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Biomedical subjects

Carlos E Blanco

Publications and source records attributed to Carlos E Blanco.

At least 19 recordsLinked to original sources
PubMed2006

Ontogeny of chicken ductus arteriosus response to oxygen and vasoconstrictors.

The present study aimed to characterize the contractile reactivity of the chicken ductus arteriosus (DA) from the last stage of prenatal development and throughout the perinatal period. Isolated DA rings from 15-day, noninternally-pipped 19-day, and externally-pipped 21-day embryos were studied using myograph techniques. On embryonic day 15, the chicken DA did not respond to O(2) (0 to 21%), norepinephrine (NE), or phenylephrine (Phe) but contracted in response to high-K(+) solution, the inhibitor of voltage-gated channels 4-aminopyridine, U-46619, and endothelin (ET)-1. These responses increased with advancing incubation age. Contractile responses to O(2), NE, and Phe were present in the 19- and 21-day embryo. Oxygen-induced contraction was restricted to the pulmonary side of the DA and was augmented by the nitric oxide synthase inhibitor N(omega)-nitro-l-arginine methyl ester and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one and reduced by the peptidic ET(A) and ET(B)-receptor antagonist PD-142,893. Transmural electrical stimulation of nerves, the nonselective cyclooxygenase (COX) inhibitor indomethacin, the COX-1 inhibitor valeryl salicylate, the COX-2 inhibitor nimesulide, the inhibitor of ATP-sensitive K(+) channels glibenclamide, and the inhibitor of Ca(2+)-activated K(+) channels tetraethylammonium did not cause contraction of the DA rings at any age. We conclude that transition to ex ovo life is accompanied by dramatic changes in chicken DA reactivity. At 0.7 incubation, excitation-contraction and pharmacomechanical coupling for several contractile agonists are already present, whereas the constrictor effects of O(2) and cathecolamines appear later in development and are located in the pulmonary side of the DA.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2006

Prenatal stress reduces S100B in the neonatal rat hippocampus.

Prenatal stress has been shown to disturb neonatal rat brain development. The astroglial-specific neurotrophic factor S100B is known to play an important role in normal brain development. In the present study, we investigated the effects of prenatal stress on S100B concentrations in the hippocampus of 1-day-old Fischer 344 rats. Overall, prenatal stress resulted in a 25% reduction in hippocampal S100B content. Further, male hippocampal S100B content was negatively correlated with plasma corticosterone levels. Positive correlations were found between female S100B levels and fetal growth, and hippocampal brain-derived neurotrophic factor content. In conclusion, the observed reduction in neonatal hippocampal S100B levels, as a consequence of prenatal stress, may be involved in affecting postnatal brain development.

Analysis of Variance↗
PubMed2006

Cognition- and anxiety-related behavior, synaptophysin and MAP2 immunoreactivity in the adult rat treated with a single course of antenatal betamethasone.

We investigated the effects of a single course of antenatal betamethasone on cognition- and anxiety-related behavior and synaptophysin and microtubule-associated protein 2 (MAP2) immunoreactivity in the adult rat hippocampus. On d 20 of gestation, pregnant rats were injected with either 1) 170 microg/kg body weight of betamethasone ("clinically equivalent dose," equivalent to 12 mg twice, 24 h apart); 2) half this dose; or 3) vehicle. Cognition- and anxiety-related behavior of the offspring was analyzed at an age of 5 mo using the Morris water maze, object recognition task, and open field test. Subsequently, synaptophysin and MAP2 immunoreactivity were measured in the hippocampus. We report no detrimental effects of antenatal betamethasone on cognition- and anxiety-related behavior and synaptophysin immunoreactivity in the adult rat. On the other hand, MAP2 immunoreactivity was decreased by betamethasone in males, suggesting a permanent impairment in the hippocampus. Interestingly, the lower dose appears to have less influence in terms of growth restriction, known to be associated with an increased risk of disease in adulthood. Further research might elucidate whether the betamethasone effect on hippocampal neurons persists later in life and could affect the aging process increasing the risk for neuropathology of the adult.

Animals↗
PubMed2006

Lowering the dose of antenatal steroids: the effects of a single course of betamethasone on somatic growth and brain cell proliferation in the rat.

