Obstructive sleep apnea (OSA) is a frequent medical condition and is associated with cognitive impairments in adults and with hyperactivity and decreased school performance in children. In an adult rodent model, intermittent hypoxia (IH), such as occurs in OSA, is associated with neurodegenerative changes in the hippocampus and cortex and with spatial learning deficits. Because a unique developmental window of neural vulnerability to IH is present, we hypothesized that exposure to IH throughout the vulnerable ages would result in increased behavioral impairments in the juvenile rat. Rat pups were therefore exposed to either room air or IH beginning at postnatal (PN) d 10 until PN d 30. Learning and memory were assessed via a standard place-training version of the Morris water maze beginning at PN d 25. Locomotor activity was assessed on PN d 29 and 30. Pups exposed to IH displayed significant spatial learning impairments, and exposed male rats but not female rats displayed increased locomotor activity in the open field. Collectively, these findings indicate that exposure to IH at an age that corresponds to the peak incidence of OSA in children induces substantial learning impairment and gender-dependent behavioral hyperactivity in the juvenile rat. We postulate that this novel experimental model may allow for future exploration of mechanisms underlying the neurobehavioral deficits of children with OSA.

Abstract-Clinical interventions to restore standing or stepping by using nerve cuff stimulation require a detailed knowledge of femoral nerve neuroanatomy. We harvested eight femoral nerves with all distal branches and characterized the branching patterns and diameters. The fascicular representation of each distal nerve was identified and traced proximally to create fascicle maps of the compound femoral nerve in four cadaver specimens. Distal nerves were consistently represented as individual fascicles or distinct groups of fascicles in the compound femoral nerve. Branch-free length of the compound femoral nerve was 1.50 +/-0.47 cm (mean +/-standard deviation). Compound femoral nerve cross sections were noncircular with major and minor diameters of 10.50 +/-1.52 mm and 2.30 +/-0.63 mm, respectively. In vivo intraoperative measurements in six subjects were consistent with cadaver results. Selective stimulation of individual muscles innervated by the femoral nerve may therefore be possible with a single neural prosthesis able to selectively stimulate individual groups of fascicles.

Intermittent hypoxia (IH), one of the hallmarks of obstructive sleep apnea, occurs more frequently during pregnancy. We hypothesized that IH may lead to persistent postnatal changes in respiratory responses to acute hypoxia and may also lead to adverse effects on spatial function learning as revealed by the Morris water maze. To examine this issue, time-pregnant Sprague-Dawley rats were exposed to IH and room air (IHRA; 21 and 10% O2 alternations every 90 seconds) or to normoxia (RARA) until delivery. Ventilatory and metabolic responses to a 20-minute acute hypoxic challenge (10% O2) were conducted at postnatal ages 5, 10, 15, and 30 days. In addition, spatial task learning was assessed in the water maze at 1 and 4 months of age. Normoxic ventilation was higher at all time points in IHRA rats than in RARA rats (p < 0.01). Peak hypoxic ventilatory responses were attenuated in IHRA rats at 5 days of age and hypoxic ventilatory depression was accentuated at this age as well. However, ventilatory equivalents (minute ventilation/oxygen consumption) revealed significant reductions in peak hypoxic ventilatory responses of IHRA rats and hypoxic ventilatory depression at all postnatal ages (p < 0.01). Acquisition and retention of a spatial task were similar in the IHRA and RARA groups at both 1 and 4 months of age. We conclude that gestational intermittent hypoxia elicits long-lasting alterations in the control of breathing. We postulate that such IH-induced respiratory plasticity may create selective vulnerability to hypoxia during development.

Intermittent hypoxia (IH) during sleep, such as occurs in obstructive sleep apnea, leads to degenerative changes in the hippocampus, and is associated with spatial learning deficits in the adult rat. We report that in Sprague-Dawley rats the initial IH-induced impairments in spatial learning are followed by a partial functional recovery over time, despite continuing IH exposure. These functional changes coincide with initial decreases in basal neurogenesis as shown by the number of positively colabelled cells for BrdU and neurofilament in the dentate gyrus of the hippocampus, and are followed by increased expression of neuronal progenitors and mature neurons (nestin and BrdU-neurofilament positively labelled cells, respectively). In contrast, no changes occurred during the course of IH exposures in the expression of the synaptic proteins synaptophysin, SNAP25, and drebrin. Collectively, these findings indicate that the occurrence of IH during the lights on period results in a biphasic pattern of neurogenesis in the hippocampus of adult rats, and may account for the observed partial recovery of spatial function.