Effects of obstructive sleep apnea on autonomic cardiac control during sleep.

INTRODUCTION: The present study investigated whether autonomic control of the heart for persons with low and high levels of sleep apnea/hypopnea differed between sleep stages and across the sleep period. DISCUSSION: Electrocardiography and impedance cardiography of 24 patients referred to polysomnography were recorded through the night. A mixed repeated-measures and between-subjects, quasi-experimental design was utilized. Heart period, high frequency heart rate variability, and pre-ejection period were computed, respectively, as measure of heart rate and estimates of parasympathetic and sympathetic control. The cardiac and autonomic measures for participants with low apnea-hypopnea indices were compared to those of patients with high rates of apnea-hypopnea across the sleep period and sleep stages. Cardiac rates of the two groups decreased incrementally through the sleep period. Cardiovascular measures during sleep from the group with high rates of apnea-hypopnea indicated larger parasympathetic activation in relation to wake baseline for epochs without arousals than from the group with low apnea-hypopnea rates. Parasympathetic activation during nonrapid-eye movement (non-REM) sleep (sleep stage 2) was significantly greater than during REM sleep. Higher levels of apnea-hypopnea seem to be associated with increased parasympathetic control, especially during lighter, non-REM sleep. A possible explanation for this phenomenon is a compensatory response to oxygen desaturation caused by disturbed breathing.

The novel substituted pyrimidine, KP544, reduces motor deficits in the R6/2 transgenic mouse model of Huntington's disease.

PURPOSE: The purpose of this study was to test the potential therapeutic effects of the substituted pyrimidine, KP544, which has been shown to amplify the effects of nerve growth factor in vitro, on motor deficits in the R6/2 transgenic mouse model of Huntington's disease (HD). METHODS: Young, female R6/2 mice were given daily oral intubation of either 10 mg/kg KP544 or vehicle (0.5% methylcellulose) at 6 weeks of age and tested from postnatal weeks 8 through 12 on a battery of motor tasks, including assessments of clasping (drawing of the limbs to the torso when suspended by the tail), motor coordination on the rotarod, and spontaneous motor activity in the open-field. Following testing, the mice were sacrificed and the brains were sectioned and stained with cresyl violet for histological examination. RESULTS: KP544 treatment decreased balance deficits on the rotarod task, reduced clasping, delayed the onset of hypoactivity, and reduced enlargement of the lateral ventricles in R6/2 mice. CONCLUSION: These results suggest that KP544 can reduce motor deficits and anatomical alterations in R6/2 mice. Further research into the use of KP544 as a potential pharmacotherapy HD is warranted.

Neural progenitor cell transplants promote long-term functional recovery after traumatic brain injury.

Studies demonstrating the versatility of neural progenitor cells (NPCs) have recently rekindled interest in neurotransplantation methods aimed at treating traumatic brain injury (TBI). However, few studies have evaluated the safety and functional efficacy of transplanted NPCs beyond a few months. The purpose of this study was to assess the long-term survival, migration, differentiation and functional significance of NPCs transplanted into a mouse model of TBI out to 1 year post-transplant. NPCs were derived from E14.5 mouse brains containing a transgene-expressing green fluorescent protein (GFP) and cultured as neurospheres in FGF2-containing medium. Neurospheres were injected into the ipsilateral striatum of adult C57BL/6 mice 1 week following unilateral cortical impact injury. Behavioral testing revealed significant improvements in motor abilities in NPC-treated mice as early as 1 week, and the recovery was sustained out to 1 year post-transplant. In addition, mice receiving NPC transplants showed significant improvement in spatial learning abilities at 3 months and 1 year, whereas an intermediate treatment effect on this behavioral parameter was detected at 1 month. At 14 months post-transplant, GFP(+) NPCs were observed throughout the injured hippocampus and adjacent cortical regions of transplanted brains. Immunohistochemical analysis revealed that the majority of transplanted cells co-labeled for NG2, an oligodendrocyte progenitor cell marker, but not for neuronal, astrocytic or microglial markers. In conclusion, transplanted NPCs survive in the host brain up to 14 months, migrate to the site of injury, enhance motor and cognitive recovery, and may play a role in trophic support following TBI.

Spatial learning deficits and emotional impairments in pentylenetetrazole-kindled rats.

Pentylenetetrazole (PTZ) is a chemical kindling agent used to examine the efficacy of potential anticonvulsants in rats. However, the extent to which PTZ mimics postseizure symptoms of epilepsy has not been thoroughly examined. This study assessed whether PTZ-induced seizures produce cognitive and emotional deficits that mimic those observed in many epileptic patients. Rats were given 30mg/kg PTZ or vehicle (intraperitoneally) every other day for 28 days. Those rats exhibiting consistent seizure activity were tested for learning ability and emotional reactivity, beginning 1 week following a single challenge dose of PTZ. Rats given PTZ made more reference memory errors in a radial arm water maze task, and exhibited emotional abnormalities in the forced swim test, the systematic handling test, and the open-field exploratory maze. Histological analysis revealed neuronal loss in the CA1 area and increased mossy fiber sprouting in the dentate gyrus, similar to what is observed in human epilepsy. These results indicate that PTZ kindling provides a useful model of postseizure dysfunction, which can serve as a screen for potential treatments for those cognitive, emotional, and neuropathological deficits that resemble those symptoms observed in human epilepsy.