We investigated the effects of a single course of antenatal betamethasone on neonatal somatic and brain development. On day 20 of gestation, pregnant rats were injected with either with 170 microg kg(-1) body weight of betamethasone ("clinically-equivalent dose," equivalent to 12 mg twice, 24 hours apart) or half this dose or vehicle. Pups (8-11 animals per experimental group per timepoint per gender) were analyzed at 1 (P1), 2, and 21 days after birth. We report that betamethasone induced a significant dose-dependent decrease of somatic measurements in both genders. At P1 cell proliferation was affected by the "clinically equivalent dose" only in the subventricular zone in both genders and in the hippocampus in males. In summary, we show for the first time that a lower dose (equivalent to 6 mg) induces fewer and less severe effects on somatic growth, whereas it does not affect cell proliferation within the brain.

Animals↗
PubMed2005

A single course of antenatal betamethasone reduces neurotrophic factor S100B concentration in the hippocampus and serum in the neonatal rat.

The effects of a single course of antenatal betamethasone on S100B protein concentration were investigated in Fisher 344 rats. On day 20 of gestation, pregnant rats were injected twice 8 h apart with either (1) 170 microg kg(-1) body weight betamethasone ("clinically-equivalent dose", equivalent to 12 mg twice, 24 h apart in humans), (2) half of this dose (equivalent to 6 mg) or (3) vehicle. We report reference values for S100B protein in the serum and different brain regions in both genders at 1, 2, and 21 days after birth. Interestingly, S100B concentration showed a time-dependent and brain region-specific pattern of expression. At P1, S100B was higher in the serum of males compared to females. In addition, we show that both doses of betamethasone decreased S100B concentration in the serum of males at P1, whereas in the hippocampus, it was reduced by the clinically-equivalent dose only. This suggests that lowering the dose of antenatal betamethasone may be less detrimental for brain maturation and therefore we reiterate the need for clinical trials with a low dose regimen.

Animals↗
PubMed2005

Baroreceptor reflex sensitivity in human neonates: the effect of postmenstrual age.

We performed a cross-sectional study in human infants to determine if indices of R-R interval variability, systolic blood pressure (SBP) variability, and baroreceptor reflex sensitivity change with postmenstrual age (PMA: gestational age+postnatal age). The electrocardiogram, arterial SBP and respiration were recorded in clinically stable infants (PMA, 28-42 weeks) in the quiet sleep state in the first days after birth. (Cross-)spectral analyses of R-R interval series and SBP series were performed to calculate the power of low-frequency (LF, indicating baroreceptor reflex activity, 0.04-0.15 Hz) and high-frequency (HF, indicating parasympathetic activity, individualized between the p-10 and p-90 values of respiratory frequency) fluctuations, and transfer function phase and gain. The mean R-R interval, and LF and HF spectral powers of R-R interval series increased with PMA. The mean SBP increased with PMA, but not the LF and HF spectral powers of SBP series. In the LF range, cross-spectral analysis showed high coherence values (>0.5) with a consistent negative phase shift between R-R interval and SBP, indicating a approximately 3 s lag in R-R interval changes in relation to SBP. Baroreceptor reflex sensitivity, calculated from LF transfer gain, increased significantly with PMA, from 5 (preterm) to 15 ms mmHg-1 (term). Baroreceptor reflex sensitivity correlated significantly with the (LF and) HF spectral powers of R-R interval series, but not with the LF and HF spectral powers of SBP series. The principal conclusions are that baroreceptor reflex sensitivity and spectral power in R-R interval series increase in parallel with PMA, suggesting a progressive vagal maturation with PMA.

Baroreflex↗
PubMed2005

High sodium intake increases blood pressure and alters renal function in intrauterine growth-retarded rats.

