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Objective: This systematic review evaluated the effectiveness of two frequency-lowering schemes, non-linear frequency compression and frequency transposition, at improving speech intelligibility for adult hearing-impaired populations., Design: A systematic search of 10 electronic databases was carried out using pre-defined inclusion criteria. Accepted articles were then critically appraised using the Effective Public Health Practice Project (EPHPP) Critical Appraisal Tool. Outcome results were further synthesised where possible using random effects meta-analysis to provide overall combined estimates of the treatment differences along with 95% confidence intervals., Study Sample: A total of 20 articles were accepted for final review., Results: Overall, study quality was of moderate strength. Meta-analysis found a statistically significant benefit in favour of frequency-lowering for consonant recognition testing in quiet across 145 participants with both algorithms providing comparable gains. Equivalent results were found between frequency-lowering and conventional processing on all other speech measures., Conclusions: Based on the available data, frequency-lowering does seem to provide some improvement in an individual's speech intelligibility dependant on the stimulus type, although the benefits were modest. This improvement was not seen across all measures, however those who do not benefit from the technology will also not be harmed by trialling it.

Objective: Estrogen receptors are present within the fetal brain, suggesting that estrogens may exert an influence on cerebral development. Loss of placentally derived estrogen in preterm birth may impair development., Study Design: Baboons were delivered at 125 days of gestation (term approximately 185 days), randomly allocated to receive estradiol (n = 10) or placebo (n = 8), and ventilated for 14 days. Brains were assessed for developmental and neuropathological parameters., Results: Body and brain weights were not different between groups, but the brain/body weight ratio was increased (P < .05) in estradiol-treated animals. There were no differences (P > .05) between groups in any neuropathological measure in either the forebrain or cerebellum. There were no intraventricular hemorrhages; 1 estradiol animal displayed ectactic vessels in the subarachnoid space., Conclusion: Brief postnatal estradiol administration to primates does not pose an increased risk of injury or impaired brain development., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Ibuprofen is an effective pharmacological intervention for closure of a patent ductus arteriosus (PDA) in preterm infants and is an alternative to surgical ligation; however, it is not certain whether ibuprofen treatment is associated with adverse effects on the brain. Therefore, this study examined neuropathological outcomes of ibuprofen therapy for a PDA. Fetal baboons were delivered at 125 d of gestation (dg; term ∼185 dg) by caesarean section, given surfactant, and ventilated for 14 d with positive pressure ventilation (PPV). Baboons were randomly allocated to receive either ibuprofen (PPV+ ibuprofen, n = 8) or no therapy (PPV, n = 5). Animals were killed on day 14 and brains assessed for cerebral growth, development, and neuropathology. Body and brain weights, the total volume of the brain, and the surface folding index (measure of brain growth) were not different (p > 0.05) between PPV+ ibuprofen-treated and PPV animals. There was no difference (p > 0.05) in the number of myelin basic protein-immunoreactive (IR) oligodendrocytes, glial fibrillary acid protein-IR astrocytes, or Iba1-IR macrophages/microglia in the forebrain. No overt cerebellar alterations were observed in either group. Ibuprofen treatment for PDA closure in the preterm baboon neonate is not associated with any increased risk of neuropathology or alterations to brain growth and development.

Intrauterine infection and inflammation have been linked to preterm birth and brain damage. We hypothesized that recombinant human erythropoietin (rhEPO) would ameliorate brain damage in anovine model of fetal inflammation. At 107 +/- 1 day of gestational age (DGA), chronically catheterized fetal sheep received on 3 consecutive days 1) an intravenous bolus dose of lipopolysaccharide ([LPS] approximately 0.9 microg/kg; n = 8); 2) an intravenous bolus dose of LPS, followed at 1 hour by 5,000 IU/kg of rhEPO (LPS + rhEPO, n = 8); or 3) rhEPO (n = 5). Untreated fetuses (n = 8) served as controls. Fetal physiological parameters were monitored, and fetal brains and optic nerves were histologically examined at 116 +/- 1 DGA. Exposure to LPS, but not to rhEPO alone or saline, resulted in fetal hypoxemia, hypotension (p < 0.05), brain damage, including white matter injury, and reductions in numbers of myelinating oligodendrocytes in the corticospinal tract and myelinated axons in the optic nerve (p < 0.05 for both). Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological effects of LPS but reduced brain injury and was beneficial to myelination in the corticospinal tract and the optic nerve. This is the first study in a long-gestation species to demonstrate the neuroprotective potential of rhEPO in reducing fetal brain and optic nerve injury after LPS exposure.

