The carbon footprint of the operating room related to infection prevention measures: a scoping review.

BACKGROUND: Infection prevention measures are widely used in operating rooms (ORs). However, the extent to which they are at odds with ambitions to reduce the health sector's carbon footprint remains unclear. AIM: To synthesize the evidence base for the carbon footprint of commonly used infection prevention measures in the OR, namely medical devices and instruments, surgical attire and air treatment systems. METHODS: A scoping review of the international scientific literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search was performed in PubMed and Google Scholar. Articles published between 2010 and June 2021 on infection prevention measures, their impact on the health sector's carbon footprint, and risk for surgical site infections (SSIs) were included. FINDINGS: Although hospitals strive to reduce their carbon footprint, many infection prevention measures result in increased emissions. Evidence suggests that the use of disposable items instead of reusable items generally increases the carbon footprint, depending on sources of electricity. Controversy exists regarding the correlation between air treatment systems, contamination and the incidence of SSIs. The literature indicates that new air treatment systems consume more energy and do not necessarily reduce SSIs compared with conventional systems. CONCLUSION: Infection prevention measures in ORs can be at odds with sustainability. The use of new air treatment systems and disposable items generally leads to significant greenhouse gas emissions, and does not necessarily reduce the incidence of SSIs. Alternative infection prevention measures with less environmental impact are available. Implementation could be facilitated by embracing environmental impact as an additional dimension of quality of care, which should change current risk-based approaches for the prevention of SSIs.

A life cycle assessment of reprocessing face masks during the Covid-19 pandemic.

The Covid-19 pandemic led to threatening shortages in healthcare of medical products such as face masks. Due to this major impact on our healthcare society an initiative was conducted between March and July 2020 for reprocessing of face masks from 19 different hospitals. This exceptional opportunity was used to study the costs impact and the carbon footprint of reprocessed face masks relative to new disposable face masks. The aim of this study is to conduct a Life Cycle Assessment (LCA) to assess and compare the climate change impact of disposed versus reprocessed face masks. In total 18.166 high quality medical FFP2 face masks were reprocessed through steam sterilization between March and July 2020. Greenhouse gas emissions during production, transport, sterilization and end-of-life processes were assessed. The background life cycle inventory data were retrieved from the ecoinvent database. The life cycle impact assessment method ReCiPe was used to translate emissions into climate change impact. The cost analysis is based on actual sterilization as well as associated costs compared to the prices of new disposable face masks. A Monte Carlo sampling was used to propagate the uncertainty of different inputs to the LCA results. The carbon footprint appears to be 58% lower for face masks which were reused for five times compared to new face masks which were used for one time only. The sensitivity analysis indicated that the loading capacity of the autoclave and rejection rate of face masks has a large influence on the carbon footprint. The estimated cost price of a reprocessed mask was €1.40 against €1.55. The Life Cycle Assessment demonstrates that reprocessed FFP2 face masks from a circular economy perspective have a lower climate change impact on the carbon footprint than new face masks. For policymakers it is important to realize that the carbon footprint of medical products such as face masks may be reduced by means of circular economy strategies. This study demonstrated a lower climate change impact and lower costs when reprocessing and reusing disposable face masks for five times. Therefore, this study may serve as an inspiration for investigating reprocessing of other medical products that may become scarce. Finally, this study advocates that circular design engineering principles should be taken into account when designing medical devices. This will lead to more sustainable products that have a lower carbon footprint and may be manufactured at lower costs.

[Steps for reducing the carbon footprint of the operating room]. / Manieren om de CO2-voetafdruk van de OK te verlagen.

The healthcare sector contributes significantly to global warming due to carbon emissions; this sector is, therefore, partially responsible for the negative effects of climate change on public health. Carbon emissions by the healthcare sector amount to 7% of the total carbon footprint of the Netherlands. It is anticipated that measures to reduce carbon emissions in the operating room (OR) can make an important contribution to reducing carbonemissions in the hospital as a whole. The most important elements contributing to the carbon footprint of the OR are: energy consumption for heating, ventilation and air conditioning (HVAC); the emission of inhalation anaesthetics; the purchase of materials and equipment; and waste production. Direct carbon emissions by the OR can be reduced through the use of sustainable energy and setback of the HVAC outside office hours. Anaesthetists can dramatically reduce the carbon footprint of the OR by choosing for intravenous anaesthetics instead of inhalation anaesthetics. Indirect carbon emissions and waste production by the OR can be reduced through circular procurement, choosing reusable over disposable products and recycling.