A suboptimal fetal environment increases the risk to develop cardiovascular disease in the adult. We reported previously that intrauterine stress in response to reduced uteroplacental blood flow in the pregnant rat limits fetal growth and compromises renal development, leading to an altered renal function in the adult offspring. Here we tested the hypothesis that high dietary sodium intake in rats with impaired renal development attributable to intrauterine stress, results in increased blood pressure, altered renal function, and organ damage. In rats, intrauterine stress was induced by bilateral ligation of the uterine arteries at day 17 of pregnancy. At the age of 12 weeks, the offspring was given high-sodium drinking water (2% sodium chloride). At the age of 16 weeks, rats were instrumented for monitoring of blood pressure and renal function. After intrauterine stress, litter size and birth weight were reduced, whereas hematocrit at birth was increased. Renal blood flow, glomerular filtration rate, and the glomerular filtration fraction were increased significantly after intrauterine stress. High sodium intake did not change renal function and blood pressure in control animals. However, during high sodium intake in intrauterine stress offspring, renal blood flow, glomerular filtration rate, and the filtration fraction were decreased, and blood pressure was increased. In addition, these animals developed severe albuminuria, an important sign of renal dysfunction. Thus, a suboptimal fetal microenvironment, which impairs renal development, results in sodium-dependent hypertension and albuminuria.

Aging↗
PubMed2005

Cardiopulmonary effects of chronic administration of the NO synthase inhibitor L-NAME in the chick embryo.

BACKGROUND: Experimental observations in mammalian models suggest that endothelial nitric oxide (NO) synthase (NOS) content and activity are decreased in persistent pulmonary hypertension of the newborn. OBJECTIVES: To test the hypothesis that disruption of NO signaling in the developing chick embryo lung may contribute to pulmonary hypertension. METHODS: We analyzed pulmonary arterial reactivity and structure and heart morphology of 19-day chick embryos (incubation time 21 days) that received a daily injection of the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mug per gram egg) or vehicle from day 12 until day 18. RESULTS: Exposure to L-NAME did not affect embryonic survival or body mass of the embryos. The contractile responses to KCl, endothelin-1, the thromboxane A2 mimetic U46619, noradrenaline, and electrical-field stimulation were not affected by exposure to L-NAME. In contrast, in ovo L-NAME exposure reduced the sensitivity of pulmonary arteries to acetylcholine (pD2: 6.53 +/- 0.14 vs. 6.96 +/- 0.13; p < 0.05) and this effect was reversed by the NOS substrate L-arginine. Relaxations induced by sodium nitroprusside or forskolin were not altered by chronic L-NAME. Pulmonary vessel density was not different, but the percentage medial wall area of small pulmonary arteries (external diameter 10-50 microm) was slightly but significantly increased in the embryos exposed to L-NAME. In addition, hearts of L-NAME-exposed embryos showed an increase in right and left ventricular wall area. CONCLUSIONS: Chronic inhibition of NOS produced, in the chick embryo, impairment of endothelium-dependent relaxation, structural remodeling of the pulmonary vascular bed and biventricular cardiac enlargement.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2005

Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia.

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker N(G)-nitro-L-arginine methyl ester (L-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, L-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after L-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.

Animals↗
PubMed2005

Age-related differences in vasoconstrictor responses to isoprostanes in piglet pulmonary and mesenteric vascular smooth muscle.

Isoprostanes are prostaglandin (PG)-like compounds produced nonenzymatically by free radical-catalyzed peroxidation of arachidonic acid. Isoprostanes evoke potent vascular effects but their actions in the neonatal vasculature are poorly known. We aimed to study the effects of 8-iso-PGE(1), 8-iso-PGE(2), 8-iso-PGF(1alpha), 8-iso-PGF(1beta), 8-iso-PGF(2alpha), and 8-iso-PGF(2beta) in pulmonary arteries (PA), pulmonary veins (PV), and mesenteric arteries (MA) from newborn and 2-wk-old piglets. Isoprostanes produced concentration-dependent contractions of PA, PV, and MA (magnitudes up to 1.5- to 2-fold greater than the responses to 62.5 mM KCl) but they were markedly less potent vasoconstrictors than the thromboxane A(2) (TXA(2)) mimetic U46619. Neonatal PA were more sensitive to 8-iso-PGF(1alpha), 8-iso-PGF(1beta), and 8-iso-PGF(2beta) than 2-wk-old PA. Neonatal PV were more sensitive to 8-iso-PGE(2) and 8-iso-PGF(1alpha), and neonatal MA were more sensitive to 8-iso-PGE(2), 8-iso-PGF(1alpha), 8-iso-PGF(1beta), 8-iso-PGF(2alpha), and 8-iso-PGF(2beta) than the corresponding 2-wk-old vessels. The sensitivity to U46619 decreased with postnatal age in MA but did not change in PA and PV. The contractile responses to all the isoprostanes and to U46619 were reverted by the TXA(2) receptor (TP) antagonist SQ 29,548. Moreover, isoprostane-evoked contractions in 2-wk-old PA were reduced by inhibitors of tyrosine kinase (genistein) and Rho kinase (Y 27632 and hydroxyfasudil) but not by inhibitors of protein kinase C (chelerythrine), mitogen-activated protein kinase kinase (PD 98059) or p38-kinase (SB 203580). In conclusion, isoprostanes produced compound-, tissue-, and age-dependent constriction of neonatal porcine pulmonary and mesenteric vascular smooth muscle. Isoprostane-evoked PA vasoconstriction involved TP receptors and activation of tyrosine kinases and Rho kinases.