High-frequency oscillatory ventilation (HFOV) may improve pulmonary outcome in very preterm infants, but the effects on the brain are largely unknown. We hypothesized that early prolonged HFOV compared with low volume positive pressure ventilation (LV-PPV) would not increase the risk of delayed brain growth or injury in a primate model of neonatal chronic lung disease. Baboons were delivered at 127 +/- 1 d gestation (dg; term approximately 185 dg), ventilated for 22-29 d with either LV-PPV (n = 6) or HFOV (n = 5). Gestational controls were delivered at 153 dg (n = 4). Brains were assessed using quantitative histology. Body, brain, and cerebellar weights were lower in both groups of prematurely delivered animals compared with controls; the brain to body weight ratio was higher in HFOV compared with LV-PPV, and the surface folding index was lower in the LV-PPV compared with controls. In both ventilated groups compared with controls, there was an increase in astrocytes and microglia and a decrease in oligodendrocytes (p < 0.05) in the forebrain and a decrease in cerebellar granule cell proliferation (p < 0.01); there was no difference between ventilated groups. LV-PPV and HFOV ventilation in prematurely delivered animals is associated with decreased brain growth and an increase in subtle neuropathologies; HFOV may minimize adverse effects on brain growth.

The aim of this study was to determine whether inner retinal dysfunction in diabetic rats is correlated with structural and/or biochemical changes in the retina and optic nerve. Using the electroretinogram (ERG; -5.83 to 1.28 log cd.s.m(-2)) retinal function (photoreceptor, bipolar, amacrine and ganglion cell components) was measured in control (n=13; citrate buffer) and diabetic (n=13; streptozotocin, STZ, 50 mg kg(-1)) rats, 12 weeks following treatment. Retinae and optic nerves were analyzed for structural changes and retinae were assessed for alterations in growth factor/cytokine expression using quantitative real-time PCR. We found that phototransduction efficiency was reduced 12 weeks after STZ-induced diabetes (-30%), leading to reduced amplitude of ON-bipolar (-18%) and amacrine cell (-29%) dominated responses; ganglion cell dysfunction (-84%) was more profound. In the optic nerve, nerve fascicle area and myelin sheath thickness were reduced (p<0.05), whereas the ratio of blood vessels and connective tissue to total nerve cross-sectional area was increased (p<0.05) in diabetic compared to control rats. In the retina, connective tissue growth factor (CTGF), transforming growth factor beta, type 2 receptor (TGFbeta-r2) mRNA and platelet-derived growth factor B (PDGF-B) mRNA were increased (p<0.035). Reduced ganglion cell function was correlated with increased CTGF and TGFbeta-r2, but not PDGF-B mRNA. In summary, the ganglion cell component exhibited the greatest level of dysfunction within the ERG components examined after 12 weeks of STZ-induced diabetes; the level correlated with increased CTGF and TGFbeta-r2 mRNA, but not with gross morphological changes in the retina or optic nerve.

