Clarissa Pedrini Schuch

Neonatal hypoxia-ischemia induces attention-deficit hyperactivity disorder-like behavior in rats

Attention-deficit hyperactivity disorder (ADHD) may be caused by genetic or environmental factors. Among environmental factors, perinatal complications are related, such as neonatal hypoxia-ischemia (HI). Thus, the aim of this study was to investigate whether HI contributes to the development of characteristics related to ADHD in adult rats, and to correlate the behavioral results with brain damage volume. Male Wistar rats were divided into 2 groups: HI and control. The HI procedure consisted of a permanent occlusion of the right common carotid artery followed by a period of hypoxia (90 min; 8% O₂ and 92% N₂) on the 7th postnatal day. Two months later, animals were evaluated in the open field test during a single 5-min session, and in the 5-choice serial reaction time task (5-CSRTT), over 25 weeks. Our results demonstrated that animals submitted to HI manifest cognitive impairments in task acquisition, deficits in sustained attention, and increases in impulsivity and compulsivity in response to task manipulation in the 5-CSRTT. Locomotor activity observed in open field did not differ between groups. Moreover, brain volume loss in the total hemisphere, cerebral cortex, white matter, hippocampus, and striatum were observed in HI animals, especially on the side ipsilateral to the lesion. From these results, we can infer that neonatal HI is an environmental factor that could contribute to the development of behavioral characteristics observed in ADHD that are associated with general brain atrophy.

Time course of neuronal death following endothelin-1 induced focal ischemia in rats

BACKGROUND Endothelin-1 (ET-1) induced focal ischemia is increasingly being used as a preclinical model of stroke. Here, we described for the first time, the time course of neuronal death and infarct evolution during the first 7 days following ischemia. NEW METHOD We used hematoxylin and eosin (H&E) staining to evaluate infarct progression and Fluoro-Jade C (FJC) to quantify neuronal degeneration at 24, 48, 72h and 7 days after ET-1 injection to the forelimb motor cortex in Sprague-Dawley rats. RESULTS We found that infarct volume and neuronal degeneration are maximal at 24h post-stroke. Neuronal degeneration is also significantly reduced within 7 days of stroke induction. COMPARISON WITH EXISTING METHOD This study is the first to provide a direct evaluation of both infarct volume evolution and neuronal death time course following ET-1 induced focal ischemia in the forelimb motor cortex. CONCLUSION This study describes the short-term time course of neuronal death and brain injury in the ET-1 stroke model, which provides a significant reference when determining the appropriate time to commence neuroprotective or recovery promoting strategies.

Early environmental enrichment affects neurobehavioral development and prevents brain damage in rats submitted to neonatal hypoxia-ischemia

Our previous results demonstrated improved cognition in adolescent rats housed in environmental enrichment (EE) that underwent neonatal hypoxia-ischemia (HI). The aim of this study was to investigate the effects of early EE on neurobehavioral development and brain damage in rats submitted to neonatal HI. Wistar rats were submitted to the HI procedure on the 7th postnatal day (PND) and housed in an enriched environment (8th-20th PND). The maturation of physical characteristics and the neurological reflexes were evaluated and the volume of striatum, corpus callosum and neocortex was measured. Data analysis demonstrated a clear effect of EE on neurobehavioral development; also, daily performance was improved in enriched rats on righting, negative geotaxis and cliff aversion reflex. HI caused a transient motor deficit on gait latency. Brain atrophy was found in HI animals and this damage was partially prevented by the EE. In conclusion, early EE stimulated neurobehavioral development in neonate rats and also protects the neocortex and the corpus callosum from atrophy following HI. These findings reinforce the potential of EE as a strategy for rehabilitation following neonatal HI and provide scientific support to the use of this therapeutic strategy in the treatment of neonatal brain injuries in humans.

Enriched rehabilitation promotes motor recovery in rats exposed to neonatal hypoxia-ischemia.