Age Factors↗
PubMed2004

Cardiovascular autonomic regulation in preterm infants: the effect of atropine.

To study cardiovascular autonomic control, we assessed the effect of atropine on heart rate (HR) and blood pressure (BP) variability in 12 preterm infants (range 26-32 wk) before intubation for respiratory insufficiency. Spectral power analysis of R-R interval and systolic BP (SBP) series were estimated in a low-frequency (LF; 0.04-0.15 Hz) and high-frequency (HF; 0.4-1.5 Hz) band and evaluated for a 10-min period before and a 10-min period after atropine sulfate (0.01 mg/kg). Baroreceptor reflex (BR) functioning was estimated using transfer function analysis at LF (coherence, gain, and phase). Atropine resulted in a significant 12% increase in steady-state HR (p < 0.01) and unchanged SBP. For R-R interval series, the total spectral power decreased 6-fold (p < 0.01), which was predominantly due to a reduction in the LF band (16-fold; p < 0.01). In contrast, we observed a significant increase (25%; p < 0.05) in total spectral power of SBP series partly as a result of an increase in HF power. The LF power of SBP series was not altered. The median LF transfer gain (BR sensitivity) between SBP and R-R interval decreased from 4.2 to 1.4 ms/mm Hg (p < 0.01) after atropine. The LF phase relationship (BP leads R-R interval fluctuations by approximately 4 s) was not changed after atropine. In conclusion, even in preterm infants in distress, atropine modulates HR and BP variability, suggesting that BR-mediated parasympathetic control of heart rate is of significance for cardiovascular control at that age.

Atropine↗
PubMed2004

Chronic in ovo hypoxia decreases pulmonary arterial contractile reactivity and induces biventricular cardiac enlargement in the chicken embryo.

Although chronic prenatal hypoxia is considered a major cause of persistent pulmonary hypertension of the newborn, experimental studies have failed to consistently find pulmonary hypertensive changes after chronic intrauterine hypoxia. We hypothesized that chronic prenatal hypoxia induces changes in the pulmonary vasculature of the chicken embryo. We analyzed pulmonary arterial reactivity and structure and heart morphology of chicken embryos maintained from days 6 to 19 of the 21-day incubation period under normoxic (21% O(2)) or hypoxic (15% O(2)) conditions. Hypoxia increased mortality (0.46 vs. 0.14; P < 0.01) and reduced the body mass of the surviving 19-day embryos (22.4 +/- 0.5 vs. 26.6 +/- 0.7 g; P < 0.01). A decrease in the response of the pulmonary artery to KCl was observed in the 19-day hypoxic embryos. The contractile responses to endothelin-1, the thromboxane A(2) mimetic U-46619, norepinephrine, and electrical-field stimulation were also reduced in a proportion similar to that observed for KCl-induced contractions. In contrast, no hypoxia-induced decrease of response to vasoconstrictors was observed in externally pipped 21-day embryos (incubated under normoxia for the last 2 days). Relaxations induced by ACh, sodium nitroprusside, or forskolin were unaffected by chronic hypoxia in the pulmonary artery, but femoral artery segments of 19-day hypoxic embryos were significantly less sensitive to ACh than arteries of control embryos [pD(2) (= -log EC(50)): 6.51 +/- 0.1 vs. 7.05 +/- 0.1, P < 0.01]. Pulmonary vessel density, percent wall area, and periarterial sympathetic nerve density were not different between control and hypoxic embryos. In contrast, hypoxic hearts showed an increase in right and left ventricular wall area and thickness. We conclude that, in the chicken embryo, chronic moderate hypoxia during incubation transiently reduced pulmonary arterial contractile reactivity, impaired endothelium-dependent relaxation of femoral but not pulmonary arteries, and induced biventricular cardiac hypertrophy.