A patent ductus arteriosus (PDA) alters pulmonary mechanics and regional blood flow in the preterm infant. Its significance with respect to brain injury and brain development are unclear. We evaluated the effects of surgical ductal ligation on the preterm baboon brain. Baboons were delivered at 125 d of gestation (dg, term approximately 185 dg) and ventilated for 14 d (n = 12). The PDA was ligated 6 d after delivery (n = 7) or left untreated (n = 5). Animals were euthanized at 139 dg and brains compared histologically with gestational control fetuses (n = 7) at 140 dg. Brain and body weights were reduced (p < 0.05) in both groups of ventilated preterm animals; however, the brain to body weight ratio was increased (p < 0.01) in ligated, but not unligated newborns compared with gestational controls. No overt lesions were observed in either premature newborn group. Astrocyte density in the neocortex and hippocampus were greatest in the unligated newborns (p < 0.01). Myelination and oligodendrocytes were reduced (p < 0.05) in both premature newborn groups. The brain growth and development index was reduced, and the damage index was increased in prematurely delivered baboons. Surgical ligation of the PDA does not increase the incidence of brain injury and may be beneficial if the PDA is contributing to persistent pulmonary and hemodynamic instability.

Inhaled nitric oxide (iNO) enhances ventilation in very preterm infants, but the effects on the brain remain uncertain. We evaluated the impact of iNO on brain growth and cerebral injury in a premature baboon model. Baboons were delivered at 125 d of gestation (term 185 d of gestation) and ventilated for 14 d with either positive pressure ventilation (PPV) (n = 7) or PPV + iNO (n = 8). Brains were assessed histologically for parameters of development and injury. Compared with gestational controls (n = 7), brain and body weights were reduced but brain-to-body weight ratios were increased in all prematurely delivered (PD) animals; the surface folding index (SFI), was reduced in PPV but not PPV + iNO animals. Compared with controls, the brain damage index was increased (p < 0.05) in both cohorts of PD animals. There was no difference between ventilatory regimens, however, in 25% of animals with iNO therapy, there were organized hematomas in the subarachnoid space. Overall, iNO did not alter the extent of brain damage but did result in the presence of hematomas. These results do not confirm any protective or major injurious effect of nitric oxide therapy on the developing brain.

Purpose: Intrauterine infection has been linked to preterm delivery and neurologic injury. The purpose of this study was to investigate the effects of fetal inflammation induced by exposure to endotoxin on the structure and neurochemistry of the retina and optic nerve., Methods: The bacterial endotoxin, lipopolysaccharide (LPS), was administered to fetal sheep at approximately 0.65 of the approximately 147-day gestation period via repeated bolus doses (1 microg/kg per day) over 5 days, with fetal retinas and optic nerves assessed 10 days after the first LPS exposure., Results: In the retina, the total number of tyrosine hydroxylase immunoreactive (TH-IR), dopaminergic amacrine cells was reduced (P < 0.05) in LPS-exposed compared with control fetuses. There was no difference in the number of ChAT-, substance P-, or NADPH-d-positive amacrine cells. The total number of myelinated axons in the optic nerve was not different (P > 0.05) between groups; however, the myelin sheath was thinner (P < 0.05) in LPS-exposed fetuses., Conclusions: Prenatal exposure to repeated doses of endotoxin results in alterations to the retina and optic nerve with specific effects on dopaminergic neurons and myelination, respectively. These findings could have implications for visual function.

Background: The survival of prematurely born infants has greatly increased in recent decades because of advances in neonatal intensive care, which have included the advent of ventilatory therapies. However, there is limited knowledge as to the impact of these therapies on the developing brain. The purpose of this work was to evaluate the influence of randomized respiratory therapy with either early continuous positive airway pressure or delayed continuous positive airway pressure preceded by positive pressure ventilation on the extent of brain injury and altered development in a prematurely delivered primate model., Methods: Fetal baboons were delivered at 125 days of gestation (term: approximately 185 days of gestation) by cesarean section. Animals were maintained for 28 days postdelivery with either: early continuous positive airway pressure (commencing at 24 hours; n = 6) or delayed continuous positive airway pressure (positive pressure ventilation for 5 days followed by nCPAP; n = 5). Gestational controls (n = 4) were delivered at 153 days of gestation. At the completion of the study, animals were killed, the brains were assessed histologically for growth and development, and evidence of cerebral injury and indices for both parameters were formulated., Results: Brain and body weights were reduced in all of the nasal continuous positive airway pressure animals compared with controls; however, the brain/body weight ratio was increased in early continuous positive airway pressure animals. Within both nasal continuous positive airway pressure groups compared with controls, there was increased gliosis in the subcortical and deep white matter and cortex and a persistence of radial glia. Early continuous positive airway pressure was associated with less cerebral injury than delayed continuous positive airway pressure therapy. Neuropathologies were not observed in controls., Conclusions: Premature delivery, in the absence of potentiating factors, such as hypoxia or infection, is associated with a decrease in brain growth and the presence of subtle brain injury, which seems to be modified by respiratory therapies with early continuous positive airway pressure being associated with less overall cerebral injury.

