrofin treatment would enhance lesion-induced septodentate sprouting from 4 to 15 days postlesion.

{\it Methods:} Sham-operated rats or rats with EC lesions were injected (i.p.) with either Neotrofin (30 mg/kg) or saline (0.9%) immediately after surgery and every day thereafter until the end of the treatment regimen. Septodentate sprouting, as indicated by intensity of acetylcholinesterase (AChE) label in the dentate gyrus, was assessed with optical densitometry.

{\it Results:} We observed that Neotrofin elevated the AChE-label in the outer molecular layer of the ventral dentate gyrus at 4 days postlesion and of the dorsal dentate gyrus at 15 days postlesion.

{\it Conclusions:} Neotrofin appears to have exerted limited stimulatory effects on lesion-induced sprouting by a cholinergic pathway.