Animals↗
PubMed2004

Reduced uteroplacental blood flow alters renal arterial reactivity and glomerular properties in the rat offspring.

Fetal malnutrition and hypoxia may modify organ system maturation and result in cardiovascular diseases in the adult. We tested whether intrauterine stress (IUS) leads to persistent alterations of renal biology. In rats, intrauterine stress was induced by ligation of the uterine arteries at day 17 of pregnancy. Renal arteries of the 21-day-old male offspring were isolated to study pharmacological reactivity. Kidneys were dissected to analyze renal structure and beta-adrenoceptor expression. At 21 days of age, half of the animals underwent unilateral left nephrectomy. At the age of 12 weeks, rats were instrumented for blood pressure monitoring, blood sampling, and renal function measurements. After IUS, litter size and birth weight were reduced, whereas the hematocrit was increased. Renal arterial responses to beta-adrenergic stimulation and sensitivity to adenylyl cyclase activation were increased, along with the renal expression of beta2-adrenoceptors. At 21 days and at 6 months of age, the number and density of the glomeruli were reduced, whereas their size was increased. The filtration fraction and urinary albumin concentration were increased 12 weeks after intrauterine stress. In control rats, removal of the left kidney at 21 days of age did not affect kidney function and blood pressure. However, after IUS, the remaining right kidney failed to compensate for the loss of the left kidney, and blood pressure was increased. In conclusion, prenatal stress transiently modifies renal arterial reactivity and results in long-lasting adverse effects on renal structure and function and on renal compensatory mechanisms.

Adaptation, Physiological↗
PubMed2003

Noninvasive assessment of blood pressure variability in preterm infants.

The feasibility of measuring blood pressure (BP) variability by a noninvasive beat-to-beat finger arterial BP device (Finapres) was assessed in preterm infants. By application of the finger cuff around the infant's wrist, time and frequency domain (spectral power) analysis of noninvasive beat-to-beat BP signals were compared with intra-arterial measurements. A fast Fourier Transform was used to compute the spectral power density from 128-s periods. The low-frequency band (LF; 0.04-0.15 Hz) is partly associated with baroreflex activity. The high-frequency band (HF; 0.4-1.5 Hz) is associated with respiratory activity. In eight subjects above 1000 g, reliable signals could be obtained. We observed a high correlation between noninvasive and intra-arterial beat-to-beat systolic BP values (mean r value +/- SD, 0.87 +/- 0.11), with a gain close to 1 (mean gain +/- SD, 1.0 +/- 0.4 mm Hg/mm Hg). Finapres estimated beat-to-beat systolic BP changes more accurately than diastolic values. We found a very high amount of linear coupling, expressed as coherence function, between the power spectra of noninvasive and intra-arterial systolic BP measurements. For systolic BP, the (pooled) group mean +/- SEM coherence values were 0.93 +/- 0.00 and 0.91 +/- 0.01 for LF and HF fluctuations, respectively (NS). The wrist method of Finapres in neonates has limited value in estimating absolute BP but is useful in a clinical research situation, where identification of beat-to-beat changes in systolic BP is more important. Finapres provides a noninvasive tool for investigating autonomic cardiovascular regulation (baroreflex sensitivity, spectral analysis of BP fluctuations) in neonates.

Baroreflex↗
PubMed2003

A single course of prenatal betamethasone in the rat alters postnatal brain cell proliferation but not apoptosis.