Prenatal hypoxia affects neuronal survival and process outgrowth. Brain-derived neurotrophic factor, which influences neural growth, is decreased in these conditions. We tested whether addition of brain-derived neurotrophic factor enhances growth of neurons cultured from guinea pig fetuses (n=7) compromised by chronic placental insufficiency from 30-52 days gestation (term approximately 67 days). Cultures were prepared from the olfactory bulb, hippocampus and cerebellum. Compared with controls (n=7), chronic placental insufficiency resulted in reduced total neurite length in olfactory bulb cultures. Brain-derived neurotrophic factor treatment for 5 days increased the total olfactory neurite length and somal size and number of primary neurites in all cultures from both control and compromised animals. Thus, brain-derived neurotrophic factor can influence the growth of compromised fetal neurons supporting its therapeutic use following chronic placental insufficiency.

Purpose: Reduced birth weight is associated with an increased risk of visual impairments. This study was undertaken to determine whether prenatal exposure to a chronic compromise sufficient to cause fetal growth restriction (FGR) results in long-term alterations to the retina and optic nerve., Methods: FGR was induced by umbilicoplacental embolization (UPE) in two cohorts of pregnant ewes from (1) 120 days of gestation (dg) until 140 dg and (2) 120 dg until term ( approximately 147 dg). Control fetuses were not subjected to UPE. The structure and neurochemistry of the retina and number and structure of ganglion cell axons were assessed in near-term (140 dg) and adult animals (2.3 years)., Results: In near-term FGR fetuses compared with control fetuses there were significant reductions (P < 0.05) in the outer plexiform layer (OPL), the photoreceptor inner and outer segment layers, the inner nuclear layer (INL) in the central retina and the outer nuclear layer (ONL) in the peripheral retina, and the diameter of ganglion cell axons in the optic nerve, with a proportional reduction in the thickness of myelin sheaths. In FGR animals compared with the control at 2.3 years, there were significant reductions (P < 0.05) in the total thickness of the retina, the thickness of the photoreceptor outer segment layer and the INL and the number of tyrosine hydroxylase-immunoreactive (TH-IR) dopaminergic amacrine cells. Axonal diameter and myelin sheath thickness in the optic nerve were not different (P > 0.05) between groups., Conclusions: Chronic placental insufficiency in late gestation results in long-lasting effects on specific retinal components, including photoreceptor outer segments and TH-IR amacrine cells. Other alterations observed at term, including reductions in growth and myelination of optic nerve axons, do not persist, suggesting delayed rather than permanently compromised development. Alterations persisting into adulthood could affect visual function.

The aim of the present study was to establish the neurochemical profile of amacrine and horizontal cells during ontogeny in the guinea pig, a precocial species where significant retinal development occurs prenatally as opposed to altricial species where development largely occurs postnatally. The expression of neurochemical markers of horizontal cells and specific amacrine cell populations was investigated from 20 days of gestation (dg, term approximately 67 dg) to adulthood. Amacrine cell populations were identified immunohistochemically using antibodies to gamma-amino-butyric acid, cholineacetyltransferase, calbindin, calretinin, neuronal nitric oxide synthetase and tyrosine hydroxylase; horizontal cells were labelled with calbindin. All markers were present at 30 dg and had attained their mature (adult) laminar distribution and expression by 60 dg. Horizontal cells appeared in their final location at 30 dg with amacrine cell populations appearing in their final locations by 45 dg. Thus, in the guinea pig retina, the amacrine and horizontal cell populations investigated in this study are fully mature prior to birth.