Sevoflurane based anaesthesia does not affect already impaired cerebral autoregulation in patients with type 2 diabetes mellitus.

BACKGROUND: The baroreflex regulates arterial blood pressure (BP). During periods when blood pressure changes, cerebral blood flow (CBF) is kept constant by cerebral autoregulation (CA). In patients with diabetes mellitus (DM), low baroreflex sensitivity (BRS) is associated with impaired CA. As sevoflurane-based anaesthesia obliterates BRS, we hypothesised that this could aggravate the already impaired CA in patients with DM resulting in a 'double-hit' on cerebral perfusion leading to increased fluctuations in blood pressure and cerebral perfusion. METHODS: On the day before surgery, we measured CBF velocity (CBFV), heart rate, and BP to determine BRS and CA efficacy (CBFVmean-to-BPmean-phase lead) in 25 patients with DM and in 14 controls. During the operation, BRS and CA efficacy were determined during sevoflurane-based anaesthesia. Patients with DM were divided into a group with high BRS (DMBRS↑) and a group with low BRS (DMBRS↓). Values presented are median (inter-quartile range). RESULTS: Preoperative vs intraoperative BRS was 6.2 (4.5-8.5) vs 1.9 (1.1-2.5, P<0.001) ms mm Hg-1 for controls, 5.8 (4.9-7.6) vs 2.7 (1.5-3.9, P<0.001) ms mm Hg-1 for patients with DMBRS↑, and 1.9 (1.5-2.8) vs 1.1 (0.6-2.5, P=0.31) ms mm Hg-1 for patients with DMBRS↓. Preoperative vs intraoperative CA efficacy was 43° (38-46) vs 43° (38-51, P=0.30), 44° (36-49) vs 41° (32-49, P=0.52), and 34° (28-40) vs 30° (27-38, P=0.64) for controls, DMBRS↑, and DMBRS↓ patients, respectively. CONCLUSIONS: In diabetic patients with low preoperative BRS, preoperative CA efficacy was also impaired. In controls and diabetic patients, CA was unaffected by sevoflurane-based anaesthesia. We therefore conclude that sevoflurane-based anaesthesia does not contribute to a 'double-hit' phenomenon on cerebral perfusion. CLINICAL TRIAL REGISTRATION: NCT 03071432.

Novel method for intraoperative assessment of cerebral autoregulation by paced breathing.

Background: Cerebral autoregulation (CA) is the mechanism that maintains constancy of cerebral blood flow (CBF) despite variations in blood pressure (BP). Patients with attenuated CA have been shown to have an increased incidence of peri-operative stroke. Studies of CA in anaesthetized subjects are rare, because a simple and non-invasive method to quantify the integrity of CA is not available. In this study, we set out to improve non-invasive quantification of CA during surgery. For this purpose, we introduce a novel method to amplify spontaneous BP fluctuations during surgery by imposing mechanical positive pressure ventilation at three different frequencies and quantify CA from the resulting BP oscillations. Methods: Fourteen patients undergoing sevoflurane anaesthesia were included in the study. Continuous non-invasive BP and transcranial Doppler-derived CBF velocity (CBF V ) were obtained before surgery during 3 min of paced breathing at 6, 10, and 15 bpm and during surgery from mechanical positive pressure ventilation at identical frequencies. Data were analysed using frequency domain analysis to obtain CBF V -to-BP phase lead as a continuous measure of CA efficacy. Group averages were calculated. Values are means ( sd ), and P <0.05 was used to indicate statistical significance. Results: Preoperative vs intraoperative CBF V -to-BP phase lead was 43 (9) vs 45 (8)°, 25 (8) vs 24 (10)°, and 4 (6) vs -2 (12)° during 6, 10, and 15 bpm, respectively (all P =NS). Conclusions: During surgery, cerebral autoregulation indices were similar to values determined before surgery. This indicates that CA can be quantified reliably and non-invasively using this novel method and confirms earlier evidence that CA is unaffected by sevoflurane anaesthesia. Clinical trial registration: NCT03071432.

Cerebral oxygenation during changes in vascular resistance and flow in patients on cardiopulmonary bypass - a physiological proof of concept study.

