Recovery of slow skeletal muscle after injury in the senescent rat

We studied the contractile, histological and biochemical characteristics of regenerating slow (soleus) muscles of aged rats and the effect of IGF-1 treatment on these parameters. Regenerating soleus muscles were studied 21 days after myotoxic injury. In senescent rats (24 month old), the in situ isometric maximal tetanic force (P0), resistance to fatigue (T20%P0) and shortening speed with an afterload of 20%P0 (SS20%P0) were lower (p<0.05) in regenerating soleus muscles as compared to uninjured controlateral soleus muscles. Moreover, the expression of type 1 myosin heavy chain (MHC-1) was decreased by injury in the soleus muscles of senescent rats (p<0.05). Furthermore, a single injection of IGF-1 (3 microg) into the soleus of senescent rats only slightly increased the level of sarcoplasmic reticulum type 2 Ca(2+)-ATPase in regenerating soleus muscles (p<0.01). Contrary to senescent animals, regenerating soleus of adult rats (10 month old) did not present significantly lower P0 and MHC-1 expression than uninjured controlateral muscles (p>0.05). In conclusion, the regeneration of a slow muscle is more uncompleted 3 weeks after myotoxic injury in senescent rats than in adult rats. It cannot be made more effective by a single injection of IGF-1 into the senescent slow muscle.     

Hippocampal function and visual object processing in temporal lobe epilepsy

Limbic event-related potentials related to verbal but not to visual recognition memory have been found to be attenuated within the epileptic hippocampus of patients with temporal lobe epilepsy (TLE). To identify hippocampal contributions to visual processing and memory we recorded intracranial ERPs directly from within the epileptic and the non-epileptic hippocampus in 12 patients with unilateral TLE during a visual object decision and naming task. While the non-epileptic hippocampus differentiated reliably between real and nonsense objects, this effect was completely eliminated within the epileptic mesial temporal lobe. This finding suggests that the hippocampus proper contributes to the semantic processing of visual objects and may help to explain visual memory deficits in TLE.     

Directed migration of neuronal precursors into the ischemic cerebral cortex and striatum

Pathological processes, including cerebral ischemia, can enhance neurogenesis in the adult brain, but the fate of the newborn neurons that are produced and their role in brain repair are obscure. To determine if ischemia-induced neuronal proliferation is associated with migration of nascent neurons toward ischemic lesions, we mapped the migration of cells labeled by cell proliferation markers and antibodies against neuronal marker proteins, for up to 2 weeks after a 90-min episode of focal cerebral ischemia caused by occlusion of the middle cerebral artery. Doublecortin-immunoreactive cells in the rostral subventricular zone, but not the dentate gyrus, migrated into the ischemic penumbra of the adjacent striatum and, via the rostral migratory stream and lateral cortical stream, into the penumbra of ischemic cortex. These results indicate that after cerebral ischemia, new neurons are directed toward sites of brain injury, where they might be in a position to participate in brain repair and functional recovery.     

The magnitude and the extinction duration of the cocaine-induced conditioned locomotion-activated response are related to the number of cocaine injections paired with the testing context in C57BL/6J mice

Behavioural activation repeatedly induced by a stimulant in rodents can persist in the absence of the drug if the animals are tested in the context where the drug was previously given, a phenomenon often explained in terms of Pavlovian conditioning. The aim of this study was to verify whether the amplitude of the putative CR (the drug-like activity) increases with the number of the US-CS associations (the number of drug-context pairings), one of the most representative rules of Pavlovian conditioning. The effect of the number of trials on the speed of extinction was also considered. C57BL/6J mice received 3, 6 or 12 once-daily injections of either saline or 12 mg/kg (-)-cocaine hydrochloride (s.c.) in the same test context, a photocell activity-box in which they were tested for 60 min after every injection. Other groups received the same treatments outside of the test context (being placed in a novel cage tub after each injection). Twenty-four hours after the last treatment session, all mice were challenged with saline in the test context (test for conditioned activity), extinction sessions taking place on the three subsequent days. Sensitisation to the locomotor-activating effect of cocaine developed only amongst the animals injected 6 or 12 times, the magnitude of the last sensitised response being comparable for these two injections regimen. On saline challenge, only the animals that had received 6 or 12 cocaine injections showed significant conditioned activity (CR), with the greatest response occurring following 12 injections. The 6-trial group reached the level of non-significance after fewer extinction sessions than the 12-trial group; however, the rates of extinction did not differ (comparable regression coefficients and quasi-parallel curves). These results suggest that the amplitude of the CR (cocaine-like stimulation after saline), and perhaps less convincingly the duration of extinction, are functions of the number of the US-CS (cocaine-context) pairings, supporting the Pavlovian nature of post-sensitisation placebo drug-like effects.     