Chronic placental insufficiency (CPI) has the potential to affect fetal brain development and to cause brain injury. Our aim was to determine the effects of exposure to CPI during late gestation on brain and retinal structure and brain neurotrophin expression 8 weeks after birth. Six fetal sheep were exposed to CPI, induced by umbilico-placental embolization, from 120 days of gestation until term (approximately 147 days) such that fetal arterial oxygen saturation (SaO2) was reduced by approximately 50%. Nine untreated animals served as controls. During CPI, fetal arterial PO2, SaO2, pH, and growth were reduced (p < 0.05); these animals remained small at 8 weeks after birth. Structural abnormalities were present in the brains and retinae of all CPI-exposed lambs. There was a reduction in retinal width and in the number of retinal tyrosine hydroxylase-immunoreactive dopaminergic amacrine cells (p < 0.05). In the dorsal hippocampus the combined width of strata oriens and pyramidale was significantly reduced (p < 0.05). In the cerebellum there was a significant reduction (p = 0.05) in cerebellar cross-sectional area, most notably in the inner granule cell layer, and a reduction (p < 0.05) in immunoreactivity for the cytoskeletal protein neurofilament-200 in the white matter. Gliosis was present in either the cerebral white matter or cerebellum in all animals and degeneration was seen around blood vessels in 4/6 umbilico-placental embolization animals. There were reductions in brain-derived neurotrophic factor immunoreactivity in the hippocampus (p < 0.05) and tyrosine kinase B immunoreactivity in the cerebellum (p < 0.05). This study shows that late gestational CPI affects morphology and neurotrophin expression of the postnatal brain. These alterations in the brain can apparently persist from fetal life or become established after birth; some changes that were present in the fetus at term did not persist into postnatal life.

Objective: Previous studies on the effects of umbilical cord occlusion (UCO) on the fetal brain have focused on short-term alterations, and in most cases have used only subjective techniques to evaluate brain injury. Our aim was to assess quantitatively the persistent consequences of UCO on the developing brain; we also examined the retina., Methods: We subjected fetal sheep to a single episode of UCO at 126 days of gestation (term approximately 147 days) to induce at least 10 minutes of isoelectric fetal electrocorticogram (ECoG)., Results: UCO resulted in fetal asphyxia and transient mild alterations in fetal mean arterial pressure (MAP). UCO did not result in significant injury to the developing brain or retina when assessed 15 days after the insult. There was no change in the endogenous expression of brain-derived neurotrophic factor (BDNF) protein in the hippocampus, nor was there a significant loss of CA1 hippocampal pyramidal cells. However, this insult did result in subtle neuropathologic alterations in the brain, including a reduction in the weight of the cerebral hemispheres, an increase in the areal density of cerebellar Purkinje cells, and enlarged perivascular spaces around blood vessels and inflammatory cells in the cerebral white matter. UCO did not affect the thickness of the central or peripheral retina or the numbers of retinal dopaminergic, cholinergic, and nitrergic amacrine cells., Conclusions: Thus, while 10 minutes of UCO did not result in overt injury to the fetal brain or retina, the observed changes in the fetal brain suggest altered growth of neural processes, which may contribute to neurologic deficits postnatally or to increased vulnerability of the brain to later insults during either the remainder of gestation or after birth.