Despite continuous improvement in neonatology there is no clinically effective treatment for perinatal hypoxia ischemia (HI). Therefore, development of a new therapeutic intervention to minimize the resulting neurological consequences is urgently needed. The immature brain is highly responsive to environmental stimuli, such as environmental enrichment but a more effective paradigm is enriched rehabilitation (ER), which combines environmental enrichment with daily reach training. Another neurorestorative strategy to promote tissue repair and functional recovery is cyclosporine A (CsA). However, potential benefits of CsA after neonatal HI have yet to be investigated. The aim of this study was to investigate the effects of a combinational therapy of CsA and ER in attempts to promote cognitive and motor recovery in a rat model of perinatal hypoxic-ischemic injury. Seven-day old rats were submitted to the HI procedure and divided into 4 groups: CsA+Rehabilitation; CsA+NoRehabilitation; Vehicle+Rehabilitation; Vehicle+NoRehabilitation. Behavioural parameters were evaluated pre (experiment 1) and post 4 weeks of combinational therapy (experiment 2). Results of experiment 1 demonstrated reduced open field activity of HI animals and increased foot faults relative to shams in the ladder rung walking test. In experiment 2, we showed that ER facilitated acquisition of a staircase skilled-reaching task, increased number of zone crosses in open-field exploration and enhanced coordinated limb use during locomotion on the ladder rung task. There were no evident deficits in novel object recognition testing. Delayed administration of CsA, had no effect on functional recovery after neonatal HI. There was a significant reduction of cortical and hemispherical volume and hippocampal area, ipsilateral to arterial occlusion in HI animals; combinational therapy had no effect on these morphological measurements. In conclusion, the present study demonstrated that ER, but not CsA was the main contributor to enhanced recovery of motor ability after neonatal HI.

Post-stroke kinematic analysis in rats reveals similar reaching abnormalities as humans

A coordinated pattern of multi-muscle activation is essential to produce efficient reaching trajectories. Disruption of these coordinated activation patterns, termed synergies, is evident following stroke and results in reaching deficits; however, preclinical investigation of this phenomenon has been largely ignored. Furthermore, traditional outcome measures of post-stroke performance seldom distinguish between impairment restitution and compensatory movement strategies. We sought to address this by using kinematic analysis to characterize reaching movements and kinematic synergies of rats performing the Montoya staircase task, before and after ischemic stroke. Synergy was defined as the simultaneous movement of the wrist and other proximal forelimb joints (i.e. shoulder, elbow) during reaching. Following stroke, rats exhibited less individuation between joints, moving the affected limb more as a unit. Moreover, abnormal flexor synergy characterized by concurrent elbow flexion, shoulder adduction, and external rotation was evident. These abnormalities ultimately led to inefficient and unstable reaching trajectories, and decreased reaching performance (pellets retrieved). The observed reaching abnormalities in this preclinical stroke model are similar to those classically observed in humans. This highlights the potential of kinematic analysis to better align preclinical and clinical outcome measures, which is essential for developing future rehabilitation strategies following stroke.

Changes in muscular activation patterns produced by a toning shoe during treadmill walking and quiet standing

Background: Recently a new shoe design with air compartments at the insole has been developed and termed as toning shoes. However, it is unclear how this air compartments-based shoe could affect muscle activation and centre of pressure during treadmill walking or quiet standing. Purpose: The aim of this study was to compare muscular activation during treadmill walking and quiet standing between toning shoes and regular shoes. Methods: Ten participants performed treadmill walking at 4.5 km.h−1 and unipodal standing wearing regular shoes and toning shoes in random order. Mean muscular activation of seven muscles from preferred lower limb (tibialis anterior, soleus, peroneus brevis, biceps femoris, gastrocnemius medialis, vastus lateralis, and rectus femoris) at different phases of the gait cycle (first half of contact, second half of contact and balance time) were assessed and compared between regular and toning shoes. Coefficient of variation and centre of pressure were calculated for temporal parameters and compared between regular and toning shoes. Principal results: Toning shoes led to higher coefficient of variation (20% during contact time; 15% during balance time), which may indicate a more unstable walking dynamic. Furthermore, the main muscular activation outcome was a 7% higher activation for rectus femoris and 7% lower activation for vastus lateralis at first half of contact time and higher activation for vastus lateralis (8%) and lower activation for rectus femoris (15%) at second half of contact time. Centre of pressure excursion and muscular activation during standing presented no significant differences. Conclusion: Toning shoe usage is increasing among the population and a better knowledge of effects on muscular activation and postural balance is fundamental. Toning shoes use resulted in a change in muscular activation during treadmill walking mainly for the quadriceps muscle. Some other muscle groups showed small differences in muscular activation patterns. There were no differences in postural balance and muscular activity during quiet standing with toning shoes use.