RESUMEN

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic-ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.

Asunto(s)

Biomarcadores , Electroencefalografía , Hipoxia-Isquemia Encefálica , Estimulación Luminosa , Animales , Hipoxia-Isquemia Encefálica/fisiopatología , Hipoxia-Isquemia Encefálica/metabolismo , Ratas , Biomarcadores/metabolismo , Masculino , Modelos Animales de Enfermedad , Femenino , Ratas Sprague-Dawley , Isoflurano/farmacología , Oxitocina/farmacología , Oxitocina/metabolismo , Humanos

RESUMEN

The synchronization of neuronal activity in the sensorimotor cortices is crucial for motor control and learning. This synchrony can be modulated by upstream activity in the cerebello-cortical network. However, many questions remain over the details of how the cerebral cortex and the cerebellum communicate. Therefore, our aim is to study the contribution of the cerebellum to oscillatory brain activity, in particular in the case of dystonia, a severely disabling motor disease associated with altered sensorimotor coupling. We used a kainic-induced dystonia model to evaluate cerebral cortical oscillatory activity and connectivity during dystonic episodes. We performed microinjections of low doses of kainic acid into the cerebellar vermis in mice and examined activities in somatosensory, motor and parietal cortices. We showed that repeated applications of kainic acid into the cerebellar vermis, for five consecutive days, generate reproducible dystonic motor behavior. No epileptiform activity was recorded on electrocorticogram (ECoG) during the dystonic postures or movements. We investigated the ECoG power spectral density and coherence between motor cortex, somatosensory and parietal cortices before and during dystonic attacks. During the baseline condition, we found a phenomenon of permanent adaptation with a change of baseline locomotor activity coupled to an ECoG gamma band increase in all cortices. In addition, after kainate administration, we observed an increase in muscular activity, but less signs of dystonia together with modulations of the ECoG power spectra with an increase in gamma band in motor, parietal and somatosensory cortices. Moreover, we found reduced coherence in all measured frequency bands between the motor cortex and somatosensory or parietal cortices compared to baseline. In conclusion, examination of cortical oscillatory activities in this animal model of chronic dystonia caused by cerebellar dysfunction reveals a disruption in the coordination of neuronal activity across the cortical sensorimotor/parietal network, which may underlie motor skill deficits.