Purpose: Very low birth weight (VLBW) and fetal growth restriction are associated with increased risks of long-term visual impairments, including alterations to contrast sensitivity, a parameter mediated in part by dopaminergic amacrine cells. This study was conducted to determine whether chronic placental insufficiency (CPI), sufficient to cause growth restriction, results in neurochemical alterations to retinal interneurons, specifically amacrine and horizontal cell populations near term., Methods: CPI was induced just before midgestation (term approximately 67 days of gestation, dg) in guinea pigs through unilateral ligation of the uterine artery. Growth-restricted (GR, n = 32) and control (n = 29) fetuses were euthanized at 60 dg and retinas prepared for analysis of amacrine cell populations by using antibodies to calbindin, calretinin, cholineacetyltransferase (ChAT), gamma-amino-butyric acid (GABA), dopamine beta-hydroxylase (D beta H), tyrosine hydroxylase (TH, dopaminergic), and NADPH-diaphorase histochemistry (nitrergic). Calbindin immunoreactivity (IR) was also used to identify horizontal cells. HPLC was used to assess concentrations of catecholamines and Western blot analysis to detect total TH levels., Results: In GR compared with control fetuses the total number of TH-IR amacrine (P < 0.02) and calbindin-IR horizontal (P < 0.05) cells was reduced; however, there were no differences in the number of the ChAT, calbindin, calretinin, GABAergic, or nitrergic amacrine cell populations. HPLC revealed a reduction in the concentration of dopamine (P < 0.05) and noradrenaline (P < 0.05), and Western blot analysis revealed a reduction in TH in the retinas of GR compared with control fetuses (P < 0.05)., Conclusions: CPI results in alterations to specific populations of retinal neurons. Such effects could contribute to visual impairments reported for VLBW children.

Our aim was to test the hypothesis that the fetal brainstem is relatively spared, compared to other brain regions, from hypoxia-induced damage. We have used established experimental models of acute and chronic intrauterine compromise in sheep to mimic conditions that can arise in human pregnancy. The acute insult was 12 h of placental insufficiency induced by restricted utero-placental blood flow at 90 days of gestation (term approximately 147 days). Five weeks after this insult (n=7 fetuses) there was no overt damage to the brainstem nor were there alterations to the blood vessel morphology, volume of the medulla or of medullary nuclei compared to controls (n=8). This regimen is known to have significant effects on the forebrain and cerebellum. The chronic insult was induced in five fetuses via embolisation of the umbilico-placental circulation from 120 to 140 days of gestation. An additional three fetuses were found to be spontaneously hypoxemic (SH) immediately after surgery. At 140 days, in brainstems of all chronically hypoxemic fetuses compared to controls (n=8), there was an increase (P<0.05) in the percentage of neuropil occupied by blood vessels and abnormal myelin in the most severely SH fetus but no other morphological or neurochemical alterations. This regimen is known to cause marked damage to the cerebral hemispheres and to a lesser extent to the cerebellum. We suggest that the absence of marked structural or neurochemical alterations in the brainstem is most likely due to the maintenance of oxygen delivery to the brainstem during fetal hypoxemia.

The aim of this study was to determine the effects of foetal growth restriction on the retina after birth. Foetal growth restriction (FGR) was induced via umbilico-placental embolization (UPE) in ewes from 120 days of pregnancy until term (term approximately 147 days); controls were not exposed to UPE. Lambs were delivered and raised until 2 years of age when retinas were collected and processed for structural and neurochemical analysis. The foetuses exposed to UPE were hypoxemic and at birth were growth restricted. In 2-year-old FGR sheep, the total thickness of the retina and the number of tyrosine hydroxylase immunoreactive dopaminergic amacrine cells were reduced compared to controls (P < 0.05). It is concluded that restricted foetal growth leads to long-term structural and neurochemical changes in the retina. Of particular interest are the alterations to dopaminergic amacrine cell numbers, as alterations in this population may affect contrast sensitivity and have implications for the alterations in vision observed in very low birthweight infants.

Very low birth weight and growth-restricted infants have an increased risk of auditory impairments. It is uncertain whether these impairments are related to adverse pre-, peri- or postnatal events. We aimed to determine whether a period of chronic placental insufficiency (CPI) in the guinea pig results in long-term alterations to auditory function. Near mid-gestation, CPI was induced via unilateral ligation of the uterine artery. At 8 weeks of age, auditory brainstem responses (ABRs) were recorded in response to unilateral acoustic stimulation in prenatally-compromised (PC, n=8) and control animals (n=8). Stimuli consisted of 100 micros clicks, presented at 33 pulses per second (pps) and tone pip stimuli at frequencies of 2, 4, 8, 16 and 32 kHz. To examine temporal response properties, click stimuli were also presented at rates of 66, 132 and 200 pps. Normal ABR waveforms were elicited by both click and tone pip stimuli in all animals. Moreover, there was no difference between control and PC animals in stimulus detection thresholds across the frequencies examined. Using high rate click stimuli, PC animals demonstrated a significant increase in both the latency of wave III (normalised to 33 pps) and the wave I-III inter-peak interval compared to the controls. We hypothesise that these functional changes reflect alterations in myelination of the auditory brainstem and/or changes in synaptic efficacy. The results suggest subtle deficits in neural conduction in the PC guinea pig at maturity, and may have implications for speech perception abilities of low birth weight or prenatally affected infants.