Despite a rise in blood pressure, cerebral oxygenation decreases following phenylephrine administration, and we hypothesised that phenylephrine reduces cerebral oxygenation by activating cerebral α1 receptors. We studied patients on cardiopulmonary bypass during constant flow. Phenylephrine raised mean arterial pressure (α1 -mediated) from mean (SD) 69 (8) mmHg to 79 (8) mmHg; p = 0.001, and vasopressin raised mean arterial pressure (V1 mediated) from 69 (8) mmHg to 83 (6) mmHg; p = 0.001. Both drugs elicited a comparable decrease in cerebral oxygenation from 61 (7)% to 60 (7)%; p = 0.023 and 61 (8)% to 59 (8)%; p = 0.022, respectively. This implies that after phenylephrine or vasopressin administration, cerebral oxygenation declines as a result of cerebral vasoconstriction, due to either both cerebral α1 and V1 receptors being equipotentially activated or to an intrinsic myogenic mechanism of cerebral vasculature in reaction to blood pressure elevation.

[Effects on health of the Chernobyl accident: 30 years on]. / Gesundheitliche Folgen des Unfalls von Tschernobyl - 30 Jahre danach.

This paper reflects the current state of research into the short- and long-term effects on health in the former Soviet Union and Europe of the nuclear accident in Chernobyl. It discusses the latest results of epidemiological studies and presents future research perspectives.

BpiB05, a novel metagenome-derived hydrolase acting on N-acylhomoserine lactones.

The N-acyl-homoserine lactones (N-AHLs) play an important role in bacterial cell-cell signaling. Up to date, however, only a few different experimentally proven classes of N-AHL ring-cleaving enzymes are known. Here we report on the isolation and biochemical characterization of a novel hydrolase derived from the soil metagenome and acting on N-AHLs. The identified protein designated BpiB05 is weakly similar to hypothetical proteins from Bacteroides fragilis, the draft genomes of two Burkholderia species as well as a marine metagenomic ORF but is otherwise not similar to any known protein. BpiB05 was overexpressed in Escherichia coli as a 10× His-tagged fusion protein. The recombinant protein revealed a molecular weight of about 70kDa and was tested for its quorum quenching (QQ) activities using a lacZ-bioassay. Additional HPLC-MS analyses confirmed the lactonolytic activity of the purified protein in the presence of Ca²âº. Further tests suggested that BpiB05 strongly reduces motility in Pseudomonas aeruginosa, pyocyanin synthesis and biofilm formation in this microbe. Because BpiB05 is not distantly related to any of the currently known hydrolases it forms probably a novel group within the growing number of proteins acting on N-AHLs.

Heterogeneity of hippocampal GABA(A) receptors: regulation by corticosterone.

Chronic stressors produce changes in hippocampal neurochemistry, neuronal morphology, and hippocampal-dependent learning and memory processes. In rats, stress-induced changes in CA3 apical dendritic structure are mediated by corticosterone (CORT) acting, in part, on excitatory amino acid neurotransmission. CORT also alters GABA-mediated inhibitory neurotransmission, so the GABA(A) receptor system may also contribute to dendritic remodeling and other stress-related changes in hippocampal function. A previous study indicated that chronic CORT treatment produces complex changes in GABA(A) receptor subunit mRNA levels, so we hypothesized that CORT alters the pharmacological properties of hippocampal GABA(A) receptors. To test this, adult male rats were treated with CORT or vehicle pellets for 10 d, after which we quantified [(35)S]t-butylbicyclophosphorothionate ([(35)S]TBPS) and [(3)H]flunitrazepam binding to GABA(A) receptors using in vitro receptor autoradiography. Pharmacological properties of receptors were assessed by examining the allosteric regulation of binding at both sites by GABA and 5alpha-pregnane-3alpha,21-diol-20-one (THDOC), an endogenous anxiolytic steroid. We found striking regional differences in the modulation of [(35)S]TBPS binding, particularly between strata radiatum and strata oriens, suggesting a functional heterogeneity among hippocampal GABA(A) receptors even within the apical versus basal dendrites of pyramidal neurons. Furthermore, we found that CORT treatment decreased the negative modulation of hippocampal [(35)S]TBPS binding by both GABA and THDOC and increased the enhancement of [(3)H]flunitrazepam binding by GABA and THDOC in the dentate gyrus. Together, these data suggest that prolonged exposure to stress levels of corticosteroids may alter hippocampal inhibitory tone by regulating the pharmacological properties of GABA(A) receptors in discrete dendritic subfields.

Inhibition of dendritic spine induction on hippocampal CA1 pyramidal neurons by a nonsteroidal estrogen antagonist in female rats.