The aim of this study was to determine the effects of a clinically relevant single course of prenatal betamethasone in the rat on growth parameters with particular reference to brain cell proliferation and apoptosis. We report that administration of 170 microg kg-1 betamethasone twice within 4 h to E20 pregnant rats conveys moderate somatic growth retardation. Further, using a measure of brain cell proliferation independent of blood-brain barrier (BBB) permeability, we demonstrate for the first time that betamethasone is chronically anti-proliferative to brain cells without inducing caspase-3-mediated apoptosis. More importantly we show that there is a significant and sexually divergent rebound of neural proliferation which occurs earlier in males than in females and continues until at least 21 days of postnatal life. BBB permeability to [3H]thymidine was significantly increased by steroid treatment re-iterating the fact that tracer studies not correcting for BBB permeability, such as bromodeoxyuridine (BrdU), may be questionable in this type of study. Further, prenatal steroid treatment did not alter postnatal corticosterone levels. In summary we show that prenatal betamethasone conveys significant and long-lasting side effects and that its human clinical application in preterm labour needs more careful consideration as compared to the relative ease with which it is prescribed today.

Animals↗
PubMed2003

Role of superoxide anion on basal and stimulated nitric oxide activity in neonatal piglet pulmonary vessels.

The superoxide anion (O2*-) appears to be an important modulator of nitric oxide bioavailability. Enzymatic scavenging of O2*- is carried out by superoxide dismutase (SOD). The present study was designed to characterize the developmental changes on pulmonary vascular reactivity induced by 1) exogenous Cu/Zn SOD, 2) several putative SOD mimetics, and 3) endogenous SOD inhibition. We also analyzed age-related changes on pulmonary SOD activity and vascular O2*- levels. SOD (1-300 U/mL) produced endothelium-dependent relaxation of U46619-contracted intrapulmonary arteries (fourth branch) and veins from 12- to 24-h-old and 2-wk-old piglets. SOD-induced relaxation was greater in pulmonary arteries and was abolished by the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester. SOD induced a greater pulmonary artery relaxation in the 2-wk-old than in the 12- to 24-h-old piglet. SOD (100 U/mL) did not modify acetylcholine-induced relaxation in pulmonary arteries. In contrast, endogenous SOD inhibition by diethyldithiocarbamate (3 mM) impaired acetylcholine-induced relaxation in pulmonary arteries from newborn but not from 2-wk-old piglets. Total SOD activity in lung tissue did not change with postnatal age. With the use of dihydroethidium, an oxidant-sensitive fluorescent probe, we did not find significant age- or vessel-related differences in O2*- presence. From the putative SOD mimetics tested, only the metal salts MnCl2 and CuSO4 reproduced the vascular effects of SOD. In summary, SOD produces endothelium-dependent pulmonary vascular relaxation by protecting nitric oxide from destruction by O2*-. This effect was less marked in newborns than in 2-wk-old piglets. In contrast, pulmonary arteries from newborn piglets are more sensitive to the inhibition of endogenous SOD.

Acetylcholine↗
PubMed2003

A delayed increase in hippocampal proliferation following global asphyxia in the neonatal rat.

Adult neurogenesis has been shown to be upregulated following a wide variety of brain injury paradigms. During the first weeks of postnatal life there is around 50 fold more neurogenesis occurring than in the adult CNS, yet little is known regarding the effect of neonatal brain injury on this developmental proliferation. We have investigated the effect of a global perinatal birth asphyxia on postnatal proliferation at 2, 5, 8, 11, 15, 21 and 28 days after birth (injury) using a 3H-thymidine tracer study. We found a specific upregulation of proliferation at 5 days after the injury within the injured hippocampus only, with an associated increase in hippocampal mass and without any changes in GFAP content at any timepoint. Perinatal asphyxia did not alter proliferation within the cerebellum, sub ventricular zone, olfactory bulb, cervical or thoracic spinal cord. Similarly, no changes in corticosterone levels were induced by the injury. Since there were no changes in GFAP content we hypothesize that this increased proliferation is likely neurogenetic, similar to what is seen in the adult brain following injury. Further we show that the dramatic increase in corticosterone at the end of the stress hyporesponsive period is not responsible for the equally dramatic decrease in postnatal proliferation within the CNS.

Animals↗