Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and alpha7beta1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system.

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BackgroundSleep pattern is an important factor in a child’s mental, behavioural and physical status. To evaluate the sleep patterns of children, subjective tools such as sleep logs and questionnaires are still widely used in addition to objective methods of sleep assessment. Despite the established correlation between subjective and objective sleep variables, the characteristic features of subjective assessment have not been elucidated.MethodsTo investigate the characteristics of parental sleep assessment (daily sleep log and brief questionnaire) in preschool children, a 7-day actigraphic sleep study was conducted in 48 healthy 5-year-old children.ResultsSleep schedule variables in the parental reports generally correlated well with actigraphic assessment of sleep patterns; however, sleep periods were longer in parental reports than in actigraphic recordings. Although the daily sleep log was better correlated with actigraphy, the brief questionnaire showed a good correlation with sleep pattern on weekday actigraphic assessments. Parental reports recorded fewer than 10% of the night wakings recorded by actigraphy.ConclusionsSubjective sleep assessments remain useful, although their utility depends on the purpose and size of the study in question. However, knowledge of the potential biases and characteristics of such assessments is essential for correct interpretation of the data.

In a cohort of very preterm born infants, abnormal white matter appearance on term MRI showed consistent associations with cognitive impairments at 9 years old, further supporting the benefit of obtaining term MRI for very preterm born infants.

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Under physiologic conditions, brain intracellular pH (pH i ) is maintained at 7.03. Rebound brain intracellular alkalosis has been observed in experimental models and adult stroke after hypoxia/ ischemia (HI). In term infants with neonatal encephalopathy (NE), an association exists between the magnitude of brain alkalosis and neurodevelopmental outcome, and there is increasing evidence to suggest that alkalosis may be deleterious to cell survival. Activation of the Na ϩ /H ϩ exchanger (NHE) is thought to be responsible for the rapid normalization of pH i and rebound alkalosis after reperfusion. We hypothesized that N-methyl-isobutyl-amiloride (MIA), an inhibitor of the NHE, would reduce brain injury in a model of neonatal HI. Seven-day-old mice underwent left carotid artery occlusion followed by exposure to 8% oxygen for 30 min (moderate insult) or 1 h (severe insult). Animals received MIA or saline 8 hourly starting 30 min before HI. Outcome was determined at 48 h by measuring viable tissue in the injured hemisphere (severe insult) or injury score and TUNEL staining (moderate insult). After the severe insult, MIA had a significant neuroprotective effect increasing forebrain tissue survival from 44% to 67%. After the moderate insult, damage was localized to the hippocampus where treatment resulted in a significant reduction in injury score and in TUNEL-positive cells. MIA was also shown to have a significant overall neuroprotective effect based on injury score after the moderate insult. Amiloride analogues are neuroprotective when commenced before HI in a mouse model. P erinatal HI affects approximately one to two per 1000 term infants per year in the United Kingdom and leads to death or severe impairment in more than 750 infants annually (1) Over the past 20 y, studies using phosphorus ( 31 P) and ( 1 H) proton magnetic resonance spectroscopy (MRS) in both infants with NE (2-4) and experimental models (5,6) have characterized the biphasic disruption of cerebral energetics that occurs in the hours after HI. These observations have led to the concept of a "therapeutic window" after HI, during which intervention may ameliorate the severity of brain injury. Recent results from the first randomized trials of mild hypothermia in term infants with NE are promising (7-9); however, considerable work is still required to optimize cooling strategies in the newborn. Furthermore, there is a growing impression that optimum neuroprotection may involve the use of more than one therapy, targeting different parts of the neurotoxic cascade.Under physiologic conditions, brain pH i is maintained at approximately 7.03; the NHE tightly regulates both pH i and cell volume by extruding protons from and taking sodium up into cells (10). A remarkable observation from the studies employing 31 P MRS in infants with NE was that during the secondary phase of energy decline occurring from 8 to 24 h after birth, brain pH i was not acidic but alkaline (pH i 7.1-7.4) (11). Some evidence suggests that excessive activation of the NHE aft...

Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system.