Purpose: To consider whether growth restriction secondary to chronic placental insufficiency results in postnatal deficits in retinal structure and function., Methods: Chronic placental insufficiency was induced just before midgestation in guinea pigs through unilateral ligation of the uterine artery. Eight weeks after birth, electroretinograms were recorded from prenatally compromised (PC, n = 6) and control (n = 15) animals. Data were collected for b-wave amplitude and implicit time, also the modeled receptoral (P3) response and oscillatory potentials were extracted. After electroretinography, retinas were prepared for structural analysis (PC, n = 6; control, n = 7). A separate cohort of PC (n = 8) and control (n = 9) animals underwent tyrosine hydroxylase immunoreactivity (TH-IR, dopaminergic neurons) and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry (neuronal nitric oxide synthase, nNOS)--these being markers of amacrine cell subpopulations., Results: Electroretinography revealed two PC guinea pigs with marked changes to saturated receptoral amplitude (Rm(P3)), sensitivity (log S) and postreceptoral waveforms. Grouped PC data revealed significantly reduced Rm(P3), whereas log S was not affected. The b-wave amplitudes were normal, but b-wave implicit times were delayed (P < 0.05) in PC animals. Amplitudes and peak times of oscillatory potentials were also significantly reduced and delayed (P < 0.05). Morphologic analysis revealed significant reductions in all cellular and plexiform (synaptic) layers in both the central (P < 0.05) and peripheral (P < 0.05) retina in PC animals. The outer retina, which contains the photoreceptors and the outer plexiform layer was particularly affected. The reduced growth of plexiform layers suggests a reduction in the growth of the neuropile in PC animals compared with control animals. The total number (P < 0.03) and density (P < 0.05) of TH-IR neurons was reduced, whereas the total number and density of nNOS-positive amacrine cells was not significantly different between PC and control animals., Conclusions: Chronic placental insufficiency results in morphologic and functional alterations to the retina. Electroretinogram deficits in PC animals indicated both inner and outer retinal anomalies. Such affects could contribute to the visual impairments reported in very-low-birth-weight children, some of whom are growth restricted.

It has been proposed that Sudden Infant Death Syndrome (SIDS) might occur as a consequence of a developmental deficit associated with the cardiorespiratory and arousal control centers located within the brainstem. In this study 1.1' dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate (DiI) was used to investigate the trajectories of the glossopharyngeal and vagus nerves which carry essential afferent and efferent fiber tracts associated with cardiac and respiratory control and of the hypoglossal nerve which innervates the tongue, in SIDS (n = 14) and control (n = 7) infants. The postnatal development of the trajectories of these nerves was examined in non-SIDS brains and comparisons were then made with age-matched SIDS brains. The mean profile area of hypoglossal and dorsal motor neurons were also assessed. In controls, no major alterations were observed in the trajectories of axon bundles with increasing age (7 wk to 2 yr) in each of the nerves investigated although axon bundles appeared to increase in thickness with age. In SIDS cases (2 wk to 44 wk), the trajectories of the cranial nerves were not different from those seen in age-matched control cases. The mean profile area of hypoglossal and dorsal motor neurons was not significantly different between control and SIDS infants. We conclude that the DiI tracing technique can be used successfully to trace the pathways of cranial nerves in human infant fixed-tissue. Furthermore, if functional differences exist between SIDS and non-SIDS brains in the control of respiration, circulation, or arousal they do not appear to be related to markedly reduced or aberrant projections of the glossopharyngeal, vagus, or hypoglossal nerves.