Estrogens regulate the formation of excitatory synaptic connections in the hippocampus of female rats. Because the adult hippocampus has a very low concentration of intracellular estrogen receptors, it is unclear whether a conventional genomic mechanism is involved. Nonsteroidal estrogen antagonists are useful tools to study estrogen action because they can provide pharmacological data in favor of a particular pathway of estrogen action and evidence against other pathways. To investigate the role of intracellular estrogen receptors in the estrogen induction of synapse formation, we took advantage of previous studies in which we had shown that an estrogen antagonist, CI-628, enters the brain and blocks estrogen induction of progestin receptors to study whether the same antagonist would either mimic or block effects of estradiol to induce excitatory spine synapses. Using silver impregnation of neurons by the single section Golgi technique and morphometric analysis, we found that CI-628 effectively prevented estrogen induction of spines on CA1 pyramidal neurons, without having any agonist effects of its own. This result is consistent with an action of estradiol via intracellular estrogen receptors that are known to be expressed by interneurons within the hippocampus.

Clinically relevant basic science studies of gender differences and sex hormone effects.

Ovarian steroids produce a variety of effects on the brain, influencing diverse nonreproductive processes such as cognitive function, motor activity, seizure susceptibility, and pain sensitivity, as well as pathological processes such as Parkinson's disease and Alzheimer's disease. Studies of ovarian hormone effects on animal brains have revealed a wide array of neurochemical and structural effects of ovarian steroids, which are reviewed in this article. These studies provide a foundation for understanding hormone effects on mood, behavior, and cognition in the menstrual cycle, during reproductive transitions and in depressive illness.

Differential colocalization of estrogen receptor beta (ERbeta) with oxytocin and vasopressin in the paraventricular and supraoptic nuclei of the female rat brain: an immunocytochemical study.

Evidence exists for the localization of the newly identified estrogen receptor beta (ERbeta) within the rat paraventricular nucleus (PVN) and supraoptic nucleus (SON), regions which lack ERalpha. Presently, we investigate whether ERbeta-like-immunoreactivity (-ir) is found within cells of several major neuropeptide systems of these regions. Young adult Sprague-Dawley rats were ovariectomized (OVX), and 1 week later half of the animals received estradiol-17beta (E). Dual-label immunocytochemistry was performed on adjacent sections by using an ERbeta antibody, followed by an antibody to either oxytocin (OT), arginine-vasopressin (AVP), or corticotropin releasing hormone. Nuclear ERbeta-ir was identified within SON and retrochiasmatic SON, and in specific PVN subnuclei: medial parvicellular part, ventral and dorsal zones, dorsal and lateral parvicellular parts, and in the posterior magnocellular part, medial and lateral zones. However, the ERbeta-ir within magnocellular areas was noticeably less intense. OT-/ERbeta-ir colocalization was confirmed in neurons of the parvicellular subnuclei, in both OVX and OVX+E brains ( approximately 50% of OT and 25% of ERbeta-labeled cells between bregma -1.78 and -2.00). In contrast, few PVN parvicellular neurons contained both AVP- and ERbeta-ir. As well, very little overlap was observed in the distribution of cells containing corticotropin releasing hormone- or ERbeta-ir. In the SON, most nuclear ERbeta-ir colocalized with AVP-ir, whereas few OT-/ERbeta-ir dual-labeled cells were observed. These findings suggest that estrogen can directly modulate specific OT and AVP systems through an ERbeta-mediated mechanism, in a tissue-specific manner.

Immunocytochemical localization of nuclear estrogen receptors and progestin receptors within the rat dorsal raphe nucleus.

Estradiol and progesterone modulate central serotonergic activity; however, the mechanism(s) of action remain unclear. Recently, estradiol-induced progestin receptors (PRs) have been localized within the majority of serotonin (5-HT) neurons in the female macaque dorsal raphe nucleus (DRN; Bethea [1994] Neuroendocrinology 60:50-61). In the present study, we investigated whether estrogen receptors (ERs) and/or PRs exist within 5-HT and/or non-5-HT cells in the female and male rat DRN and whether estradiol treatment alters the expression of these receptors. Young adult female and male Sprague-Dawley rats were gonadectomized, and 1 week later, half of the animals received a subcutaneous Silastic implant of estradiol-17beta. Animals were transcardially perfused 2 days later with acrolein and paraformaldehyde, and sequential dual-label immunocytochemistry was performed on adjacent sections by using either a PR antibody or an ERalpha antibody. This was followed by an antibody to either the 5-HT-synthesizing enzyme, tryptophan hydroxylase (TPH), or to the astrocytic marker, glial fibrillary acidic protein (GFAP). Cells containing immunoreactivity (ir) for nuclear ERs or PRs were identified within the rat DRN in a region-specific distribution in both sexes. No colocalization of nuclear ER-ir or PR-ir with cytoplasmic TPH-ir or GFAP-ir was observed in either sex or treatment, indicating that the steroid target cells are neither 5-HT neurons nor astrocytes. Females were found to have approximately 30% more PR-labeled cells compared with males throughout the DRN (P < 0.05), but no sex difference was detected in the number of neurons demonstrating ER-ir. In both sexes, 2 days of estradiol exposure decreased the number of cells with ER-ir, whereas it greatly increased the number of cells containing PR-ir in several DRN regions (P < 0.005). Collectively, these findings demonstrate the existence of nonserotonergic cells that contain nuclear ERs or PRs within the female and male rat DRN, including estradiol-inducible PRs. These findings point to a species difference in ovarian steroid regulation of 5-HT activity between the macaque and the rat, perhaps transsynaptically via local neurons in the rat brain.