Directional interference during bimanual coordination: is interlimb coupling mediated by afferent or efferent processes

The role of afferent information in bimanual directional interference was studied by means of a modulation of the response-produced information in one of both limbs. In Experiment 1, visual information was either present, withdrawn, or shown with a directional transformation on a LCD screen. In Experiment 2, the technique of muscle tendon vibration was used to bias the kinesthetic afferent information associated with movement. The findings revealed strong evidence for directional interference between both limbs. Nevertheless, no evidence could be advanced that the observed interference from the right onto the left limb movement was modulated by manipulation of the afferent sources of information. It is concluded that directional interference primarily emerges at the efferent level of movement planning and organization.     

A direct prefrontotectal tract against distractibility in the human brain

Distractibility, which can be defined as an attention deficit in which orientation toward irrelevant targets can be hardly inhibited, is commonly related to a dysfunction of the dorsolateral prefrontal cortex. Here, we show that increased distractibility, observed in a patient with an exceptionally small lesion located in the upper brainstem, may result from the interruption of a direct tract that connects the prefrontal cortex to the superior colliculus, a structure involved in both eye movement control and attentional shifts.     

Enhancing the sensitivity of a sustained attention task to frontal damage: convergent clinical and functional imaging evidence

Despite frequent reports of poor concentration following traumatic brain injury, studies have generally failed to find disproportionate time-on-task decrements using vigilance measures in this patient group. Using a rather different definition, neuropsychological and functional imaging research has however linked sustained attention performance to right prefrontal function--a region likely to be compromised by such injuries. These studies have emphasised more transitory lapses of attention during dull and ostensibly unchallenging activities. Here, an existing attention measure was modified to reduce its apparent difficulty or 'challenge'. Compared with the standard task, its capacity to discriminate traumatically head-injured participants from a control group was significantly enhanced. Unlike existing functional imaging studies, that have compared a sustained attention task with a no-task control, in study 2 we used positron emission tomography to contrast the two levels of the same task. Significantly increased blood flow in the dorsolateral region of the right prefrontal cortex was associated with the low challenge condition. While the results are discussed in terms of a frontal system involved in the voluntary maintenance of performance under conditions of low stimulation, alternative accounts in terms of strategy application are considered.     

IL-11 and IL-17 expression in nasal polyps: relationship to collagen deposition and suppression by intranasal fluticasone propionate

OBJECTIVES/HYPOTHESIS: Chronic hyperplastic sinusitis (CHS) with nasal polyps (NP) is characterized by extensive mucosal thickening, goblet cell hyperplasia, and subepithelial fibrosis. These features are described to be part of remodeling in the lower airways. The cytokines interleukin (IL)-11 and IL-17 are believed to play a role in lower airway remodeling, but there has been very little work so far examining these cytokines and their relationship to fibrosis in CHS/NP. The aims of this study were to examine the deposition of collagens types I, III, and V in CHS/NP, evaluate the relationship of collagen deposition to expression of IL-11 and IL-17, and to examine the effect of treatment with intranasal fluticasone on these features. STUDY DESIGN: Sixteen subjects were included in this double-blind, placebo-controlled study. NP biopsies were obtained at the baseline and after 4 weeks of treatment with intranasal fluticasone propionate (FP, Flonase) or placebo. Normal control middle turbinate biopsies from eight nonallergic subjects without sinusitis were used as a control for cytokine and collagen expression. METHODS: Tissues were assessed for deposition of collagen types I, III, and V using immunocytochemistry. The expression of the cytokines IL-11 and IL-17 was examined by immunostaining or in situ hybridization. The pre- to posttreatment results were analyzed using paired t test, and the magnitude of changes were estimated using one-way analysis of variance (ANOVA) statistical test followed by least significance difference post hoc comparisons of means. RESULTS: Compared with normal control nasal turbinate tissues, collagen types I, III, and V were increased in all NP tissues, with a predominance of types III and V. Collagen deposition was most abundant in the submucosal connective tissue and in the basement membrane zone. FP treatment had no significant effect on deposition of any collagen type. Expression of IL-11 and IL-17 was also greatly increased in NP compared with control nasal turbinate tissues. IL-11 expression was observed in both inflammatory cells and the epithelium, whereas IL-17 expression was primarily associated with inflammatory cells. In the pretreatment NP, a correlation was found between the presence of IL-11 and collagen type I (r = 0.59, P =.02) and also between IL-17 and both CD4+ and CD8+ T lymphocytes (r = 0.52, P =.05; r = 0.60, P =.02, respectively). Treatment with FP significantly reduced IL-11 expression in subepithelial inflammatory cells and in the epithelial compartment. In contrast, although IL-17 expression was reduced by FP, this effect did not reach statistical significance. CONCLUSION: NP manifest an increased expression of collagen types III, V, and I and an increase in profibotic cytokines IL-11 and IL-17. A correlation exists between deposition of collagen type I and expression of IL-11, suggesting a possible role for IL-11 in NP remodeling. Collagen deposition was not reversed by FP treatment, whereas IL-11 expression was suppressed. These results are consistent with a partial insensitivity of NP to FP treatment but also suggest that longer-term treatment or perhaps earlier intervention with FP might reduce proinflammatory cytokine signals and ultimately have a beneficial effect in preventing airway remodeling in NP.