Distribution and hormone regulation of estrogen receptor immunoreactive cells in the hippocampus of male and female rats.

Estrogen regulates the synaptic plasticity and physiology of the hippocampus as well as learning behaviors that are mediated by the hippocampus. The density of dendritic spines and synapses, the number of N-methyl-D-aspartate (NMDA) binding sites, the levels of NMDA receptor subunit NR1 protein, muscimol binding to the gamma-amino butyric acid (GABA)A receptor, and levels of glutamic acid decarboxylase message in the CA1 region of the hippocampus are altered with estrogen treatment. In addition, some of these parameters exhibit sex differences in their response to estrogen treatment. To establish that estrogen can have a direct effect on the hippocampus and to determine whether or not sex differences in estrogen responsiveness are due to sex differences in estrogen receptor (ER) levels, we used immunocytochemistry with the AS409 antibody to map the location of ER-immunoreactive (ER-ir) cells in the hippocampus of male and female rats. We found that (1) the ERs appear to be in interneurons rather than pyramidal or granule cell neurons, (2) ER-ir cells are located in greatest concentration in the hilus of the dentate gyrus and the stratum radiatum of the CA1 region, (3) the density of ER-ir cells exhibits a rostral to caudal gradient in the hilus and the CA1 regions, (4) there are no sex differences in either the number or immunostaining intensity of ER-ir cells in the hippocampus, (5) the ER levels are down-regulated by estrogen in both male and female rats, and (6) the mean intensity of staining for the ER-ir cells in the hippocampus is about 25% of that in the ER-ir cells of the hypothalamus. From this, we can conclude that estrogen can have a direct effect on hippocampal neurons and that any sex differences in estrogen responsiveness is due to something other than sex differences in ER levels or function in the hippocampus.

Chronic corticosterone treatment induces parallel changes in N-methyl-D-aspartate receptor subunit messenger RNA levels and antagonist binding sites in the hippocampus.

Some of the effects of glucocorticoids on the function and neuronal plasticity of the hippocampus are mediated by N-methyl-D-aspartate receptor activation. We tested the hypothesis that chronic corticosterone administration increases N-methyl-D-aspartate receptor expression in the hippocampus of the rat. We used in situ hybridization histochemistry to measure the messenger RNA levels for the NR1, NR2A and NR2B subunits of the N-methyl-D-aspartate receptor and [3H]dizocilpine maleate (a non-competitive antagonist) binding to measure N-methyl-D-aspartate receptor density. Since corticosterone depresses circulating testosterone levels, we also examined whether the effects of corticosterone are mediated by or interact with the effects of testosterone. In the intact animal, corticosterone increased messenger RNA levels for NR2A and NR2B but not NR1 subunits of the N-methyl-D-aspartate receptor in all regions of the hippocampus. Testosterone had no significant effect on messenger RNA levels of any of the subunits. The subunit composition determines the functional and pharmacological properties of the N-methyl-D-aspartate receptor. We used ifenprodil inhibition of [3H]dizocilpine maleate binding, which has been used to distinguish NR2A- from NR2B-containing receptors, to determine whether corticosterone altered the proportion of high- and low-affinity sites for ifenprodil in parallel with the changes in subunit messenger RNA levels. Corticosterone increased the density of [3H]dizocilpine maleate binding sites without changing the dissociation constant for [3H]dizocilpine maleate or the proportion of high- and low-affinity sites for ifenprodil. These data suggest that the effects of corticosterone on hippocampal function are mediated, in part, by parallel increases in NR2A and NR2B subunit levels and the number of receptor channel binding sites.

Ovarian steroids and the brain: implications for cognition and aging.

Ovarian steroids have many effects on the brain throughout the lifespan, beginning during gestation and continuing into senescence. These hormones affect areas of the brain that are not primarily involved in reproduction, such as the basal forebrain, hippocampus, caudate putamen, midbrain raphe, and brainstem locus coeruleus. Here we discuss three effects of estrogens and progestins that are especially relevant to memory processes and identify hormonal alterations associated with aging and neurodegenerative diseases. First, estrogens and progestins regulate synaptogenesis in the CA1 region of the hippocampus during the 4- to 5-day estrous cycle of the female rat. Formation of new excitatory synapses is induced by estradiol and involves N-methyl-D-aspartate (NMDA) receptors, whereas synaptic downregulation involves intracellular progestin receptors. Second, there are developmentally programmed sex differences in the hippocampal structure that mat help explain why male and female rats use different strategies to solve spatial navigation problems. During the period of development when testosterone is elevated in the male, aromatase and estrogen receptors are transiently expressed in the hippocampus. Recent data on behavior and synapse induction strongly suggest that this pathway is involved in the masculinization or defeminization of hippocampal structure and function. Third, ovarian steroids have effects throughout the brain, including effects on brainstem and midbrain catecholaminergic neurons, midbrain serotonergic pathways, and the basal forebrain cholinergic system. Regulation of the serotonergic system appears to be linked to the presence of estrogen- and progestin-sensitive neurons in the midbrain raphe, whereas the ovarian steroid influence on cholinergic function involves induction of choline acetyltransferase and acetylcholinesterase according to a sexually dimorphic pattern. Because of these widespread influences on these various neuronal systems, it is not surprising that ovarian steroids produce measurable cognitive effects after ovariectomy and during aging.

Estradiol increases the sensitivity of hippocampal CA1 pyramidal cells to NMDA receptor-mediated synaptic input: correlation with dendritic spine density.

Previous studies have shown that estradiol induces new dendritic spines and synapses on hippocampal CA1 pyramidal cells. We have assessed the consequences of estradiol-induced dendritic spines on CA1 pyramidal cell intrinsic and synaptic electrophysiological properties. Hippocampal slices were prepared from ovariectomized rats treated with either estradiol or oil vehicle. CA1 pyramidal cells were recorded and injected with biocytin to visualize spines. The association of dendritic spine density and electrophysiological parameters for each cell was then tested using linear regression analysis. We found a negative relationship between spine density and input resistance; however, no other intrinsic property measured was significantly associated with dendritic spine density. Glutamate receptor autoradiography demonstrated an estradiol-induced increase in binding to NMDA, but not AMPA, receptors. We then used input/output (I/O) curves (EPSP slope vs stimulus intensity) to determine whether the sensitivity of CA1 pyramidal cells to synaptic input is correlated with dendritic spine density. Consistent with the lack of an estradiol effect on AMPA receptor binding, we observed no relationship between the slope of an I/O curve generated under standard recording conditions, in which the AMPA receptor dominates the EPSP, and spine density. However, recording the pharmacologically isolated NMDA receptor-mediated component of the EPSP revealed a significant correlation between I/O slope and spine density. These results indicate that, in parallel with estradiol-induced increases in spine/synapse density and NMDA receptor binding, estradiol treatment increases sensitivity of CA1 pyramidal cells to NMDA receptor-mediated synaptic input; further, sensitivity to NMDA receptor-mediated synaptic input is well correlated with dendritic spine density.

Aging of the female reproductive system: a window into brain aging.

The menopause marks the permanent end of fertility in women. It was once thought that the exhaustion of ovarian follicles was the single, most important explanation for the transition to the menopause. Over the past decade, this perception has gradually changed with the realization that there are multiple pacemakers of reproductive senescence. We will present evidence that lends credence to the hypothesis that the central nervous system is a critical pacemaker of reproductive aging and that changes at this level contribute to the timing of the menopause. Studies demonstrate that an increasing de-synchronization of the temporal order of neuroendocrine signals may contribute to the accelerated rate of follicular loss that occurs during middle age. We suggest that the dampening and destabilization of the precisely orchestrated ultradian, circadian, and infradian neural signals lead to miscommunication between the brain and the pituitary-ovarian axis. This constellation of hypothalamic-pituitary-ovarian events leads to the inexorable decline of regular cyclicity and heralds menopausal transition.